Journal of the National Cancer Center最新文献

{"title":"Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status: 5-year follow-up of a prospective cohort study.","authors":"Xun Tian, Danhui Weng, Ye Chen, Yi Wang, Xiao Li, Xin Wang, Chen Cao, Danni Gong, Zhen Zeng, Qiongyan Wu, Xueqian Wang, Peng Wu, Lu Fan, Qinghua Zhang, Hui Wang, Zheng Hu, Xiaodong Cheng, Ding Ma","doi":"10.1016/j.jncc.2024.08.001","DOIUrl":"10.1016/j.jncc.2024.08.001","url":null,"abstract":"<p><strong>Objective: </strong>We investigated the relation between man papillomavirus (HPV) integration status and the immediate risk of cervical intraepithelial neoplasia (CIN), as well as the triage strategy based on HPV integration test.</p><p><strong>Methods: </strong>4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective, population-based, clinical observational study to evaluate the triage performance of HPV integration. Cervical exfoliated cells were collected for HPV testing and cytologic test. If high-risk HPV was positive, HPV integration test was performed at baseline, 2-year and 5-year follow-up.</p><p><strong>Results: </strong>At baseline, HPV integration was positively correlated with the severity of cervical pathology, ranging from 5.0% (15/301) in normal diagnosis, 6.9% (4/58) in CIN1, 31.0% (9/29) in CIN2, 70% (14/20) in CIN3, and 100% (2/2) in cervical cancer (<i>P</i> < 0.001). Compared with cytology, HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+, higher specificity (92.8% [90.2%-95.4%] vs. 75.5% [71.2%-79.8%], <i>P</i> < 0.001) and higher positive predictive value (36.4% [22.1%-50.6%] vs. 15.2% [8.5%-21.8%], <i>P</i> < 0.001). HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy (10.7% [44/410] vs. 27.3% [112/410], <i>P</i> < 0.001). The HPV integration-negative group exhibited the lowest immediate risk for CIN3+ (1.6%) and accounted for the largest proportion of the total population (89.3%), when compared with the normal cytology group (risk, 1.7%; proportion, 72.7%).</p><p><strong>Conclusion: </strong>As a key molecular basis for the development of cervical cancer, HPV integration might be a promising triage strategy for HPV-positive patients.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"311-317"},"PeriodicalIF":7.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoimmunology in bone malignancies: a symphony with evil.","authors":"Churui Song, Tie Tong, Biqi Dai, Yue Zhu, Elina Chen, Min Zhang, Weijie Zhang","doi":"10.1016/j.jncc.2024.09.001","DOIUrl":"10.1016/j.jncc.2024.09.001","url":null,"abstract":"<p><p>Bone marrow is pivotal for normal hematopoiesis and immune responses, yet it is often compromised by malignancies. The bone microenvironment (BME), composed of bone and immune cells, maintains skeletal integrity and blood production. The emergence of primary or metastatic tumors in the skeletal system results in severe complications and contributes significantly to cancer-related mortality. These tumors set off a series of interactions among cancer, bone, and immune cells, and disrupt the BME locally or distantly. However, the drivers, participants, and underlying molecules of these interactions are not fully understood. This review explores the crosstalk between bone metabolism and immune responses, synthesizing current knowledge on the intersection of cancer and osteoimmune biology. It outlines how bone marrow immune cells can either facilitate or hinder tumor progression by interacting with bone cells and pinpoints the molecules responsible for immunosuppression within bone tumors. Moreover, it discusses how primary tumors remotely alter the BME, leading to systemic immune suppression in cancer patients. This knowledge provides critical rationales for emerging immunotherapies in the treatment of bone-related tumors. Taken together, by summarizing the intricate relationship between tumor cells and the BME, this review aims to deepen the understanding of the diversity, complexity, and dynamics at play during bone tumor progression. Ultimately, it highlights the potential of targeting bone-tumor interactions to correct aberrant immune functions, thereby inhibiting tumor growth and metastasis.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"354-368"},"PeriodicalIF":7.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disseminated tumor cells in bone marrow as predictive classifiers for small cell lung cancer patients.","authors":"Ying Wang, Jingying Nong, Baohua Lu, Yuan Gao, Mingming Hu, Cen Chen, Lina Zhang, Jinjing Tan, Xiaomei Yang, Peter Ping Lin, Xingsheng Hu, Tongmei Zhang","doi":"10.1016/j.jncc.2024.07.003","DOIUrl":"10.1016/j.jncc.2024.07.003","url":null,"abstract":"<p><strong>Background: </strong>Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Aneuploid CD31^- disseminated tumor cells (DTCs) and CD31⁺ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical significance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients.</p><p><strong>Methods: </strong>Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells.</p><p><strong>Results: </strong>DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis revealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs (<i>P</i> < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes (<i>P</i> = 0.046 and <i>P</i> = 0.048). Patients with EpCAM⁺ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, <i>P</i> = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM^- DTCs (<i>P</i> = 0.028 and <i>P</i> = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mutations with pre-treatment CTCs compared with post-treatment CTCs.</p><p><strong>Conclusions: </strong>Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"335-345"},"PeriodicalIF":7.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.","authors":"Aimin Jiang, Ying Liu, Ziwei He, Wenqiang Liu, Qiwei Yang, Yu Fang, Baohua Zhu, Xiaofeng Wu, Huamao Ye, Bicheng Ye, Shunxiang Gao, Le Qu, Wenhao Xu, Peng Luo, Linhui Wang","doi":"10.1016/j.jncc.2024.07.002","DOIUrl":"10.1016/j.jncc.2024.07.002","url":null,"abstract":"<p><strong>Background: </strong>Tumor-derived exosomes are involved in tumor progression and immune invasion and might function as promising noninvasive approaches for clinical management. However, there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma (ccRCC).</p><p><strong>Methods: </strong>The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC patients were correspondingly deregulated in ccRCC tissues. We adopted a two-step strategy, including Lasso and bootstrapping, to construct a novel risk stratification system termed the TDERS (Tumor-Derived Exosome-Related Risk Score). During the testing and validation phases, we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS. In addition, enrichment analysis, immune infiltration signatures, mutation landscape and therapy sensitivity between the high and low TDERS groups were compared. Finally, the impact of TDERS on the tumor microenvironment (TME) was also analysed in our single-cell datasets.</p><p><strong>Results: </strong>TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC. TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor (ICI) response across all ccRCC cohorts and other pathological types, since the average area under the curve (AUC) to predict 5-year overall survival (OS) was larger than 0.8 across the four cohorts. Patients in the TDERS high group were resistant to ICIs, while mercaptopurine might function as a promising agent for those patients. Patients with a high TDERS were characterized by coagulation and hypoxia, which induced hampered tumor antigen presentation and relative resistance to ICIs. In addition, single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited. Finally, PLOD2, which is highly expressed in fibro- and epi‑tissue, could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC <i>in vitro</i>.</p><p><strong>Conclusion: </strong>As a novel, non-invasive, and repeatable monitoring tool, the TDERS could work as a robust risk stratification system for patients with ccRCC and precisely inform treatment decisions about ICI therapy.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"382-394"},"PeriodicalIF":7.6,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer survival statistics in China 2019–2021: a multicenter, population-based study","authors":"Hongmei Zeng ,&nbsp;Rongshou Zheng ,&nbsp;Kexin Sun ,&nbsp;Maigeng Zhou ,&nbsp;Shaoming Wang ,&nbsp;Li Li ,&nbsp;Ru Chen ,&nbsp;Bingfeng Han ,&nbsp;Meicen Liu ,&nbsp;Jinhui Zhou ,&nbsp;Mengyuan Xu ,&nbsp;Lijun Wang ,&nbsp;Peng Yin ,&nbsp;Baohua Wang ,&nbsp;Jinling You ,&nbsp;Jing Wu ,&nbsp;Wenqiang Wei ,&nbsp;Jie He","doi":"10.1016/j.jncc.2024.06.005","DOIUrl":"10.1016/j.jncc.2024.06.005","url":null,"abstract":"<div><h3>Background</h3><p>A milestone goal of the Healthy China Program (2019–2030) is to achieve 5-year cancer survival at 43.3% for all cancers combined by 2022. To assess the progress towards this target, we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021.</p></div><div><h3>Methods</h3><p>We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China, and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008–2019, with follow-up data on vital status available until December 2021. We estimated the age-standardized 5-year relative survival overall and by site, age group, and period of diagnosis using the International Cancer Survival Standard Weights, and quantified the survival changes to assess the progress in cancer control.</p></div><div><h3>Results</h3><p>In 2019–2021, the age-standardized 5-year relative survival for all cancers combined was 43.7% (95% confidence interval [CI], 43.6–43.7). The 5-year relative survival varied by cancer type, ranging from 8.5% (95% CI, 8.2–8.7) for pancreatic cancer to 92.9% (95% CI, 92.4–93.3) for thyroid cancer. Eight cancers had 5-year survival of over 60%, including cancers of the thyroid, breast, testis, bladder, prostate, kidney, uterus, and cervix. The 5-year relative survival was generally lower in males than in females. From 2008 to 2021, we observed significant survival improvements for cancers of the lung, prostate, bone, uterus, breast, cervix, nasopharynx, larynx, and bladder. The most significant improvement was in lung cancer.</p></div><div><h3>Conclusions</h3><p>Progress in cancer control was evident in China. This highlights the importance of a comprehensive approach to control and prevent cancer.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 203-213"},"PeriodicalIF":7.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000498/pdfft?md5=ba2f3e91467cd2db70ca6f11e93b38c3&pid=1-s2.0-S2667005424000498-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses","authors":"Chenyu Luo ,&nbsp;Jiahui Luo ,&nbsp;Yuhan Zhang ,&nbsp;Bin Lu ,&nbsp;Na Li ,&nbsp;Yueyang Zhou ,&nbsp;Shuohua Chen ,&nbsp;Shouling Wu ,&nbsp;Qingsong Zhang ,&nbsp;Min Dai ,&nbsp;Hongda Chen","doi":"10.1016/j.jncc.2024.04.006","DOIUrl":"10.1016/j.jncc.2024.04.006","url":null,"abstract":"<div><h3>Background</h3><p>The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated.</p></div><div><h3>Methods</h3><p>This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations.</p></div><div><h3>Results</h3><p>Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01–1.21, <em>P</em>-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01–1.51, <em>P</em>-trend = 0.036). Elevated glucose (&gt;7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07–2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02–1.27) in the UK Biobank cohort (<em>P-</em>heterogeneity = 0.014). Elevated glucose (&gt;7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04–1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC.</p></div><div><h3>Conclusions</h3><p>This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 241-248"},"PeriodicalIF":7.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000486/pdfft?md5=972b697a869f545991a79c7ca79d5b77&pid=1-s2.0-S2667005424000486-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and application of a three-dimensional vascular variation-based nephrometry scoring system for completely endophytic renal tumors.","authors":"Aihetaimujiang Anwaier, Xiangxian Che, Lei Shi, Xi Tian, Shiqi Ye, Wenhao Xu, Yu Zhu, Hailiang Zhang, Dingwei Ye","doi":"10.1016/j.jncc.2024.06.001","DOIUrl":"10.1016/j.jncc.2024.06.001","url":null,"abstract":"<p><strong>Background: </strong>Completely endophytic renal tumors (CERT) pose significant challenges due to their anatomical complexity and loss of visual clues about tumor location. A facile scoring model based on three-dimensional (3D) reconstructed images will assist in better assessing tumor location and vascular variations.</p><p><strong>Methods: </strong>In this retrospective study, 80 patients diagnosed with CERT were included. Forty cases underwent preoperative assessment using 3D reconstructed imaging (3D-Cohort), while the remaining 40 cases were assessed using two-dimensional imaging (2D-Cohort). Vascular variations were evaluated by ascertaining the presence of renal arteries > 1, prehilar branching arteries, and arteries anterior to veins. The proposed scoring system, termed RAL, encompassed three critical components: (R)adius (maximal tumor diameter in cm), (A)rtery (occurrence of arterial variations), and (L)ocation relative to the polar line. Comparison of the RAL scoring system was made with established nephrometry scoring systems.</p><p><strong>Results: </strong>A total of 48 (60%) patients exhibited at least one vascular variation. In the 2D-Cohort, patients with vascular variations experienced significantly prolonged operation time, increased bleeding volume, and extended warm ischemia time compared with those without vascular variations. Conversely, the presence of vascular variations did not significantly affect operative parameters in the 3D-Cohort. Furthermore, the 2D-Cohort demonstrated a notable decline in both short- and long-term estimated glomerular filtration rate (eGFR) changes compared with the 3D-Cohort, a trend consistent across patients with warm ischemia time ≥ 25 min and those with vascular variations. Notably, the 2D-Cohort exhibited a larger margin of normal renal tissue compared with the 3D-Cohort. Elevated RAL scores correlated with larger tumor size, prolonged operation time, extended warm ischemia time, and substantial postoperative eGFR decrease. The RAL scoring system displayed superior predictive capabilities in assessing postoperative eGFR changes compared with conventional nephrometry scoring systems.</p><p><strong>Conclusions: </strong>Our proposed 3D vascular variation-based nephrometry scoring system offers heightened proficiency in preoperative assessment, precise prediction of surgical complexity, and more accurate evaluation of postoperative renal function in CERT patients.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"346-353"},"PeriodicalIF":7.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological features of EGFR-mutant non-small cell lung cancer and clinical practice: a narrative review.","authors":"Yi Dong, Liaqat Khan, Yi Yao","doi":"10.1016/j.jncc.2024.06.004","DOIUrl":"10.1016/j.jncc.2024.06.004","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer (NSCLC). However, targeted therapy remains the preferred treatment for advanced driver-positive NSCLC, including cases with epidermal growth factor receptor (EGFR) mutations. Considering the variability in EGFR-mutant NSCLC, including expression levels of programmed cell death ligand 1 (PD-L1), tumor mutation burden (TMB), and other immunological features, the application of immunotherapy in this group is still a subject of investigation. Therefore, we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC, as well as the current clinical application of immunotherapy in the EGFR-mutant population, to provide a reference for future research.</p>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 4","pages":"289-298"},"PeriodicalIF":7.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DCS, a novel classifier system based on disulfidptosis reveals tumor microenvironment heterogeneity and guides frontline therapy for clear cell renal carcinoma","authors":"Aimin Jiang ,&nbsp;Wenqiang Liu ,&nbsp;Ying Liu ,&nbsp;Junyi Hu ,&nbsp;Baohua Zhu ,&nbsp;Yu Fang ,&nbsp;Xuenan Zhao ,&nbsp;Le Qu ,&nbsp;Juan Lu ,&nbsp;Bing Liu ,&nbsp;Lin Qi ,&nbsp;Chen Cai ,&nbsp;Peng Luo ,&nbsp;Linhui Wang","doi":"10.1016/j.jncc.2024.06.003","DOIUrl":"10.1016/j.jncc.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Emerging evidence suggests that cell deaths are involved in tumorigenesis and progression, which may be treated as a novel direction of cancers. Recently, a novel type of programmed cell death, disulfidptosis, was discovered. However, the detailed biological and clinical impact of disulfidptosis and related regulators remains largely unknown.</p></div><div><h3>Methods</h3><p>In this work, we first enrolled pancancer datasets and performed multi-omics analysis, including gene expression, DNA methylation, copy number variation and single nucleic variation profiles. Then we deciphered the biological implication of disulfidptosis in clear cell renal cell carcinoma (ccRCC) by machine learning. Finally, a novel agent targeting at disulfidptosis in ccRCC was identified and verified.</p></div><div><h3>Results</h3><p>We found that disulfidptosis regulators were dysregulated among cancers, which could be explained by aberrant DNA methylation and genomic mutation events. Disulfidptosis scores were depressed among cancers and negatively correlated with epithelial mesenchymal transition. Disulfidptosis regulators could satisfactorily stratify risk subgroups in ccRCC, and a novel subtype, DCS3, owning with disulfidptosis depression, insensitivity to immune therapy and aberrant genome instability were identified and verified. Moreover, treating DCS3 with NU1025 could significantly inhibit ccRCC malignancy.</p></div><div><h3>Conclusion</h3><p>This work provided a better understanding of disulfidptosis in cancers and new insights into individual management based on disulfidptosis.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 263-279"},"PeriodicalIF":7.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000462/pdfft?md5=b8b27d1b2e48460f1252ccf7d557b9d2&pid=1-s2.0-S2667005424000462-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary liver cancer organoids and their application to research and therapy","authors":"Xiaobin Zhu,&nbsp;Rajiv Trehan,&nbsp;Changqing Xie","doi":"10.1016/j.jncc.2024.06.002","DOIUrl":"10.1016/j.jncc.2024.06.002","url":null,"abstract":"<div><p>Primary liver cancer is a leading cause of death worldwide. To create advanced treatments for primary liver cancer, studies have utilized models such as 2D cell culture and <em>in vivo</em> animal models. Recent developments in cancer organoids have created the possibility for 3D <em>in vitro</em> cultures that recapitulates the cancer cell structure and operation as well as the tumor microenvironment (TME)<em>.</em> However, before organoids can be directly translated to clinical use, tissue processing and culture medium must be standardized with unified protocols to decrease variability in results. Herein, we present the wide variety of published methodologies used to derive liver cancer organoids from patient tumor tissues. Additionally, we summarize validation methodologies for organoids in terms of marker expression levels with immunohistochemistry as well as the presence of mutations and variants through RNA-sequencing. Primary liver cancer organoids have exciting applications allowing for faster drug testing at a larger scale. Primary liver cancer organoids also assisit in uncovering new mechanisms. Through the coculture of different immune cells and cancer organoids, organoids are now better able to recapitulate the liver cancer TME. In addition, it further aids in the investigation of drug development and drug resistance. Lastly, we posit that the usage of liver cancer organoids in animal models provides researchers a methodology to overcome the current limitations of culture systems.</p></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"4 3","pages":"Pages 195-202"},"PeriodicalIF":7.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667005424000450/pdfft?md5=71d57bff340d848aa3d9e6fef9dac00e&pid=1-s2.0-S2667005424000450-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}