Translational cancer research最新文献

{"title":"Feasibility and safety of transarterial chemoembolization in patients with liver cancer via the distal radial approach: a single-center retrospective cohort study.","authors":"Xinsen Wang, Lei Xian, Wenlei Zhang, Yang Xu, Delong Zhao, Xue Wang","doi":"10.21037/tcr-24-1231","DOIUrl":"https://doi.org/10.21037/tcr-24-1231","url":null,"abstract":"<p><strong>Background: </strong>The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety.</p><p><strong>Methods: </strong>We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture.</p><p><strong>Results: </strong>Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve.</p><p><strong>Conclusions: </strong>The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of breast MRI in evaluation of triple-negative breast cancer and fibroadenoma of less than 3 cm.","authors":"Zifan Wei, Xue Chen, Yiwen Yang, Ling Yang, Xinxing Ma","doi":"10.21037/tcr-24-498","DOIUrl":"https://doi.org/10.21037/tcr-24-498","url":null,"abstract":"<p><strong>Background: </strong>The majority of small-sized (<3 cm) triple-negative breast cancer (TNBC) exhibit smooth margins upon palpation and are often oval or rounded masses. Distinguishing these masses preoperatively from fibroadenomas (FAs) would be very meaningful for clinical practice. The aim of our study was to evaluate the magnetic resonance imaging (MRI) appearance of TNBC and differentiate it from FAs.</p><p><strong>Methods: </strong>In this retrospective single-center study, we included 37 patients with TNBCs and 36 patients with FAs who underwent breast MRI. We employed the χ² test and <i>t-</i>test to compare the differences in morphological features, dynamic contrast-enhanced MRI (DCE-MRI) parameters, and apparent diffusion coefficient (ADC) values between the two groups. Additionally, we constructed non-parametric receiver operating characteristic (ROC) curves using ADC values, with pathological results serving as the gold standard.</p><p><strong>Results: </strong>A total of 37 TNBC lesions and 39 FA lesions were included in the final analysis. TNBCs exhibited more frequent irregular shape, irregular margins, peritumoral edema, fast enhancement in the initial phase, rim enhancement, and time-signal intensity curve (TIC) type III compared to FAs (all P<0.05). Conversely, low-signal segregation in T2-weighted imaging (T2WI) and TIC type I were commonly found in FAs. The mean ADC value of TNBCs was significantly lower than that of FAs [(1.104±0.13)×10^-3 <i>vs</i>. (1.613±0.16)×10^-3 mm²/s, P<0.05]. The cutoff ADC for differentiating TNBCs from FAs was 1.239×10^-3 mm²/s, yielding an area under the curve (AUC) of 0.997, a sensitivity of 94.6%, and a specificity of 100%.</p><p><strong>Conclusions: </strong>The morphological presentation of MRI, internal enhancement features of the mass, TIC curves, and ADC values provide valuable differential diagnostic information for TNBC and FA masses with a maximum diameter of less than 3 cm.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of simvastatin in pancreatic neuroendocrine neoplasms: insights into cell cycle regulation and apoptosis.","authors":"Xiao-Ting Shi, Li-Jun Yan, Fei-Yu Lu, Mu-Jie Ye, Ping Yu, Yuan Zhong, Jin-Hao Chen, Chun-Hua Hu, Qi-Yun Tang","doi":"10.21037/tcr-24-363","DOIUrl":"https://doi.org/10.21037/tcr-24-363","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic neuroendocrine neoplasm (pNEN) poses significant challenges in clinical management due to their heterogeneity and limited treatment options. In this study, we investigated the potential of simvastatin (SIM) as an anti-tumor agent in pNEN.</p><p><strong>Methods: </strong>We conducted cell culture experiments using QGP-1 and BON-1 cell lines and assessed cell viability, proliferation, migration, and invasion following SIM treatment. To further validate our findings, we performed <i>in vivo</i> experiments using a mouse xenograft model. Additionally, we investigated the underlying molecular mechanisms by analyzing changes in cell cycle progression, apoptosis, and signaling pathways.</p><p><strong>Results: </strong>SIM treatment suppresses pNEN growth both <i>in vitro</i> and <i>in vivo</i>, and led to G1 phase arrest in QGP-1 cells. In contrast, SIM affected both the G1-S and G2-M phase transitions in the BON-1 cell line and induced apoptosis, indicating diverse mechanisms of action. Furthermore, SIM treatment resulted in decreased expression of mutant p53 (mutp53) in BON-1 cells, suggesting a potential therapeutic strategy targeting mutp53. Modulation of the MAPK pathway was also implicated in QGP-1 cells.</p><p><strong>Conclusions: </strong>Our study highlights SIM as a promising candidate for pNEN treatment by inducing cell cycle arrest or apoptosis, potentially through the p53 and MAPK pathways. Further research is warranted to fully elucidate SIM's mechanisms of action and evaluate its therapeutic potential in clinical settings.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics analysis of <i>SH2D4A</i> in glioblastoma multiforme to evaluate immune features and predict prognosis.","authors":"Tian Yang, Chujun Li, Duo Xu, Rui Quan, Lansheng Wang, Yanhong Ren, Zhengkui Zhang, Rutong Yu","doi":"10.21037/tcr-23-2000","DOIUrl":"https://doi.org/10.21037/tcr-23-2000","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer in adults. This study aimed to obtain data on immune cell infiltration based on public datasets and to examine the prognostic significance of SH2 domain containing 4A (<i>SH2D4A</i>) for GBM.</p><p><strong>Methods: </strong><i>SH2D4A</i> expression in GBM was analyzed using a Tumor Immunity Estimation Resource (TIMER) 2.0 dataset, and a gene expression profile interaction analysis (GEPIA), and the results were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The Chinese Glioma Genome Atlas (CGGA) dataset was used to assess the effect of <i>SH2D4A</i> on GBM patient survival. The <i>SH2D4A</i> co-expression network of the LinkedOmics dataset and GeneMANIA dataset was also investigated. Least absolute shrinkage and selection operator (LASSO) regression models and a nomogram were constructed to assess the prognosis of GBM patients. A Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset to find functional differences. The relationship between <i>SH2D4A</i> expression and tumor-infiltrating immune cells was analyzed using xCELL, the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, and the TIMER dataset.</p><p><strong>Results: </strong>We discovered that <i>SH2D4A</i> expression was upregulated in GBM patients, and elevated SH2D4A expression was also substantially correlated with tumor grade. The survival curve analysis and multivariate Cox regression analysis showed that high <i>SH2D4A</i> expression was a significant independent predictor of poor overall survival (OS) in GBM patients. The immunoassay results suggested that altered <i>SH2D4A</i> expression may affect the immune infiltration of GBM tissues and thus the survival outcomes of GBM patients.</p><p><strong>Conclusions: </strong>In addition to being a possible prognostic marker and therapeutic target for GBM, <i>SH2D4A</i> may also accelerate the progression of GBM.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tumor-derived exosomal gene signature predicts prognosis in patients with pancreatic cancer.","authors":"Yang Wang, Chao Liang, Xinbo Liu, Shu-Qun Cheng","doi":"10.21037/tcr-23-2354","DOIUrl":"https://doi.org/10.21037/tcr-23-2354","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a devastating disease with poor prognosis. Accumulating evidence has shown that exosomes and their cargo have the potential to mediate the progression of pancreatic cancer and are promising non-invasive biomarkers for the early detection and prognosis of this malignancy. This study aimed to construct a gene signature from tumor-derived exosomes with high prognostic capacity for pancreatic cancer using bioinformatics analysis.</p><p><strong>Methods: </strong>Gene expression data of solid pancreatic cancer tumors and blood-derived exosome tissues were downloaded from The Cancer Genome Atlas (TCGA) and ExoRBase 2.0. Overlapping differentially expressed genes (DEGs) in the two datasets were analyzed, followed by functional enrichment analysis, protein-protein interaction networks, and weighted gene co-expression network analysis (WGCNA). Using the least absolute shrinkage and selection operator (LASSO) regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was constructed based on the TCGA dataset, which was validated by an external validation dataset, GSE62452. The prognostic power of this gene signature and its relationship with various pathways and immune cell infiltration were analyzed.</p><p><strong>Results: </strong>A total of 166 overlapping DEGs were identified from the two datasets, which were markedly enriched in functions and pathways associated with the cell cycle. Two key modules and corresponding 70 exosomal DEGs were identified using WGCNA. Using LASSO Cox regression of prognosis-related exosomal DEGs, a tumor-derived exosomal gene signature was built using six exosomal DEGs (<i>ARNTL2</i>, <i>FHL2</i>, <i>KRT19</i>, <i>MMP1</i>, <i>CDCA5</i>, and <i>KIF11</i>), which showed high predictive performance for prognosis in both the training and validation datasets. In addition, this prognostic signature is associated with the differential activation of several pathways, such as the cell cycle, and the infiltration of some immune cells, such as Tregs and CD8+ T cells.</p><p><strong>Conclusions: </strong>This study established a six-exosome gene signature that can accurately predict the prognosis of pancreatic cancer.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic prediction of miR-320a as a potential negative regulator of CDGSH iron-sulfur domain 2 (<i>CISD2</i>), involved in lung adenocarcinoma bone metastasis via MYC activation, and associated with tumor immune infiltration.","authors":"Xiaoxi Zhao, Lei Li, Yancheng Li, Yanxiao Liu, Hua Wang, Nika Samadzadeh Tabrizi, Zhou Ye, Ziru Zhao","doi":"10.21037/tcr-24-1188","DOIUrl":"https://doi.org/10.21037/tcr-24-1188","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Ferroptosis, a form of regulated cell death associated with iron-dependent lipid peroxidation, plays a role in cancer progression. However, the specific mechanisms of ferroptosis in lung adenocarcinoma (LUAD) bone metastasis (BM) remain unclear. Using bioinformatics analysis, this study sought to identify the ferroptosis-associated genes involved in BM in LUAD, thus providing potential novel targets for the treatment of BM in LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The RNA expression dataset GSE10799 was acquired from the Gene Expression Omnibus (GEO) database, and intersected with the ferroptosis dataset to identify ferroptosis-related differentially expressed genes (DEGs). The expression of candidate genes and their correlation with the prognosis of LUAD patients were validated in The Cancer Genome Atlas (TCGA) database. A protein gene interaction network was constructed using GeneMania and Retrieval of Interacting Genes/Proteins (STRING) databases. The association between the candidate genes and immune cells was assessed via TCGA and Tumor IMmune Estimation Resource (TIMER) databases. The potential mechanisms were elucidated by a gene set enrichment analysis (GSEA). The relevant microRNAs (miRNAs or miRs) that bind to the 3'untranslated region (3'UTR) end of candidate genes' mRNA was explored using the TargetScan database. The expression of these candidate miRNAs in LUAD was validated and the correlation between candidate miRNAs and candidate mRNAs was tested using the TCGA database. Finally, the clinical data of 40 LUAD patients were retrospectively analyzed to evaluate the clinical value of candidate gene expression for LUAD BM patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In this research, 15 ferroptosis-related DEGs in LUAD BM were identified. TCGA database analysis indicated that patients with low levels of CDGSH iron-sulfur domain 2 (&lt;i&gt;CISD2&lt;/i&gt;) in LUAD had better disease-specific survival (DSS), overall survival (OS), and a better progression-free interval (PFI) than those with high levels of &lt;i&gt;CISD2&lt;/i&gt;. The TIMER database results show that the expression of &lt;i&gt;CISD2&lt;/i&gt; is correlated with the infiltration levels of various immune cells. The GSEA indicated that &lt;i&gt;CISD2&lt;/i&gt; might influence biological activity in LUAD by participating in cell-cycle regulation, mitochondrial translation, DNA damage repair, c-&lt;i&gt;Myc&lt;/i&gt; (&lt;i&gt;MYC&lt;/i&gt;) activation, and the P53 signaling pathway. Through the combined analysis of the TargetScan and TCGA databases, hsa-miR-320a was identified as the optimal upstream regulatory miRNA. The immunohistochemistry data indicated that the positive CISD2 expression rates and immunohistochemistry scores of the patients with BM were significantly higher than those of the patients without BM (P&lt;0.05). The high expression of CISD2 is a significant risk factor for BM in LUAD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The downregulation of &lt;i&gt;CISD2&lt;/i&gt; expression may extend DSS, OS, and the PFI of LUAD ","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expression of programmed cell death ligand 1 (PD-L1) involves in the clinicopathologic characteristics and prognostic implications of testicular germ cell tumor (TGCT): a systematic review and meta-analysis.","authors":"Peifeng Li, Yuwei Zhong, Miaotao Zhang, Yonghong Zheng, Wei Peng","doi":"10.21037/tcr-23-2302","DOIUrl":"https://doi.org/10.21037/tcr-23-2302","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Testicular germ cell tumor (TGCT) is a type of tumor with relatively lower incidence but being more prevalent in young men. The expression of programmed cell death ligand 1 (PD-L1) serves as a potential biomarker for predicting the survival outcomes of other tumors. Some studies discovered higher prevalence of PD-L1 in TGCT patients who achieved favorable treatment outcomes, while other studies showed lower or absent expression of PD-L1 in TGCT with the better prognosis as well. Therefore, in order to address this controversy and clarify the association between the expression of PD-L1 and pathological features and prognosis of TGCT, this meta-analysis was conducted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A comprehensive literature search was performed using following search terms: \"testis\", \"testicle\", \"testicular\", \"cancer\", \"carcinoma\", \"tumor\", \"neoplasm\", \"programmed cell death ligand 1\", \"programmed death ligand 1\", \"PD-L1\", \"PDL1\", \"B7 homolog 1\", \"B7-H1\", \"B7H1\" and \"CD274\". Relevant studies were retrieved according to the inclusion criteria from reputable databases including PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). These studies investigated the expression of PD-L1 in both tumor cells and tumor infiltrating immune cells (TIICs) in TGCT. The overall proportion of PD-L1 positivity was assessed using R programming. Pooled hazard ratio (HR) and odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using Revman software to evaluate the involvement of PD-L1 expression in TGCT. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality assessment of included studies. Sensitivity analysis and publication bias evaluation were subsequently performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of eight eligible studies compromising 1,589 patients diagnosed with TGCT were finally included in this study. PD-L1 positivity was detected in 31% and 41% of TGCT patients' tumor cells and TIICs, respectively. The pooled data demonstrated a significant association between elevated PD-L1 expression levels in TIICs and a favorable prognosis characterized by the reduced disease progression and relapse events (HR =0.21, 95% CI: 0.13-0.33). Furthermore, PD-L1&lt;sup&gt;+&lt;/sup&gt; TIICs exhibited higher prevalence rates in seminoma (OR =2.11, 95% CI: 1.57-2.84) and embryonal carcinoma (OR =6.23, 95% CI: 2.42-16.02) patients. Notably, PD-L1 expression in TIICs displayed a tendency to increase in TGCT patients with lower stages or without lymph node metastasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;PD-L1 expression was observed in choriocarcinoma tumor cells, while yolk sac tumor and teratoma tumor cells exhibited lower or absent expression of PD-L1. Conversely, PD-L1 expression in TIICs was associated with seminoma and embryonal carcinoma, which was more commonly observed in TGCT patients with lower stages and better prognosis, thereby providing a theoretical foun","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying epithelial-mesenchymal transition-related genes as prognostic biomarkers and therapeutic targets of hepatocellular carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.","authors":"Chen Chen, Shunyi Wang, Yuhong Tang, Huanxiang Liu, Daoyuan Tu, Bingbing Su, Rui Peng, Shengjie Jin, Guoqing Jiang, Jun Cao, Chi Zhang, Dousheng Bai","doi":"10.21037/tcr-24-521","DOIUrl":"https://doi.org/10.21037/tcr-24-521","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Patients with advanced HCC tend to have poor prognoses and shortened survival. Recently, data from bulk RNA sequencing have been employed to discover prognostic markers for various cancers. However, they fall short in precisely identifying core molecular and cellular activities within tumor cells. In our present study, we combined bulk-RNA sequencing (bulk RNA-seq) data with single-cell RNA sequencing (scRNA-seq) to develop a prognostic model for HCC. The goal of our research is to uncover new biomarkers and enhance the accuracy of HCC prognosis prediction.</p><p><strong>Methods: </strong>Integrating single-cell sequencing data with transcriptomics were used to identify epithelial-mesenchymal transition (EMT)-related genes (ERGs) implicated in HCC progression and their clinical significance was elucidated. Utilizing marker genes derived from core cells and ERGs, we constructed a prognostic model using univariate Cox analysis, exploring a multitude of algorithmic combinations, and further refining it through multivariate Cox analysis. Additionally, we conducted an in-depth investigation into the disparities in clinicopathological features, immune microenvironment composition, immune checkpoint expression, and chemotherapeutic drug sensitivity profiles between high- and low-risk patient cohorts.</p><p><strong>Results: </strong>We developed a prognostic model predicated on the expression profiles of eight signature genes, namely <i>HSP90AA1</i>, <i>CIRBP</i>, <i>CCR7</i>, <i>S100A9</i>, <i>ADAM17</i>, <i>ENG</i>, <i>PGF</i>, and <i>INPP4B</i>, aiming at predicting overall survival (OS) outcomes. Notably, patients classified with high-risk scores exhibited a propensity towards diminished OS rates, heightened frequencies of stage III-IV disease, increased tumor mutational burden (TMB), augmented immune cell infiltration, and diminished responsiveness to immunotherapeutic interventions.</p><p><strong>Conclusions: </strong>This study presented a novel prognostic model for predicting the survival of HCC patients by integrating scRNA-seq and bulk RNA-seq data. The risk score emerges as a promising independent prognostic factor, showing a correlation with the immune microenvironment and clinicopathological features. It provided new clinical tools for predicting prognosis and aided future research into the pathogenesis of HCC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special tissue microbiota such as Cyanobacteria are associated with the immune microenvironment of lung adenocarcinoma.","authors":"Shuqi Shen, Sijia Yu, Da Yao, Hao Wu, Youhui Qian","doi":"10.21037/tcr-24-107","DOIUrl":"https://doi.org/10.21037/tcr-24-107","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading prevalent form of human cancer and has the highest mortality rate among all cancer types. The role and potential mechanism of the lung microbiome in lung cancer is still unknown. This study aims to investigate the microbiomes of lung cancer patients possessing different levels of infiltrated CD8⁺ T cells and programmed cell death-1 (PD-1) receptors, and further assess the correlation between specific microbes and the immune environment of lung tumor.</p><p><strong>Methods: </strong>We analyzed the microbiomes of lung cancer tissues from patients with different levels of infiltrated CD8⁺ T cells and PD-1 expression using 16S rRNA gene sequencing. The relative abundance of dominant phyla and genera was compared, and the correlation between microbial composition and immune markers was explored.</p><p><strong>Results: </strong>Our results showed that lung cancer tissues displayed similar microbiome profiles, including Proteobacteria, Bacteroidetes, and Actinobacteria as the dominant phyla; and <i>Chryseobacterium, Triticum aestivum</i> (bread wheat), and <i>Acinetobacter</i> as the dominant genera. We found that the relative abundance of <i>Chryseobacterium</i> was positively correlated with CD8⁺ T cell infiltration and the level of PD-1 expression, while the relative abundance of <i>Acinetobacter</i> was negatively associated with the PD-1 level. In addition, higher beta diversity was identified in samples with low CD8⁺ T cell infiltration, but no significant correlation between beta diversity and PD-1 expression was observed. Furthermore, the relative abundance of Cyanobacteria was significantly higher in both the CD8 high and PD-1 high groups.</p><p><strong>Conclusions: </strong>Our study indicated that the lung microbiota played an indispensable role in the CD8⁺ T cell-mediated tumor immune response. These findings shed light on valuable insights into the intricate interplay between the lung microbiome and the immune system in the progression of lung cancer, offing potential therapeutic strategies targeting the lung microbiome.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GGT5 as a promising prognostic biomarker and its effects on tumor cell progression in gastric cancer.","authors":"Wenchao Chen, Fanfan Yang, Hao Shen, Jia Xu, Jin Chen, Zhezhong Zhang, Jian Xu, Bin Xu","doi":"10.21037/tcr-23-2222","DOIUrl":"https://doi.org/10.21037/tcr-23-2222","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a gastric malignant tumor with over 1 million new cases globally each year. There are many diagnostic methods for GC, but due to the hidden early symptoms of GC, early GC is easy to be missed and misdiagnosed, which affects the follow-up treatment of patients. The early and accurate diagnosis of GC is of great significance for the treatment and survival of GC patients. Our laboratory study found that gamma-glutamyl transferase (GGT) was highly expressed in GC patients, but the mechanism of GGT family genes in the occurrence and development of GC remained to be further studied. Therefore, this study aimed to explore the mechanism of GGT family functional gene GGT5 regulating the proliferation and migration of GC cells, and provide a possible new biomarker for the early diagnosis of GC.</p><p><strong>Methods: </strong>The value of serum GGT in GC patients was first statistically analyzed. Then, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the mRNA expression of GGT5 in GC, and its clinical relationship and function. Furthermore, expression of GGT5 was reduced by lentivirus RNA interference and verified by polymerase chain reaction (PCR), Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation after GGT5 knockdown. Scratch and Transwell assays were applied to observe cell migration after knockdown of GGT5. Finally, Western blot assays were observed to demonstrate PI3K/AKT-MAPK and MMPs expression levels after knockdown of GGT5.</p><p><strong>Results: </strong>Serum GGT was expressed at a high level in GC patients. GGT5 was highly expressed in GC tissues, and was associated with poor prognosis and clinical stage of GC. GGT5 might be involved in the regulation of vascular development and angiogenesis, as well as in the mechanisms of cell motility and migration, and it was positively correlated with the PI3K/AKT pathway. The proliferation and migration capacity of GC cells was dampened by downregulation of GGT5. GGT5 mediated proliferation and migration of GC cells by directly targeting PI3K/AKT-MAPK-MMPs pathways.</p><p><strong>Conclusions: </strong>Low expression of GGT5 reduced proliferation and migration in GC cells by modulating the PI3K/AKT-MAPK-MMPs pathway, and GGT5 might be a new target for GC.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}