Journal of Cancer最新文献

{"title":"Impact of Sarcopenia and Serum Creatinine on Clinical Outcomes after Tace in Hepatocellular Carcinoma.","authors":"Anna Rossetto, Valli De Re, Luca Montaldo, Vittorio Bresadola, Aron Zompicchiatti, Massimo Sponza, Daniele Piccolo, Giorgio Soardo, Serena Battista, Alessandro Mangogna, Alessandro Uzzau","doi":"10.7150/jca.127063","DOIUrl":"https://doi.org/10.7150/jca.127063","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE) is the standard treatment for intermediate unresectable hepatocellular carcinoma (HCC); however, reliable prognostic markers are still lacking. Sarcopenia has been proposed as a negative prognostic factor in HCC, but its impact on TACE outcomes remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed 48 HCC patients treated with TACE or transarterial embolization (TAE) at our institution (between 2013 and 2020). Sarcopenia was assessed on computed tomography (CT) or magnetic resonance imaging (MRI) scans at baseline, one month, and six months after treatment according to RECIST criteria.</p><p><strong>Results: </strong>At six months, 27 patients (61.4%) achieved complete or partial response, while 17 (38.6%) experienced stable or progressive disease; four patients were excluded due to missing follow-up data. Sarcopenia was more frequent among responders, increasing from 13.5% at baseline to 22.2% in 6 months, while it was initially absent in non-responders. Conversely, non-responders showed a later increase in sarcopenia (0% at baseline to 29.6% at 6 months), suggesting that late sarcopenia might reflect treatment-related metabolic changes. Overall, the prevalence of sarcopenia increased during follow-up. New-onset sarcopenia was more frequent in non-responders and was associated with lower serum creatinine levels , suggesting a possible link between treatment-related muscle loss and poor therapeutic response. Kaplan-Meier showed that smoking status was associated (p = 0.01) with poorer response at 6 months (), while sarcopenia and low creatinine levels showed borderline associations (p = 0.095).</p><p><strong>Conclusion: </strong>In this exploratory study, baseline CT-defined sarcopenia was not significantly associated with short-term response to TACE. However, treatment-related sarcopenia with low creatinine levels may reflect frailty during follow-up, and poorer therapeutic response. Given the small sample size and limited number of sarcopenic patients, these findings should be considered hypothesis-generating and require validation in larger prospective studies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"712-720"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772360","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":"High PMS2 Expression-Based Nomogram for Risk Stratification in Resected Hepatocellular Carcinoma: Application to Recurrence and Neoadjuvant Therapy Selection.","authors":"Wenchen Gong, Ruyu Han, Liyu Sun, Yingrui Gao, Zhiqiang Han, Yimeng Wang, Yuren Xia, Yukun Wei, Tianqiang Song, Lu Chen, Xiangdong Tian","doi":"10.7150/jca.131997","DOIUrl":"https://doi.org/10.7150/jca.131997","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) progresses rapidly with a poor prognosis due to the lack of reliable recurrence risk markers. Accurate prognostic stratification and individualized recurrence prediction remain major clinical challenges, hindering treatment optimization, particularly for adjuvant or neoadjuvant therapy. Although defects in mismatch repair (MMR) mechanisms are well studied, the role of elevated MMR protein expression-particularly post-meiotic segregation increased 2 (PMS2)-has remained unclear. This study aimed to investigate the prognostic value of PMS2 overexpression and develop an integrated predictive model to improve risk stratification and guide therapy selection. We analyzed 173 HCC patients and demonstrated that elevated PMS2 expression was significantly associated with poorer disease-free survival (DFS) (<i>p</i> < 0.001) and overall survival (OS) (<i>p</i> < 0.001). Cellular and animal models confirmed the pro-proliferative role of PMS2 in HCC progression. Multivariate analysis identified high PMS2 expression [HR: 3.109 (2.019-4.786), <i>p</i> < 0.001], high Phosphorylated-Protein Kinase B (p-AKT) expression [HR: 2.201 (1.304-3.715), <i>p</i> = 0.003], Barcelona Clinic Liver Cancer (BCLC) stage [HR: 2.635 (1.156-5.992), <i>p</i> = 0.021], and poor pathological differentiation [HR: 1.729 (1.098-2.722), <i>p</i> = 0.018] as independent risk factors for poor DFS. The nomogram based on these factors demonstrated good predictive performance and effectively stratified patients into high-risk and low-risk groups (<i>p</i> < 0.001). In an exploratory analysis of a separate cohort receiving neoadjuvant immunotherapy, preliminary data suggested that high-risk patients might derive greater survival benefit (p=0.044). These findings highlight PMS2 overexpression as a potential prognostic biomarker and provide a promising predictive tool for personalized treatment planning in HCC, warranting further validation in prospective studies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"771-786"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772413","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":"Prior Cancer among Men Diagnosed with Breast Cancer is Associated with Worse Overall Survival but Equivalent Breast Cancer-Specific Survival.","authors":"Aniruddha Rathod, Caitlin C Murphy, Kathryn L Shahan, Sandi L Pruitt","doi":"10.7150/jca.119554","DOIUrl":"https://doi.org/10.7150/jca.119554","url":null,"abstract":"<p><strong>Background: </strong>Men newly diagnosed with breast cancer (BC) who have survived prior cancer are often excluded from clinical trials, despite limited evidence on how prior cancer impacts BC outcomes. Understanding survival of those with prior cancer is crucial for trial sponsors and investigators to make informed eligibility decisions. Using Surveillance, Epidemiology, and End Results (SEER) data, we investigated the impact of prior cancer on survival in men diagnosed with BC between 2011 and 2015.</p><p><strong>Methods: </strong>We evaluated the prevalence of prior cancer of a different type in adult men with BC and analyzed its effects on overall and BC-specific survival using Cox models and the Fine and Gray method to account for competing risks of death. Models adjusted for covariates including patient, tumor, and treatment factors.</p><p><strong>Results: </strong>Among 1,923 men with BC, 241 (12.5%) had a prior cancer of different type. There were 904 deaths from any cause including 365 from BC. Median overall survival was 10.1 years. Adjusted models demonstrated worse overall survival for men with prior cancer (HR=1.3, 95% CI: 1.1, 1.6) but no statistically significant difference in BC-specific survival (sdHR=0.9, 95% CI: 0.7, 1.4) between the groups.</p><p><strong>Conclusions: </strong>Despite worse overall survival, men with prior cancer did not have worse BC-specific survival, suggesting their inclusion in trials is unlikely to introduce bias in BC-specific survival.</p><p><strong>Implications for cancer survivors: </strong>Including men with prior cancer in trials may enhance trial accrual, inclusivity, and generalizability, critical aspects of research studies for this rare cancer in which accrual is already a challenge.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"721-729"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772387","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":"Inflammation Drives Phosphorylation and Acetylation of MutS Homolog 3 and Interaction with Cytosolic HDAC6.","authors":"Stephanie S Tseng-Rogenski, Minoru Koi, John M Carethers","doi":"10.7150/jca.131728","DOIUrl":"https://doi.org/10.7150/jca.131728","url":null,"abstract":"<p><strong>Background: </strong>MutS Homolog 3 (MSH3), part of the MutSβ DNA mismatch repair complex with MSH2, can reversibly translocate from the nucleus to cytosol via IL-6 signaling, abrogating nuclear MutSβ function and is associated with metastasis and poor patient survival. A polymorphism consisting of deletion of 27-bp proximate to the nuclear localization signal (NLS) (Δ27bpMSH3) allows MSH3 cytosolic retention with IL-6 or oxidative stress. Here, we examined for IL-6-induced post-translational modifications associated with MSH3 cytosolic translocation.</p><p><strong>Methods: </strong>We utilized MSH3-genotyped colon cancer cell lines after IL-6 treatment to assess post-translational modification of MSH3 via Western blots (WB). We modified sequences within the MSH3-NLS-EGFP reporter construct to assess MSH3 localization via immunofluorescent microscopy and WB after nuclear-cytosolic fractionation. Immunoprecipitation (IP) followed by WB was used to study post-IL-6-induced interactions with MSH3.</p><p><strong>Results: </strong>MSH3 and Δ27bpMSH3 increased serine phosphorylation after 2 hours followed by tyrosine phosphorylation 18 hours post IL-6 treatment, with Δ27bpMSH3 showing more robust phosphorylation than MSH3 likely due to increased cytosolic translocation. MSH3 cytosolic localization was enhanced by acetylation of lysine residues within MSH3's NLS, specifically at residues K⁹⁹, K¹⁰⁰ and K¹⁰³. With the observed acetylation control for MSH3 cytosolic localization, IP experiments demonstrate binding of cytosolic-located histone deacetylase 6 (HDAC6) to acetylated Δ27bpMSH3.</p><p><strong>Conclusions: </strong>Polymorphic MSH3 undergoes serine/tyrosine phosphorylation and NLS acetylation upon IL-6 signaling for its nuclear-cytosolic shift and binds HDAC6 in the cytosol which may contribute to anticipated deacetylation and MSH3 protein stability when separated from MSH2. These modifications might be targeted to regulate MSH3's intracellular localization.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"730-739"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772384","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":"Roles of Cellular Neighborhoods in Lung Cancer.","authors":"Rui Bai, Wenjie Sun","doi":"10.7150/jca.132848","DOIUrl":"https://doi.org/10.7150/jca.132848","url":null,"abstract":"<p><p>The occurrence and development of lung cancer (LC) involve complex interactions between various cell types in the tumor microenvironment (TME). Understanding the spatial distribution and interaction mechanisms of these cells may be the key to overcoming LC. The advancements of single-cell and spatial transcriptome techniques have promoted our understanding of cellular neighborhoods (CNs) and their functions in the pathogenesis of LC. In this review, we focus on the impact of different etiologies on LC CNs and the current research status of CNs in LC. This review may provide new insights into the molecular mechanisms of LC pathogenesis, develop more refined classification principles for LC diagnosis, and offer new perspectives for LC treatment.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"759-770"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772411","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":"An integrated bulk and single-cell transcriptomic analysis reveals stemness-driven immune regulation and therapeutic vulnerability in colorectal cancer.","authors":"I-Hung Chen, Kai-Fu Chang, Chien-Cheng Chao, Chung-Hsien Lin, Chih-Hsuan Chang, Ching-Chung Ko, Hui-Ru Lin, Chi-Jen Wu, Chien-Han Yuan, Sachin Kumar, Dahlak Daniel Solomon, Do Thi Minh Xuan, Neethu Palekkode, Ayman Fathima, Yung-Kuo Lee, Chung-Bao Hsieh, Yuen-Jung Wu","doi":"10.7150/jca.132694","DOIUrl":"https://doi.org/10.7150/jca.132694","url":null,"abstract":"<p><p>Tumor stemness is increasingly recognized as a key contributor to tumor heterogeneity, immune regulation, and therapeutic resistance in colorectal cancer (CRC). In this study, we developed a stemness-based risk model using bulk transcriptomic data from The Cancer Genome Atlas and evaluated its prognostic and therapeutic relevance through integrative analyses. The proposed risk score robustly stratified patients into distinct prognostic groups and remained an independent predictor of overall survival after adjustment for clinicopathological variables. Stemness-high tumors exhibited altered immune infiltration patterns and coordinated upregulation of immune checkpoint-related genes. Although the association between stemness score and immune evasion potential was modest, its clinical relevance was supported by validation in independent immunotherapy-treated cohorts, where low-risk patients demonstrated improved survival and higher response rates. Single-cell RNA sequencing (scRNA-seq) analysis further revealed that enhanced stemness and dedifferentiation were predominantly localized within malignant epithelial cells. Together, these findings establish tumor stemness as a central determinant of prognosis, immune regulation, and therapeutic vulnerability in CRC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"740-758"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772400","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":"WISP-3 promotes angiogenesis in non-small cell lung cancer through p38/JNK-c-Jun-mediated PDGF-A upregulation.","authors":"En-Ming Chang, Syuan-Ling Lin, Ching-Yuan Cheng, Chih-Hsin Tang, Yu-Chen Chen, Chiang-Wen Lee, Chih-Yang Lin","doi":"10.7150/jca.127681","DOIUrl":"https://doi.org/10.7150/jca.127681","url":null,"abstract":"<p><p>Angiogenesis is a pivotal process for tumor progression and metastasis in non-small cell lung cancer (NSCLC). However, the molecular mechanisms by which WNT1-inducible signaling pathway protein 3 (WISP-3) contributes to NSCLC angiogenesis remain poorly defined. This study investigated the role of WISP-3 in regulating pro-angiogenic signaling in lung adenocarcinoma (LUAD) cells. Conditioned medium from H1299 and A549 cells treated with recombinant WISP-3 (0-100 ng/mL) significantly and dose-dependently enhanced the tube formation of human umbilical vein endothelial cells (HUVECs). WISP-3 selectively upregulated platelet-derived growth factor A (PDGF-A) expression at both mRNA and protein levels in NSCLC cell lines, while other angiogenic factors remained unaffected. Notably, knockdown of PDGF-A using siRNA markedly abolished WISP-3-induced HUVEC tube formation, confirming PDGF-A as a critical mediator in this process. Mechanistically, WISP-3 rapidly triggered the phosphorylation of p38 and JNK signaling pathways. These activations led to the phosphorylation of the transcription factor c-Jun, which in turn promoted PDGF-A gene expression. Pharmacological inhibition of p38 (Adezmapimod), JNK (SP600125), or c-Jun (T-5224) effectively suppressed WISP-3-induced c-Jun activation, PDGF-A expression, and subsequent angiogenesis. Collectively, our findings identify a novel WISP-3/p38-JNK/c-Jun/PDGF-A signaling axis that drives vascular remodeling in NSCLC. Targeting WISP-3 or its downstream effectors may represent a promising therapeutic strategy for anti-angiogenic treatment in lung cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 4","pages":"787-796"},"PeriodicalIF":3.2,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772376","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":"Integrative Multi-Omics and Single-Cell Profiling Identify Chitinase Domain Containing Protein 1 (CHID1) as a Prognostic Biomarker in Glioblastoma.","authors":"Sachin Kumar, Chung-Che Wu, Dahlak Daniel Solomon, Juan Lorell Ngadio, Do Thi Minh Xuan, Ching-Chung Ko, Neethu Palekkode, Ayman Fathima, Hung-Yun Lin, Hui-Ru Lin, Chih-Yang Wang, Yung-Kuo Lee, Ngoc Uyen Nhi Nguyen","doi":"10.7150/jca.130519","DOIUrl":"10.7150/jca.130519","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by high recurrence, metabolic plasticity, and complex tumor microenvironmental interactions. The human chitinase and chitinase-like protein family includes five members (CHI3L1, CHI3L2, CHIA, CHID1, and CHIT1) that share conserved chitinase-related domains but exhibit diverse biological functions in immune regulation and tissue remodeling. While chitinase-like proteins are recognized as mesenchymal-associated markers, however, the role of CHID1 in GBM remains largely unexplored. An integrative multi-omics strategy combining TCGA-GBM and CGGA transcriptomic datasets, single-cell RNA sequencing, and enrichment analyses (GSEA, GO, KEGG, and MetaCore) were used to investigate CHID1 expression patterns and associated transcriptional programs. Pharmacogenomic correlations and molecular docking were used to explore potential drug-response associations. CHID1 showed higher expression in GBM compared to the normal brain and was associated with poor overall survival. A single-cell analysis showed tumor-associated expression patterns of CHID1 across malignant samples. Pathway enrichment analyses identified transcriptional programs related to oxidative phosphorylation, redox-related processes, DNA repair, and cell cycle pathways. Collectively, this study provides a comprehensive multi-cohort and multi-modal characterization of CHID1 expression in GBM, integrating bulk transcriptomics, single-cell RNA sequencing, and tissue-level validation. The findings establish CHID1 as a GBM-associated transcriptional marker linked to metabolic and redox-related programs and provide a systematic resource for future investigations into chitinase family-related biology in GBM.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 3","pages":"662-678"},"PeriodicalIF":3.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498999","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":"Recurrence of Adult Granulosa Cell Tumors: The Factors Affecting Secondary Recurrence and Survival After Recurrence.","authors":"Hasan Volkan Ege, Derman Başaran, Murat Gültekin, Nejat Özgül, Nurattin Boran, Sevgi Koç, Yaprak Üstün, Caner Çakır, Dilek Yüksel, Okan Oktar, Gökçen Ege, Abdurrahman Alp Tokalıoğlu, Mustafa Şahin, Yeşim Uçar, Fatih Kılıç, Okan Aytekin, Burak Ersak, Mehmet Ünsal, Özlem Moraloğlu Tekin, Çiğdem Kılıç, Özgür Koçak, Çağatayhan Öztürk, Salih Taşkın, Fırat Ortaç, Işın Üreyen, Tayfun Toptaş, Sevda Baş, Mehmet Ali Narin, Tolga Taşçı, Gökhan Uçar, Mehmet Ali Şendur, Burak Civelek, Doğan Uncu, Özgür Erdoğan, Muzaffer Sancı, Hakan Raşit Yalçın, İlker Selçuk, Taner Turan","doi":"10.7150/jca.127596","DOIUrl":"10.7150/jca.127596","url":null,"abstract":"<p><strong>Introduction: </strong>Adult-type granulosa cell tumors (AGCTs) are rare ovarian neoplasms with a low overall incidence of recurrence, and also data on secondary recurrence and survival after relapse remain limited. This study aimed to identify factors associated with secondary recurrence and survival after recurrence in patients with recurrent AGCTs.</p><p><strong>Methods: </strong>This multicenter retrospective study included 52 patients with recurrent AGCTs identified among 484 patients treated between 2000 and 2023. Clinical characteristics, treatment modalities, and outcomes were analyzed, with a particular focus on factors associated with secondary recurrence and survival after first recurrence. Recurrence-free survival and overall survival after first recurrence (OS-FR) were evaluated using Kaplan-Meier analysis.</p><p><strong>Results: </strong>The mean follow-up duration was 99.2 ± 61.5 months. Secondary recurrence occurred in 17 patients (32.7%). A serum CA-125 level >35 U/mL at the time of first recurrence was significantly associated with an increased risk of secondary recurrence (p=0.01). Factors significantly associated with improved OS-FR included a CA-125 level ≤35 U/mL at initial diagnosis and at first recurrence, absence of residual disease following surgery for the first recurrence, and administration of salvage chemotherapy (all p<0.05). In subgroup analysis, salvage chemotherapy was associated with improved OS-FR in patients with residual disease or those who did not undergo surgery (p < 0.01), but not in patients who achieved complete cytoreduction (p = 0.67).</p><p><strong>Conclusions: </strong>Secondary recurrence remains a significant clinical challenge in AGCTs. Serum CA-125 levels, surgical outcomes at first recurrence, and the use of salvage chemotherapy may help management strategies in recurrent disease.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 3","pages":"637-645"},"PeriodicalIF":3.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499014","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":"Integrative analysis of lysosome-dependent cell death related molecular subtypes and prognosis prediction in papillary thyroid carcinoma.","authors":"Ying Xu, Qiong Wang, Na Zhang, Fugeng He, Xiaochun Mao","doi":"10.7150/jca.129191","DOIUrl":"10.7150/jca.129191","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, shows marked clinical heterogeneity despite generally favorable outcomes. Lysosome-dependent cell death (LDCD), a form of programmed death triggered by lysosomal membrane permeabilization, has emerged as a potential cancer therapy target, but its role in PTC remains unclear.</p><p><strong>Methods: </strong>Transcriptomic data from public cohorts were analyzed to identify LDCD-related genes (LDCDRG) associated with PTC prognosis. Cox analysis and LASSO regression analyses were performed to construct a prognostic model. Immune landscape, drug sensitivity, and single-cell expression profiles were examined. Functional experiments were conducted <i>in vitro</i> to verify the biological effects of the key gene <i>LMTK3</i> on PTC cell proliferation, viability, and invasion.</p><p><strong>Results: </strong>Nineteen LDCDRG were differentially expressed between normal and tumor tissues, defining three molecular subtypes with distinct immune and prognostic profiles. A six-LDCDRG signature (<i>LMTK3</i>, <i>MCM5</i>, <i>NXF1</i>, <i>TUBB4B</i>, <i>LIMCH1</i> and <i>APH1B</i>) effectively stratified patients into high- and low-risk groups with significantly different survival outcomes and acceptable predictive performance. High-risk patients showed reduced immune infiltration and lower predicted immunotherapy-related immune activity. LMTK3, the highest-risk gene, was highly expressed in PTC cells, and its knockdown suppressed proliferation and invasion <i>in vitro.</i></p><p><strong>Conclusions: </strong>The established six-LDCDRG signature provides an exploratory tool for risk stratification and survival prediction, while <i>LMTK3</i> emerges as potential target worthy of further investigation. These findings deepen our understanding of lysosome-dependent cell death in thyroid carcinogenesis and may provide insights into the development of personalized management strategies and novel treatment approaches for high-risk PTC patients.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 3","pages":"646-661"},"PeriodicalIF":3.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499048","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}