Translational lung cancer research最新文献

{"title":"Effect of laterality on the postoperative survival of non-small cell lung cancer patients undergoing pneumonectomy.","authors":"Zi-Ming Wang, Liang Guo, Yang Yang, Bo Tao, Wen-Qiang Zhang, Diego Gonzalez-Rivas, Jens-C Rueckert, Chee Yik Er, Calvin S H Ng, Moshe Lapidot, Gaetano Rocco, Mahmoud Ismail, Chen-Lu Yang, De-Ping Zhao","doi":"10.21037/tlcr-24-700","DOIUrl":"10.21037/tlcr-24-700","url":null,"abstract":"<p><strong>Background: </strong>Pneumonectomy is one of the important surgical methods for non-small cell lung cancer (NSCLC). This study evaluated the effects of laterality on the short- and long-term survival of NSCLC patients undergoing pneumonectomy.</p><p><strong>Methods: </strong>We reviewed the Surveillance, Epidemiology, and End Results database to retrieve the data of patients who underwent pneumonectomy for stage I-III NSCLC from 2004 to 2015. Propensity score matching (PSM) was used to reduce the selection bias. Logistic regression was used to analyze the correlation between laterality and mortality at 3, 6, and 9 months. The Kaplan-Meier curve was used to further assess the effect of laterality on overall survival (OS).</p><p><strong>Results: </strong>A total of 4,763 patients met the enrollment criteria [right-sided, 1,988 (41.7%); left-sided, 2,775 (58.3%)]. After PSM, 1,911 patients for each side were included in the further analysis. The first 6 months following pneumonectomy was the main period of death, with 32.0% (428/1,336) and 19.9% (250/1,258) of right- and left-sided deaths occurring during this period. The logistic regression analysis showed that right-sided pneumonectomy was an independent risk factor for 3- (P<0.001) and 6-month (P<0.001) mortality. However, laterality had no significant effect on postoperative death at 7-9 months (P=0.82). In the total cohort, right-sided patients had worse OS (P<0.001), but the subgroup survival analysis of patients with a follow-up period >6 months revealed that laterality had no statistically significant effect on OS (P=0.75).</p><p><strong>Conclusions: </strong>Right-sided pneumonectomy was associated with a higher perioperative mortality risk that lasted about 6 months. After that period, laterality was not observed to have a significant prognostic effect on the OS of patients undergoing pneumonectomy.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of lung cancer cell lines and tumorigenesis in mice from malignant pleural effusion in patients with lung cancer.","authors":"Nobuhiro Kanaji, Masanao Yokohira, Takuya Inoue, Naoki Watanabe, Hitoshi Mizoguchi, Yuta Komori, Kosuke Kawada, Norimitsu Kadowaki","doi":"10.21037/tlcr-24-143","DOIUrl":"10.21037/tlcr-24-143","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer was often diagnosed by malignant pleural effusion (MPE). Excessive MPE is generally discarded. The establishment of cell lines and the generation of cancer mouse models have the potential to be directly linked to personalized medicine. This study aimed to establish cell lines and generate mouse models using MPE.</p><p><strong>Methods: </strong>Cells derived from 5 mL of MPE were cultured in several conditions, including 100% MPE supernatant and Roswell Park Memorial Institute-1640 supplemented with 10% fetal bovine serum (FBS) or 10% MPE supernatant. When steady cell growth was observed, fewer cells were spread and the colonies were selected to establish the cell line. Cells derived from 10 mL of MPE were inoculated subcutaneously into non-obese diabetic-severe combined immunodeficiency (NOD-<i>scid</i>) and NOD.Cg-<i>Prkdc^scid Il2rg^tmlWjl</i> /SzJ (NSG) mice to assess tumorigenic potential.</p><p><strong>Results: </strong>MPEs were obtained from 28 lung cancer patients, 23 of whom had adenocarcinoma. Cell lines were established from 5 patients (18%). Tumorigenesis was observed in 6 of 28 cases (21%). However, in 7 cases, the mice (7 NSG and 1 NOD-<i>scid</i> mice) became progressively weaker, lost their hair, and died within 12 weeks without tumorigenesis. The appearance and pathological findings were consistent with graft-versus-host disease. Cell line establishment and tumorigenesis in mice were associated with a lower response to first-line therapy and poorer prognosis of patients.</p><p><strong>Conclusions: </strong>When MPEs were simply utilized, the cell line establishment rate was 18% and the engraftment rate in mice was 21%. The prognosis of patients who underwent cell line establishment and engraftment in mice was poor.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, prevalence, and survival of lung cancer in the United Kingdom from 2000-2021: a population-based cohort study.","authors":"George Corby, Nicola L Barclay, Eng Hooi Tan, Edward Burn, Antonella Delmestri, Talita Duarte-Salles, Asieh Golozar, Wai Yi Man, Ilona Tietzova, Daniel Prieto-Alhambra, Danielle Newby","doi":"10.21037/tlcr-24-241","DOIUrl":"10.21037/tlcr-24-241","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer-associated mortality worldwide. In the United Kingdom (UK), there has been a major reduction in smoking, the leading risk factor for lung cancer. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK. This study aims to describe lung cancer burden and trends in terms of incidence, prevalence, and survival from 2000-2021, using two UK primary care databases.</p><p><strong>Methods: </strong>We performed a population-based cohort study using the UK primary care Clinical Practice Research Datalink (CPRD) GOLD database, compared with CPRD Aurum. Participants aged 18+ years, with 1-year of prior data availability, were included. We estimated lung cancer incidence rates (IRs), period prevalence (PP), and survival at 1, 5 and 10 years after diagnosis using the Kaplan-Meier (KM) method.</p><p><strong>Results: </strong>Overall, 11,388,117 participants, with 45,563 lung cancer cases were studied. The IR of lung cancer was 52.0 [95% confidence interval (CI): 51.5 to 52.5] per 100,000 person-years, with incidence increasing from 2000 to 2021. Females aged over 50 years of age showed increases in incidence over the study period, ranging from increases of 8 to 123 per 100,000 person-years, with the greatest increase in females aged 80-89 years. Alternatively, for males, only cohorts aged over 80 years showed increases in incidence over the study period. The highest IR was observed in people aged 80-89 years. PP in 2021 was 0.18%, with the largest rise seen in participants aged over 60 years. Median survival post-diagnosis increased from 6.6 months in those diagnosed between 2000-2004 to 10.0 months between 2015-2019. Both short and long-term survival was higher in younger cohorts, with 82.7% 1-year survival in those aged 18-29 years, versus 24.2% in the age 90+ years cohort. Throughout the study period, survival was longer in females, with a larger increase in survival over time than in males.</p><p><strong>Conclusions: </strong>The incidence and prevalence of lung cancer diagnoses in the UK have increased, especially in female and older populations, with a small increase in median survival. This study will enable future comparisons of overall disease burden, so the overall impact may be seen.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.","authors":"Tingting Liu, Xueyuan Chen, Silang Mo, Ting Zhou, Wenjuan Ma, Gang Chen, Xiang Chen, Mengting Shi, Yuwen Yang, Yan Huang, Hongyun Zhao, Wenfeng Fang, Yunpeng Yang, Jing Li, Li Zhang, Yuanyuan Zhao","doi":"10.21037/tlcr-24-292","DOIUrl":"10.21037/tlcr-24-292","url":null,"abstract":"<p><strong>Background: </strong>Lung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC.</p><p><strong>Methods: </strong>Patients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored.</p><p><strong>Results: </strong>One hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3⁺ cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3⁺ (P=0.004), CD8⁺ (P=0.01), and CD68⁺ (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC.</p><p><strong>Conclusions: </strong>Our study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem-like exhausted CD8 T cells in pleural effusions predict improved survival in non-small cell lung cancer (NSCLC) and mesothelioma.","authors":"Linda Ye, Heeju Ryu, David Granadier, Long T Nguyen, Yannick Simoni, Ian Dick, Tina Firth, Ebony Rouse, Peter Chiang, Y C Gary Lee, Bruce W Robinson, Jenette Creaney, Evan W Newell, Alec J Redwood","doi":"10.21037/tlcr-24-284","DOIUrl":"10.21037/tlcr-24-284","url":null,"abstract":"<p><strong>Background: </strong>Anti-tumor CD8 T cells are important for immunity but can become 'exhausted' and hence ineffective. Tumor-infiltrating exhausted CD8⁺ T cells include less differentiated stem-like exhausted T (Tex^stem) cells and terminally exhausted T (Tex^term) cells. Both subsets have been proposed as prognostic biomarkers in cancer patients. In this study, we retrospectively investigated their prognostic significance in patients with metastatic non-small cell lung cancer (NSCLC) and validated our findings in a mesothelioma cohort.</p><p><strong>Methods: </strong>Pre-treatment malignant pleural effusions (PEs) from 43 NSCLC (41 non-squamous, 2 squamous) patients were analyzed by flow cytometry. The percentages of Tex^stem and Tex^term CD8 T cells were correlated with overall survival (OS) after adjusting for clinicopathological variables. Findings were validated using a mesothelioma cohort (n=49). Mass cytometry was performed on 16 pre-treatment PE samples from 5 mesothelioma and 3 NSCLC patients for T-cell phenotyping. Single-cell multi-omics analysis was performed on 4 pre-treatment PE samples from 2 NSCLC patients and 2 mesothelioma patients for analysis of the transcriptomic profiles, surface markers and T cell receptor (TCR) repertoire.</p><p><strong>Results: </strong>Higher frequency of Tex^stem was associated with significantly increased OS [median 9.9 <i>vs.</i> 3.4 months, hazard ratio (HR) 0.36, 95% CI: 0.16-0.79, P=0.01]. The frequency of Tex^term was not associated with OS. These findings were validated in the mesothelioma cohort (high <i>vs.</i> low Tex^stem, median OS 32.1 <i>vs.</i> 19.8 months, HR 0.31, 95% CI: 0.10-0.96, P=0.04). Detailed single-cell sequencing and mass cytometry profiling revealed that exhausted T cells from NSCLC expressed greater stem-likeness and less inhibitory markers than those from mesothelioma and that Tex^stem cells also contained 'bystander' virus-specific T cells.</p><p><strong>Conclusions: </strong>This study demonstrates that PE CD8 Tex^stem cell abundance is associated with better survival outcomes, and thus may be a useful prognostic biomarker.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM27 revealing by tumor educated platelet RNA-sequencing, as a potential biomarker for malignant ground-glass opacities diagnosis mediates glycolysis of non-small cell lung cancer cells partially through HOXM1.","authors":"Yan Hu, Chao Zeng, Jina Li, Siying Ren, Mengqi Shao, Weixuan Lei, Junqi Yi, Wei Han, Jieming Cao, Jian Zou, Quanming Fei, Zeyu Cheng, Wenliang Liu","doi":"10.21037/tlcr-24-157","DOIUrl":"10.21037/tlcr-24-157","url":null,"abstract":"<p><strong>Background: </strong>Efficient ground-glass opacities (GGOs) diagnosis is challenging. A diagnostic method distinguishing malignant from benign GGOs is warranted. In this study, we sought to construct a noninvasive method based on tumor educated platelet (TEP) RNA profiles for malignant GGOs diagnosis and explore the molecular mechanism of the potential biomarker for the first time.</p><p><strong>Methods: </strong>Based on TEP RNA-sequencing (TEP RNA-seq) in benign and malignant GGOs, a classification model was constructed using differentially expressed genes (DEGs) and was used to evaluate diagnostic performance. High-throughput quantitative polymerase chain reaction (HT-qPCR) verified 23 genes selected from the top 60 DEGs between benign and malignant GGOs. The correlation between 17 verified DEGs and 22 key glycolytic genes was analyzed. Tripartite motif-containing 27 (TRIM27) overexpressing and knockdown (KD) cell models were constructed using A549 and PC-9 cells, respectively in which cell growth, apoptosis, migration and invasion were evaluated. The protein levels of HK-1/2, PKM1/2, LDHA and GLUT1 were evaluated by western blot. Glycolysis was evaluated through adenosine triphosphate (ATP), reactive oxygen species (ROS), lactate acid (LD) production, glucose uptake, and lactate dehydrogenase (LDH) activity assays. RNA-seq was performed in loss-of TRIM27-KD PC-9 cells to clarify the downstream factors of TRIM27 which was verified using western blot and immunofluorescence double staining.</p><p><strong>Results: </strong>In 81 samples, the 1,647-DEG-based classification model exhibited area under the curve (AUC), sensitivity, and specificity values of 0.99 [95% confidence interval (CI): 0.972-1.000], 100%, and 91%, respectively, while the top 60-DEG-based classification model exhibited AUC, sensitivity, and specificity values of 0.986 (95% CI: 0.962-1.000), 98%, and 91%, respectively. TRIM27 achieved AUC of 0.87 in the diagnosis of malignant GGOs, with 83.93% sensitivity, 78.79% specificity, 81.15% accuracy, 77.05% positive predictive value (PPV) and 85.25% negative predictive value (NPV). TRIM27 was highly expressed in non-small cell lung cancer (NSCLC) cells, and accelerated cell migration and invasion. In addition, TRIM27 was found to promote glycolysis in NSCLC cells partially through HMOX1 which was negatively correlated with TRIM27.</p><p><strong>Conclusions: </strong>We constructed a novel TEP RNA-seq based classifier for malignant GGOs diagnosis. TRIM27, an important target discovered, could accelerate migration, invasion and regulate glycolysis partially through HMOX1 in NSCLC cells, thus providing scientific support for TRIM27 as a diagnostic biomarker for malignant GGO diagnosis.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALK-tyrosine kinase inhibitor intrinsic resistance due to <i>de novo</i> <i>MET</i>-amplification in metastatic <i>ALK</i>-rearranged non-small cell lung cancer effectively treated by alectinib-crizotinib combination-case report.","authors":"Edyta M Urbanska, Morten Grauslund, Siv M S Berger, Junia C Costa, Peter R Koffeldt, Jens B Sørensen, Eric Santoni-Rugiu","doi":"10.21037/tlcr-24-439","DOIUrl":"10.21037/tlcr-24-439","url":null,"abstract":"<p><strong>Background: </strong>Most patients with advanced anaplastic lymphoma kinase (<i>ALK</i>)-rearranged (<i>ALK</i>+) non-small cell lung cancer (NSCLC) experience prolonged response to second-generation (2G) ALK-tyrosine kinase inhibitors (TKIs). Herein, we present a case of metastatic <i>ALK</i>+ NSCLC rapidly progressing on first-line treatment due to <i>de novo</i> amplification of the mesenchymal-epithelial transition factor (<i>MET</i>) gene, which is a still elusive and underrecognized mechanism of primary resistance to ALK-TKIs.</p><p><strong>Case description: </strong>A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 (<i>EML4</i>)<i>-ALK</i> fusion variant 1 (<i>EML4-ALK</i> v.1) and <i>TP53</i> co-mutation, displayed only mixed response after three months and highly symptomatic progression after 6 months of first-line brigatinib treatment. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis on re-biopsies from a new liver metastasis revealed overexpression of MET receptor (3+ in 80% of tumor cells) and heterogeneously increased <i>MET</i> gene copy number (CN) in tumor cells, including 20% with <i>MET</i> clusters (corresponds to ≥15 gene copies, thus exact CN uncountable by FISH) and the other 80% with median <i>MET</i> CN of 8.3, both changes indicating high-level <i>MET-</i>amplification. DNA and RNA next-generation sequencing (NGS) displayed preserved <i>ALK</i> fusion and <i>TP53</i> co-mutation, but no additional genomic alterations, nor <i>MET-</i>amplification. Therefore, we retrospectively investigated the diagnostic biopsy from the primary tumor in the left lung with IHC and FISH revealing the presence of increased MET receptor expression (2+ in 100% of tumor cells) and <i>MET-</i>amplification (median <i>MET</i> CN of 6.1), which otherwise was not detected by NGS. Thus, given the well-documented efficacy of alectinib towards <i>EML4-ALK</i> v.1, combined second-line treatment with alectinib and the MET-TKI, crizotinib, was implemented resulting in very pronounced objective response, significantly improved quality of life, and no adverse events so far during the ongoing treatment (6 months).</p><p><strong>Conclusions: </strong>The combination of alectinib and crizotinib may be a feasible and effective treatment for <i>ALK</i>+ NSCLC with <i>de novo</i> <i>MET-</i>amplification. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of circulating proteins at diagnosis among patients with lung cancer: a comprehensive analysis by smoking status.","authors":"Xiaoshuang Feng, Hilary A Robbins, Anush Mukeriya, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Jolanta Lissowska, Miodrag Ognjanovic, Beata Swiatkowska, David Zaridze, Paul Brennan, Mattias Johansson, Mahdi Sheikh","doi":"10.21037/tlcr-24-242","DOIUrl":"10.21037/tlcr-24-242","url":null,"abstract":"<p><strong>Background: </strong>Improved prediction of prognosis among lung cancer patients could facilitate better clinical management. We aimed to study the prognostic significance of circulating proteins at the time of lung cancer diagnosis, among patients with and without smoking history.</p><p><strong>Methods: </strong>We measured 91 proteins using the Olink Immune-Oncology panel in plasma samples that were collected at diagnosis from 244 never smoking and 742 ever smoking patients with stage I-IIIA non-small cell lung cancer (NSCLC). Patients were recruited from nine centres in Russian Federation, Poland, Serbia, Czechia, and Romania, between 2007-2016 and were prospectively followed through 2020. We used multivariable Survey-weighted Cox models to assess the relationship between overall survival and levels of proteins by adjusting for smoking, age at diagnosis, sex, education, alcohol intake, histology, and stage.</p><p><strong>Results: </strong>The 5-year survival rate was higher among never than ever smoking patients (63.1% <i>vs.</i> 46.6%, P<0.001). In age- and sex-adjusted survival analysis, 23 proteins were nominally associated with overall survival, but after adjustment for potential confounders and correcting for multiple testing, none of the proteins showed a significant association with overall survival. In stratified analysis by smoking status, IL8 [hazard ratio (HR) per standard deviation (SD): 1.40, 95% confidence interval (CI): 1.18-1.65, P=1×10^-4] and hepatocyte growth factor (HGF) (HR: 1.45, 95% CI: 1.18-1.79, P=5×10^-4) were associated with survival among never smokers, but no protein was found associated with survival among ever smokers. Integrating proteins into the models with clinical risk factors did not improve the predictive performance of NSCLC prognosis [C-index of 0.63 (clinical) <i>vs.</i> 0.64 (clinical + proteins) for ever smokers, P=0.20; C-index of 0.68 (clinical) <i>vs.</i> 0.72 (clinical + proteins) for never smokers, P=0.28].</p><p><strong>Conclusions: </strong>We found limited evidence of a potential for circulating immune- and cancer-related protein markers in lung cancer prognosis. Whereas some specific proteins appear to be uniquely associated with lung cancer survival in never smokers.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced tumor targeting and penetration of fluorophores via iRGD peptide conjugation: a strategy for the precision targeting of lung cancer.","authors":"Yunlong Li, Chenmei Li, Jiamin Li, Dong Han, Gang Xu, Daolong Zhu, Huiming Cai, Yiqing Wang, Dong Wang","doi":"10.21037/tlcr-24-589","DOIUrl":"https://doi.org/10.21037/tlcr-24-589","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Accurate real-time tumor delineation is essential for achieving curative resection (R0 resection) during non-small cell lung cancer (NSCLC) surgery. The unique characteristics of lung tissue structure significantly challenge the use of video-assisted thoracoscopic surgery in the identification of lung nodules. This difficulty often results in an inability to discern the margins of lung nodules, necessitating either an expansion of the resection scope, or a transition to open surgery. Due to its high spatial resolution, ease of operation, and capacity for real-time observation, near-infrared fluorescence (NIRF) navigation in oncological surgery has emerged as a focal point of clinical research. Targeted NIRF probes, which accumulate preferentially in tumor tissues and are rapidly cleared from normal tissues, enhance diagnostic sensitivity and surgical outcomes. The imaging effect of the clinically approved NIRF probe indocyanine green (ICG) varies significantly from person to person. Therefore, we hope to develop a new generation of targeted NIRF probes targeting lung tumor-specific targets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;First, the peptide iRGD (sequence: CRGDKGPDC) fluorescent tracer was synthesized, and characterized through mass spectrometry (MS), proton nuclear magnetic resonance (&lt;sup&gt;1&lt;/sup&gt;H NMR), and high-performance liquid chromatography (HPLC). Fluorescence properties were tested subsequently. Safety was performed &lt;i&gt;in vitro&lt;/i&gt; using both human normal liver cells and human normal breast cells. Second, Metabolism and optimal imaging time were determined by tail vein injection of iRGD fluorescent tracer. Finally, Orthotopic and metastatic lung tumor models were used to evaluate the targeting properties of the iRGD fluorescent tracer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We successfully synthesized an iRGD fluorescent tracer specifically designed to target NSCLC. The molecular docking analyses indicated that this tracer has receptor affinity comparable to that of iRGD for αvβ3 integrin, with a purity ≥98%. Additionally, the tracer is highly soluble in water, and its excitation and emission wavelengths are 767 and 799 nm, respectively, positioning it within the near-infrared spectrum. The cellular assays confirmed the tracer's minimal cytotoxicity, underscoring its excellent biosafety profile. &lt;i&gt;In vivo&lt;/i&gt; studies further validated the tracer's capacity for specific NSCLC detection at the cellular level, alongside a prolonged imaging window of 6 days or more. Notably, the tracer demonstrated superior specificity in localizing very small lung nodules, which are otherwise clinically indiscernible, outperforming non-targeted ICG. Fluorescence intensity analyses across various organs revealed that the tracer is predominantly metabolized by the liver and kidneys, with excretion via bile and urine, and exhibits minimal toxicity to these organs as well as the lungs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The iRGD fluor","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research into overcoming drug resistance in lung cancer treatment using CRISPR-Cas9 technology: a narrative review.","authors":"Bin Liu, Ziyu Wang, Meng Gu, Jinghui Wang, Jinjing Tan","doi":"10.21037/tlcr-24-592","DOIUrl":"https://doi.org/10.21037/tlcr-24-592","url":null,"abstract":"<p><strong>Background and objective: </strong>Lung cancer remains a leading cause of cancer-related mortality globally, with drug resistance posing a significant challenge to effective treatment. The advent of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9) technology offers a novel and precise gene-editing technology for targeting and negating drug resistance mechanisms in lung cancer. This review summarizes the research progress in the use of CRISPR-Cas9 technology for investigating and managing drug resistance in lung cancer treatment.</p><p><strong>Methods: </strong>A literature search was conducted using the Web of Science and PubMed databases, with the following keywords: [CRISPR-Cas9], [lung cancer], [drug resistance], [gene editing], and [gene therapy]. The search was limited to articles published in English from 2002 to September 2023. From the search results, studies that utilized CRISPR-Cas9 technology in the context of lung cancer drug resistance were selected for further analysis and summarize.</p><p><strong>Key content and findings: </strong>CRISPR-Cas9 technology enables precise DNA-sequence editing, allowing for the targeted addition, deletion, or modification of genes. It has been applied to investigate drug resistance in lung cancer by focusing on key genes such as epidermal growth factor receptor (<i>EGFR</i>), Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>), tumor protein 53 (<i>TP53</i>), and B-cell lymphoma/leukemia-2 (<i>BCL2</i>), among others. The technology has shown potential in inhibiting tumor growth, repairing mutations, and enhancing the sensitivity of cancer cells to chemotherapy. Additionally, CRISPR-Cas9 has been used to identify novel key genes and molecular mechanisms contributing to drug resistance, offering new avenues for therapeutic intervention. The review also highlights the use of CRISPR-Cas9 in targeting immune escape mechanisms and the development of strategies to improve drug sensitivity.</p><p><strong>Conclusions: </strong>The CRISPR-Cas9 technology holds great promise for advancing lung cancer treatment, particularly in addressing drug resistance. The ability to precisely target and edit genes involved in resistance pathways offers a powerful tool for developing more effective and personalized therapies. While challenges remain in terms of delivery, safety, and ethical considerations, ongoing research and technological refinements are expected to further enhance the role of CRISPR-Cas9 in improving patient outcomes in lung cancer treatment.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}