{"title":"Current status and future prospects of cancer-derived immunoglobulins in pancreatic cancer.","authors":"Rui Ma, Fusheng Zhang, Yongsu Ma, Weikang Liu, Guangnian Liu, Yiran Chen, Jixin Zhang, Yinmo Yang, Xiaodong Tian","doi":"10.7150/jca.109497","DOIUrl":"10.7150/jca.109497","url":null,"abstract":"<p><p>Immunoglobulin (Ig) is an important part of the immune system, which is mainly produced by B cells to recognize and kill pathogens. In recent years, the concept of cancer-derived immunoglobulin (cIg) has been proposed. cIg is a special form of Ig found in tumor microenvironment, and the role of cIg in tumor development and potential clinical significance of cIg have attracted more attention recently. The discovery of cIg marks a new understanding of tumor immune response and provides new ideas for early diagnosis and individualized treatment of tumors. Pancreatic cancer is a highly malignant tumor that does not respond well to conventional treatment, and causes serious complications such as pancreatic cancer-associated diabetes. Therefore, exploring potential role of cIg in pancreatic cancer and the progression of pancreatic cancer-associated diabetes is expected to be a breakthrough to improve the diagnosis and treatment of pancreatic cancer and associated complications. This review aims to summarize current research status of cIg in the field of pancreatic cancer, and provide new ideas for modulating microenvironment of pancreatic cancer to improve diagnostic efficiency and therapeutic effect.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2673-2679"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.113348
Guixin Wang, Junming Cao, Yuxin Zhu, Shuo Wang, Yingxi Li, Yue Yu, Yao Tian, Xuchen Cao, Xin Wang
{"title":"Integrating Bulk RNA Sequencing and CRISPR-Cas9 Screening to Identify Proliferation-Related Genes for Prognostic Stratification in Breast Cancer.","authors":"Guixin Wang, Junming Cao, Yuxin Zhu, Shuo Wang, Yingxi Li, Yue Yu, Yao Tian, Xuchen Cao, Xin Wang","doi":"10.7150/jca.113348","DOIUrl":"https://doi.org/10.7150/jca.113348","url":null,"abstract":"<p><p>Breast cancer has become one of the most common malignant tumors in women. Although the emergence of molecular typing has greatly improved the prognosis of breast cancer patients, some patients still face drug resistance, recurrence and metastasis. At present, the development of effective biomarkers is still an important direction of breast cancer research. This study aims to provide new ideas for individualized treatment of breast cancer by identifying new biomarkers and constructing models to predict the prognosis of breast cancer patients. In this study, seven tumor-dependent genes associated with tumor proliferation were identified through the combined analysis of bulk-RNA sequencing and CRISPR-CAS9, and the mechanism of their potential promotion of tumor proliferation was initially analyzed. Immune infiltration analysis suggested these genes may be associated with the formation of immunosuppressive microenvironment. In addition, we constructed a gene signature based on seven genes that can predict prognostic risk in patients with breast cancer. The group with higher signature scores was associated with more GATA3 somatic mutations. Finally, we screened potential drugs suitable for high-risk groups to improve their outcomes. Our study provides potential therapeutic targets as well as individualized treatment strategies for breast cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2800-2811"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.110850
Ruiyi Deng, Mingrui Zou, Jianhui Qiu, Jiaheng Shang, Chaojian Yu, Peidong Tian, Yizhou Wang, Lin Cai, Jingcheng Zhou, Kan Gong
{"title":"Two-Sample Network Mendelian Randomization and Single-Cell Analysis Reveal the Causal Associations and Underlying Mechanisms Between Antihypertensive Drugs and Kidney Cancer.","authors":"Ruiyi Deng, Mingrui Zou, Jianhui Qiu, Jiaheng Shang, Chaojian Yu, Peidong Tian, Yizhou Wang, Lin Cai, Jingcheng Zhou, Kan Gong","doi":"10.7150/jca.110850","DOIUrl":"10.7150/jca.110850","url":null,"abstract":"<p><p><b>Background</b>: Antihypertensive drugs represent the most widely used drugs worldwide. However, the association between antihypertensive drugs and the risk of kidney cancer remains unclear. This study innovatively integrates multi-omics and causal inference approaches to investigate the long-term effects and potential mechanisms of 12 antihypertensive drug classes on kidney cancer risk. <b>Methods:</b> In this study, novel approaches including two-sample mendelian randomization (MR), summary-data-based mendelian randomization (SMR), two-step network MR, and single-cell transcriptomic analysis were employed. Single nucleotide polymorphisms (SNPs) were obtained from genome-wide association studies (GWASs) to proxy exposures and outcomes. The cis-expression quantitative trait loci (cis-eQTL) as the proxies of exposure were also obtained. MR estimates were generated using the inverse-variance weighted method or Wald ratio method. Sensitivity analyses were undertaken to interrogate the robustness of the main findings. Two-step network MR and single-cell analysis were specifically designed to dissect pathway-level mediation and expression patterns of identified targets. <b>Results</b>: In the main analysis, genetically proxied calcium-channel blockers (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.91-0.99, p=0.021) and vasodilator antihypertensives (OR: 0.86, 95% CI: 0.76-0.97, p=0.018) were suggestively associated with decreased risk of kidney cancer, whereas genetically proxied angiotensin-converting enzyme inhibitors (OR: 1.13, 95% CI: 1.00-1.27, p=0.043) was suggestively associated with increased risk of kidney cancer. Genetically proxied antiadrenergic agents (OR=0.94, 95% CI: 0.90-0.99, p=0.021) and centrally acting antihypertensives (OR=0.93, 95% CI: 0.88-0.98, p=0.010) were suggestively associated with a decreased risk of clear cell renal cell carcinoma. SMR analysis revealed that these suggestively significant associations might be driven by <i>CACNA1C</i>, <i>CALM1</i>, <i>ACE</i>, and <i>LTA4H</i>. Upon two-step network MR analyses, 10 pathways with directional consistency were identified, and the mediation proportion ranged from 3.22% to 7.12%. The influence of antihypertensive drugs on kidney cancer risk might be associated with their regulation of levels of blood cells and lipids. Single-cell analysis further revealed the expression patterns of the four identified targets in peripheral blood and tumor infiltrating immune cells. <b>Conclusion:</b> This study pioneers the integration of causal inference and single-cell omics to demonstrate that antihypertensive drugs modulate kidney cancer risk through target-specific mechanisms involving blood cell and lipid pathways. Our findings provide actionable targets (<i>CACNA1C</i>, <i>CALM1</i>, <i>ACE</i>, and <i>LTA4H</i>) for drug repurposing trials and underscore the clinical importance of personalized antihypertensive therapy in cancer prevention.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2690-2705"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy.","authors":"Dongzhang Li, Kaifeng Wang, Guantao Lou, Wangjian Li, Quan Ma, Yu'e Liu, Yongliang Chen","doi":"10.7150/jca.114137","DOIUrl":"10.7150/jca.114137","url":null,"abstract":"<p><p>Prostate cancer is an aggressive malignancy with high prevalence and significant mortality, characterized by its remarkable metabolic adaptability and immune complexity. Emerging evidence has highlighted the critical role of post-translational modifications (PTMs) in cancer biology, with protein lactylation gaining attention as a novel PTM with profound implications. Lactylation, derived from lactate, links the altered metabolic processes of tumor cells to diverse cellular functions, including epigenetic regulation and protein dynamics. It significantly influences tumor progression, immune evasion, and therapeutic resistance by modulating key immune cells within the tumor microenvironment. The immunosuppressive conditions created by lactate and lactylation favor tumor survival in prostate cancer. Thus, targeting lactylation offers innovative strategies for treating prostate cancer. By leveraging lactylation modulation, particularly in combination with immune checkpoint inhibitors, there is potential to enhance anti-tumor immune responses and improve treatment outcomes. This review explores the intersection of metabolic alterations and immune modulation, underscoring lactylation as a promising therapeutic avenue in prostate cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2706-2719"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.112394
Si-Yu Liu, Mu-Gen Dai, Wen-Feng Lu, Lei Liang, Jun-Wei Liu, Zhuo-Kai Li, Bin Ye
{"title":"Prognostic Value of Des-Gamma-Carboxy Prothrombin in AFP-Negative Hepatocellular Carcinoma Patients Following Liver Resection: <i>A Multicenter Study</i>.","authors":"Si-Yu Liu, Mu-Gen Dai, Wen-Feng Lu, Lei Liang, Jun-Wei Liu, Zhuo-Kai Li, Bin Ye","doi":"10.7150/jca.112394","DOIUrl":"10.7150/jca.112394","url":null,"abstract":"<p><p><b>Background:</b> Hepatocellular carcinoma (HCC) is a major global health concern with high postoperative recurrence rates. Des-gamma-carboxy prothrombin (DCP) is a promising biomarker for HCC prognosis, but its optimal cutoff value remains unclear, especially in AFP-negative patients. This study aimed to determine the ideal cutoff value of DCP in AFP-negative HCC patients following liver resection and to investigate its impact on long-term outcomes. <b>Methods:</b> This multicenter retrospective study included 661 patients who underwent curative HCC resection between 2015 and 2020 at three Chinese hospitals. Patients with AFP levels < 20 ng/mL were included. The primary endpoints were overall survival (OS) and time to recurrence (TTR). DCP levels were categorized as low (≤ 600 mAU/ml) and high (> 600 mAU/ml). <b>Results:</b> Among the 661 patients (median age 56 years; 88.4% men), 477 had low DCP levels and 184 had high DCP levels. Patients with high DCP levels had more aggressive tumor characteristics, including larger tumor size, microvascular invasion, and macrovascular invasion. The 5-year OS rates were 76.3% in the low DCP group vs. 57.6% in the high DCP group (<i>P</i> < 0.001), and the 5-year recurrence rates were 44.9% vs. 61.0% (<i>P</i> < 0.001), respectively. Multivariable analysis showed that high DCP levels were an independent risk factor for decreased OS (HR 1.548, 95%CI 1.135-2.111; <i>P</i> = 0.006) and increased TTR (HR 1.390, 95%CI 1.081-1.787; <i>P</i> = 0.010). <b>Conclusion:</b> A DCP cutoff value of 600 mAU/ml effectively stratifies AFP-negative HCC patients into high- and low-risk groups for survival and recurrence after liver resection. This cutoff value can guide clinical decision-making and improve prognostic accuracy.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2680-2689"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and Functional Characterization of CD-NTase Enzymes in Esophageal Squamous Cell Carcinoma.","authors":"Zhiwen Gong, Hongcheng Zhong, Shijiancong Liu, Xujie Xiao, Yuanquan Wu, Xiaojian Li, Qingdong Cao","doi":"10.7150/jca.100226","DOIUrl":"https://doi.org/10.7150/jca.100226","url":null,"abstract":"<p><p><b>Purpose:</b> The cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme family plays a critical role in tumor development, but its clinical significance and biological function in esophageal squamous cell carcinoma (ESCC) remain unclear. <b>Methods:</b> We analyzed 352 ESCC cases, including 260 from public datasets (TCGA, GSE53624, and GSE53622) and 92 from our clinical cohort. Candidate CD-NTase enzymes were validated through <i>in vivo</i> and <i>in vitro</i> experiments. <b>Results:</b> Analysis of 11 CD-NTase enzymes identified MB21D2 as the only significant prognostic factor in three clinical cohorts. Patients with low MB21D2 expression demonstrated markedly worse overall survival (OS). Multivariate analysis indicated that low MB21D2 was an independent prognostic factor (HR = 2.5, P =0.04; HR = 1.33, P =0.02; HR = 2.5, P =0.02). Furthermore, biological functional experiments showed that knockdown MB21D2 promotes proliferation, migration, and invasion in ESCC cells. While overexpression MB21D2 has the opposite effect. RNA-seq and western blotting analysis revealed that knockdown of MB21D2 activates markers associated with the Wnt/β-catenin signaling pathway, thereby promoting ESCC progression. <b>Conclusion:</b> MB21D2 serves as a critical prognostic and functional factor in ESCC progression, offering a potential therapeutic target for improving patient outcomes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2822-2836"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12244066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.112218
Wei Wu, Guoliang Li, Lixin Chai, Yating Yin, Xin Xu, Chenlun Han, Hongyong Liu, Yi Cao, Yumiao Wang, Qunhao Guo, Wenxuan Chen, Peter Wang, Zhijian Pan
{"title":"Revealing Potential Therapeutic Targets in Gastric Cancer through Inflammation and Protein-Protein Interaction Hub Networks.","authors":"Wei Wu, Guoliang Li, Lixin Chai, Yating Yin, Xin Xu, Chenlun Han, Hongyong Liu, Yi Cao, Yumiao Wang, Qunhao Guo, Wenxuan Chen, Peter Wang, Zhijian Pan","doi":"10.7150/jca.112218","DOIUrl":"10.7150/jca.112218","url":null,"abstract":"<p><p><b>Background:</b> Gastric cancer (GC) ranks second in incidence and mortality among digestive system cancer, following colorectal cancer. Currently treatment options are limited, and the prognosis for GC remains poor. <b>Methods:</b> Four bulk RNA sequencing (RNA-seq) datasets and two single-cell RNA sequencing (scRNA-seq) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Initially, we identified differentially expressed genes (DEGs). The intersection list of inflammatory response-related DEGs (IRR-DEGs) was utilized for enrichment analyses. Hub genes were extracted from the protein-protein interaction (PPI) network of DEGs, exploring their expression in the context of scRNA-seq landscapes and cell-cell communication. IRR hub DEGs were identified, and pathway and receptor-ligand pairs were analyzed at this gene level. <b>Results:</b> The analysis identified 69 DEGs in GC. Among these, 8 IRR-DEGs (SPP1, TIMP1, SERPINF1, TNFAIP6, LGALS1, LY6E, MSR1, and SELE) were closely associated with 19 types of immune cells and various lymphocytes. Of the 12 hub genes (SPP1, TIMP1, FSTL1, THY1, COL4A1, FBN1, ASPN, COL10A1, COL5A1, THBS2, LUM, and SPARC), their expression is significantly enhanced in stem cells, primarily involving communication with monocytes, and four prognostic-related genes were discovered. Two IRR hub DEGs indicated that the SPP1 signaling pathway, specifically the SPP1-CD44 ligand-receptor pairs, plays a critical role. <b>Conclusion:</b> We have collectively identified 18 genes that could serve as biomarkers for future GC targeting. The discovery of the SPP1-CD44 ligand-receptor axis not only elucidates a novel inflammatory signaling pathway driving tumor progression, but also provides a potential therapeutic target for disrupting cancer-stromal interactions. Importantly, these biomarkers lay the foundation for developing precision immunotherapies that target the inflammatory-immune axis in GC management.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2720-2736"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.112416
Cheng Wang, Ya Ding, Qikang Hu, Bin Wang, Shouzhi Xie, Zhi Yang, Zhe Zhang, Dexing Dai, An Xiong, Ruoman Sun, Yali Ling, Lei Qiu, Fenglei Yu, Zhongjian Xie, Muyun Peng
{"title":"Omega-6/Omega-3 Ratio as a Protective Factor in Lung Cancer: A Mendelian Randomization Study on Polyunsaturated Fatty Acids and Lung Adenocarcinoma Risk.","authors":"Cheng Wang, Ya Ding, Qikang Hu, Bin Wang, Shouzhi Xie, Zhi Yang, Zhe Zhang, Dexing Dai, An Xiong, Ruoman Sun, Yali Ling, Lei Qiu, Fenglei Yu, Zhongjian Xie, Muyun Peng","doi":"10.7150/jca.112416","DOIUrl":"10.7150/jca.112416","url":null,"abstract":"<p><p><b>Background:</b> While observational studies have reported conflicting associations between polyunsaturated fatty acids (PUFAs) and lung cancer risk, the causal role of specific PUFA subtypes remains unclear. <b>Methods:</b> Leveraging genome-wide association data from the UK Biobank and International Lung Cancer Consortium, we employed univariable, multivariable, and bidirectional Mendelian randomization (MR) analyses to investigate the causal effects of seven PUFA traits (including omega-3, DHA, EPA, omega-6, LA, AA, and the omega-6/omega-3 ratio) on lung cancer and its subtypes. <b>Results:</b> Our primary finding revealed a robust protective effect of a higher omega-6/omega-3 ratio against overall lung cancer (IVW: OR = 0.87; 95% CI: 0.78-0.96; <i>P_value</i> = 0.009) and lung adenocarcinoma (LUAD) (IVW: OR = 0.78; 95% CI: 0.67-0.89; <i>P_value</i> = 0.0005). Conversely, elevated omega-3 and DHA levels were associated with increased LUAD risk. These associations persisted after adjusting for BMI, smoking, and potential pleiotropy. <b>Conclusion:</b> This study provides the first causal evidence that a higher omega-6/omega-3 ratio reduces lung cancer risk, particularly LUAD, through multivariable and bidirectional Mendelian randomization analyses that account for BMI, smoking, and genetic pleiotropy. These findings highlight the ratio's potential as a novel and modifiable dietary target for prevention, offering actionable insights beyond prior studies focused on individual PUFA subtypes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2649-2662"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Journal of CancerPub Date : 2025-06-12eCollection Date: 2025-01-01DOI: 10.7150/jca.111026
Jialin Chen, Juan Chen, Yamei Ye, Linbin Lu, Xinying Guo, Simiao Gao, Lifang Liu, Hongyi Yang, Chun Lin, Xiong Chen
{"title":"Pretreatment Multi-sequence Contrast-Enhanced MRI to Predict Response to Immunotherapy in Unresectable Hepatocellular Carcinoma Using Transformer: A Multicenter Study.","authors":"Jialin Chen, Juan Chen, Yamei Ye, Linbin Lu, Xinying Guo, Simiao Gao, Lifang Liu, Hongyi Yang, Chun Lin, Xiong Chen","doi":"10.7150/jca.111026","DOIUrl":"10.7150/jca.111026","url":null,"abstract":"<p><p><b><i>Background:</i></b> Targeted combined immunotherapy (TCI) has shown certain antitumor effects in patients with unresectable hepatocellular carcinoma(uHCC), but only a subset of patients benefit. This study aims to develop a Transformer-based radiomics model to predict the objective response to combined therapy in patients with uHCC. <b><i>Methods:</i></b> This multicenter, retrospective study involved 264 HCC patients who underwent contrast-enhanced MRI prior to immunotherapy. The patients were divided into a training cohort(n=180) and a validation cohort(n=84). Using a multi-instance learning approach, tumor lesions in multi-sequence MRI were segmented into cross-sectional images, and features were extracted using the ResNet50 model. The Transformer model was then trained to predict the objective response rate (ORR). The prediction process was visualized using Grad-CAM and SHAP algorithms. Model performance was assessed using ROC and DCA curves, while survival analysis was conducted using Kaplan-Meier curves. <b><i>Results:</i></b> Among 264 patients, one achieved complete response (0.4%), 64 experienced partial response (24.2%). The ORR was 26.1% in the training group and 21.4% in the validation group. The model demonstrated high predictive accuracy, achieving a perfect area under the curve (AUC) of 1.000. Further validation using screenshot-based model inputs revealed an AUC of 0.929 (95% CI: 0.904, 0.947), confirming the model's clinical applicability. Kaplan-Meier analysis indicated that objective responders experienced better overall survival (OS) in both the training set (HR: 0.50, 95% CI: 0.27, 0.90) and the validation set (HR: 0.28, 95% CI: 0.08, 0.91). <b><i>Conclusion:</i></b> The deep learning framework combining ResNet50 and Transformer has proven its clinical applicability in predicting and assessing the efficacy of targeted combination immunotherapy in unresectable hepatocellular carcinoma, providing crucial guidance for clinical treatment decisions.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 8","pages":"2663-2672"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mismatch Repair Protein Deficiency and Its Relationship with Clinicopathological Factors in Endometrial Cancer: A Retrospective Study.","authors":"Okan Aytekin, Nesibe Cesur, Sercan Gozel, Sezin Eda Karsli, Abdurrahman Alp Tokalioglu, Fatih Kilic, Zeliha Firat Cuylan, Ilker Selcuk, Gunsu Kimyon Comert, Fazli Erdogan, Taner Turan","doi":"10.7150/jca.112935","DOIUrl":"https://doi.org/10.7150/jca.112935","url":null,"abstract":"<p><p><b>Background:</b> The present study aimed to determine the frequency of mismatch repair (MMR) protein expression loss, as identified using immunohistochemistry (IHC), in tumor cells of endometrial cancer patients and the potential associations between this loss of expression and various clinicopathological characteristics. <b>Methods:</b> The preparations were considered positive if tumor cells showed immunoreactivity that was equal to or stronger than that of positive controls and negative if tumor cells completely lost immunoreactivity. MMR proficiency was defined as positive IHC staining of all four proteins [MutL homolog 1 (MLH1), MutS homolog 2, MutS homolog 6 and PMS1 homolog 2 (PMS2)]. If at least one of them showed negative IHC staining, this was interpreted as mismatch repair protein deficiency (dMMR). <b>Results:</b> A total of 154 patients who met the criteria were included in this study. dMMR was observed in 54 (35.1%) patients in the study group. The MLH1 and PMS2 proteins were the most frequently lost, observed in 44 (28.8%) and 43 (27.9%) patients, respectively. Patients with dMMR were significantly older. However, there were no observed associations between dMMR and other clinicopathological factors. <b>Conclusions:</b> In conclusion, a notable association between the expression of MMR proteins and the age of the patient was observed in this cohort. No significant associations were detected between other clinical, surgical or pathological factors and MMR protein expression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"16 9","pages":"2778-2786"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12243964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}