{"title":"Evaluating the prognostic value of estrogen receptor status in stage III MMR-proficient endometrial cancer: real-world data from an Asian population.","authors":"Szu-Wei Huang, Hao Lin, Chao-Cheng Huang, Yu-Che Ou, Hung-Chun Fu, Ching-Chou Tsai, Ying-Wen Wang, Ying-Yi Chen, Fu-Chen Kuo, Chen-Hsuan Wu","doi":"10.62347/WLKJ7269","DOIUrl":"10.62347/WLKJ7269","url":null,"abstract":"<p><p>To evaluate the prognostic value of estrogen receptor (ER) expression in mismatch repair-proficient (MMRp) stage III endometrial cancer (EC) in an Asian cohort using an immunohistochemistry (IHC) - based molecular classification, we retrospectively analyzed patients with stage III EC classified by IHC into three molecular subtypes: mismatch repair-deficient (MMRd), TP53-mutant, and MMRp. The MMRp group was further stratified by ER expression (10% cutoff) into ER-positive and ER-negative subgroups, yielding four molecular subtypes. Clinicopathological features and survival outcomes were compared. Ninety-five patients were included: 7 (7.4%) with MMRp ER-negative, 34 (35.8%) with MMRp ER-positive, 27 (28.4%) with MMRd, and 27 (28.4%) with TP53-mutant tumors. With a median follow-up of 61 months, progression-free survival (PFS) and cancer-specific survival (CSS) differed significantly across four IHC-based subtypes (log-rank P = 0.0013 and P<0.0001, respectively). In multivariate Firth's penalized Cox regression, MMRp ER-negative status was an independent predictor of poor PFS (HR 4.91; 95% CI, 1.43-15.80) and CSS (HR 7.44; 95% CI, 1.85-30.80), independent of histologic grade. Even within low-risk MMRp endometrioid grade 1-2 tumors, ER-negativity identified a high-risk subset (12.1%, 4/33). To our knowledge, this is among the first studies to evaluate the prognostic relevance of ER expression in stage III MMRp EC in an Asian cohort using a pragmatic IHC-based approach. Low ER expression identified a distinct high-risk subgroup whose outcomes approached those of TP53-mutant tumors.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3504-3515"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928635","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":"Fear of disease recurrence in postoperative craniopharyngioma patients: status, influencing factors, and associations with social support and coping strategies.","authors":"Yangbo Li, Yali Zhan, Xiaoqiang Lin, Chengpeng Zhan, Jiamin Liu, Wei Liu","doi":"10.62347/NGDS1408","DOIUrl":"10.62347/NGDS1408","url":null,"abstract":"<p><p>This prospective observational study aimed to investigate the status of social support and fear of cancer recurrence (FCR), as well as the influencing factors, in patients after craniopharyngioma surgery. A total of 168 postoperative craniopharyngioma patients were enrolled using questionnaire survey, including general data questionnaire, Social Support Rating Scale (SSRS), Fear of Progression Questionnaire Short Form (FoP-Q-SF), and Medical Coping Modes Questionnaire (MCMQ). The mean FCR score was 39.54±8.65, and 71.43% (120/168) of patients had clinically significant FCR (score ≥34). Univariate analysis showed that FCR was associated with education level, employment status, family history of tumors, symptom distress, personality traits, and chronic comorbidities (P<0.05). Multiple linear regression indicated that education level (β = -1.126, P<0.001), symptom distress (β = -2.661, P = 0.021), personality orientation (β = 3.153, P<0.001), and resignation coping strategy (β = 1.042, P<0.001) were independent predictors of FCR. FCR is prevalent in patients with postoperative craniopharyngioma and is independently affected by education level, symptom distress, personality traits, and negative coping strategies. Targeted psychological interventions should be provided to improve mental health and prognosis.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3526-3541"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928644","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}
Zhenni Sun, Yasai Yao, Zhijian Xu, Qingnuan Kong, Mi Zhou, Tao Qin, Yafei Han, Ruyong Yao, Lu Yue
{"title":"LncRNA DNAJC3-AS1 promotes gastric cancer malignancy through miR-576-5p-mediated upregulation of LYPLA1.","authors":"Zhenni Sun, Yasai Yao, Zhijian Xu, Qingnuan Kong, Mi Zhou, Tao Qin, Yafei Han, Ruyong Yao, Lu Yue","doi":"10.62347/MGRO5103","DOIUrl":"10.62347/MGRO5103","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are involved in tumor progression, but the role of lnc-DNAJC3-AS1 in gastric cancer (GC) remains unclear. This study aimed to investigate the biological function and regulatory mechanism of lnc-DNAJC3-AS1 in GC. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression levels of lnc-DNAJC3-AS1, miR-576-5p, and LYPLA1, and Western blot was used to analyze protein expression. The Cancer Genome Atlas (TCGA) database and clinical samples were used to evaluate their clinical relevance. Cell viability, cell cycle distribution, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing, Transwell, and immunofluorescence assays. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and rescue assays were performed to explore the potential regulatory relationship among lnc-DNAJC3-AS1, miR-576-5p, and LYPLA1. A xenograft tumor model was also established to evaluate the role of lnc-DNAJC3-AS1 in vivo. The results showed that lnc-DNAJC3-AS1 and LYPLA1 were upregulated, whereas miR-576-5p was downregulated in GC tissues and cells. Knockdown of lnc-DNAJC3-AS1 inhibited GC cell viability, migration, and invasion, induced G0/G1 phase arrest and apoptosis, and suppressed tumor growth in vivo. Mechanistically, lnc-DNAJC3-AS1 was mainly localized in the cytoplasm and was associated with miR-576-5p-related RNA-induced silencing complex (RISC) complexes. MiR-576-5p targeted LYPLA1, and restoration of miR-576-5p or knockdown of LYPLA1 partially attenuated the effects of lnc-DNAJC3-AS1 overexpression on GC cell phenotypes and LYPLA1 enzymatic activity. These findings suggest that lnc-DNAJC3-AS1 promotes GC progression, at least in part, through the miR-576-5p/LYPLA1 pathway, providing a potential target for GC treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3556-3573"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928665","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}
Fubo Li, Yan Guo, Zhuangyu Xu, Wenxin Li, Yi Dong, Fan Xu
{"title":"Treating T24 cells with erianin restores gefitinib drug sensitivity by regulating MYLK to inhibit EGFR and EMT processes.","authors":"Fubo Li, Yan Guo, Zhuangyu Xu, Wenxin Li, Yi Dong, Fan Xu","doi":"10.62347/YZXW4438","DOIUrl":"10.62347/YZXW4438","url":null,"abstract":"<p><p>Erianin exerts anticancer effects in bladder cancer, although its underlying molecular mechanisms remain unclear. This study used online databases to identify erianin-related drug targets and bladder cancer-associated disease targets and to predict the potential signaling pathways involved. Intersecting genes were enriched in the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance signaling pathway, and high myosin light chain kinase (MYLK) expression was associated with poor prognosis. A gefitinib-resistant bladder cancer cell line was established to evaluate the role of MYLK. Erianin inhibited MYLK and EGFR protein expression, blocked EGFR signaling and epithelial-mesenchymal transition (EMT), restored gefitinib sensitivity, and suppressed the proliferation, invasion, and migration of bladder cancer cells.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3377-3393"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928680","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":"IL-23 promotes PD-L1 expression and tumor immune evasion via METTL16 pathway.","authors":"Xueshan Pan, Yue Wang, Jingjing Luo, Xingna Dai, Jialin Zhang, Rui Zheng, Hui Xu, Yingjie Zhang, Jifeng Zhang, Zhiwei Wang, Tong Cao, Jia Ma","doi":"10.62347/DDRA7133","DOIUrl":"10.62347/DDRA7133","url":null,"abstract":"<p><p>Interleukin-23 (IL-23) is a pivotal cytokine implicated in tumor progression and immune evasion, yet its precise molecular mechanisms remain incompletely characterized. In this study, we elucidate that IL-23 upregulates METTL16, which in turn enhances PD-L1 expression and facilitates tumor immune escape. Integrated analysis of TCGA and GEO datasets revealed the co-upregulation of IL-23 and METTL16 in lung and colon carcinomas, both of which are correlated with poor clinical outcomes. Mechanistically, IL-23 induces METTL16 expression in cancer cells via JAK-STAT3 pathway-mediated transcriptional activation. Notably, METTL16 augments PD-L1 levels via an m6A-independent mechanism by directly binding to PD-L1 and impeding its SPOP-mediated ubiquitination and proteasomal degradation. In vivo, METTL16 promotes colon cancer xenograft growth while concurrently suppressing CD8<sup>+</sup> T cell infiltration and IFN-γ secretion within the tumor microenvironment. Collectively, these findings establish the IL-23/METTL16/PD-L1 axis as a novel regulatory pathway and potential therapeutic target in cancer immunotherapy.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3678-3693"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928679","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":"A seven-variable clinical prediction model for bone metastasis at initial diagnosis of prostate cancer.","authors":"Yongkang Ni, Ning Tao, Hengqing An","doi":"10.62347/CIEN9343","DOIUrl":"10.62347/CIEN9343","url":null,"abstract":"<p><p>Decisions about bone-imaging workup at initial diagnosis of prostate cancer often have to be made before PSMA-PET/CT or other specialized investigations are available, particularly in resource-constrained settings. Many recent prediction models rely on advanced imaging, radiomics, specialized biomarkers, or large registry infrastructures and may therefore be difficult to apply in this earlier decision context. We retrospectively reviewed records of 291 consecutive men with newly diagnosed, histopathologically confirmed prostate adenocarcinoma admitted to the First Affiliated Hospital of Xinjiang Medical University between March 2011 and November 2023. Starting from 93 candidate predictors, we applied a five-stage hybrid selection procedure (univariable screening, exploratory LASSO, clinical prescreening, data-quality review, and confirmatory LASSO) to derive the final variable set. The retained predictors were entered into a multivariable logistic regression and visualized as a nomogram. Model behavior was characterized through discrimination, calibration, decision curve analysis, and 1,000-iteration bootstrap optimism correction. Of the 291 patients, 113 (38.8%) had bone metastasis. The final 7-variable model included anemia status, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, age, Gleason score (three groups), and total prostate-specific antigen (tPSA). The apparent AUC was 0.736 (95% CI 0.674-0.799); the bootstrap bias-corrected AUC was 0.713 with a calibration slope of 0.933. This seven-variable model uses routinely available variables and showed moderate discrimination with stable calibration; external validation in independent samples is required before clinical use.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3488-3503"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928707","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":"Immunoscore based on CD3<sup>+</sup> and cytotoxic CD8<sup>+</sup> T-lymphocyte densities predicts prognosis and chemotherapy efficacy in esophageal squamous cell carcinoma.","authors":"Nai-Jun Fan, Fu-Lin Li, Nian-Long Meng, Xue-Xia Lv, Tian Yun, Yan-Sha Cao, Cheng Wang, Xu-Tao Yuan, Ya-Xi Wang, Qing-Yin Liu, Chang-Song Wang","doi":"10.62347/BYFJ4889","DOIUrl":"10.62347/BYFJ4889","url":null,"abstract":"<p><p>The current American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (AJCC/UICC-TNM) staging system for esophageal squamous cell carcinoma (ESCC) does not incorporate an immune-based classification. This study aimed to evaluate the prognostic value of the Immunoscore (IS), based on the densities of CD3<sup>+</sup> and cytotoxic CD8<sup>+</sup> T lymphocytes, and its ability to predict the efficacy of chemotherapy in patients with ESCC. The IS was determined by immunohistochemical staining for CD3 and CD8 and was calculated according to the densities of CD3<sup>+</sup> and CD8<sup>+</sup> cells in the tumor center (CT) and invasive margin (IM). A total of 255 patients with previously untreated ESCC who underwent curative resection were randomly assigned to training and validation sets. Among them, 169 received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were the endpoints of the prognostic analyses. In the training set, patients with a high IS had the lowest risk of recurrence. The 5-year RFS rates were 9.7%, 44.7%, and 90.1% among patients with low, intermediate, and high IS values, respectively (hazard ratio [HR] for high vs. low IS, 0.29; P<0.001). A high IS was also significantly associated with prolonged OS (P<0.001). Multivariable Cox regression analysis showed that the associations of IS with RFS and OS were independent of clinicopathological variables (HR for high vs. low IS: 0.29 for RFS and 0.53 for OS; both P<0.001). The IS accounted for the largest proportion of the total χ<sup>2</sup> statistic in predicting both RFS and OS (P<0.001). The IS was also significantly associated with RFS and OS among patients who received postoperative chemotherapy (both P<0.001). These findings were further confirmed in the validation set. The IS provides more accurate prognostic stratification and prediction of chemotherapy efficacy. It may complement the AJCC/UICC-TNM staging system in patients with operable ESCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3445-3460"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928692","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}
Dejun Fan, Jun Li, Ruirui Niu, Feiyue Zhou, Jun Hu, Li Yang
{"title":"Clinical and MRI features for predicting maximum cancer involvement of >50% in a single biopsy core among patients diagnosed with prostate cancer at initial systematic biopsy: a machine learning study.","authors":"Dejun Fan, Jun Li, Ruirui Niu, Feiyue Zhou, Jun Hu, Li Yang","doi":"10.62347/ROGZ7613","DOIUrl":"10.62347/ROGZ7613","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the conditional predictive value of prebiopsy clinical variables and magnetic resonance imaging (MRI) features for maximum cancer involvement of >50% in a single biopsy core among patients diagnosed with prostate cancer at initial systematic biopsy and to compare the internally validated performance of different machine learning models.</p><p><strong>Methods: </strong>This retrospective study included patients diagnosed with prostate cancer at initial systematic biopsy at the First Affiliated Hospital of Dali University between April 2023 and February 2026. Clinical, imaging, and combined models were developed to predict maximum cancer involvement of >50% in a single biopsy core using age, body mass index, total prostate-specific antigen (tPSA), prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, and MRI features related to tumor extent. Logistic regression, elastic net, random forest, and extreme gradient boosting (XGBoost) were compared using the combined predictors. Discrimination, calibration, and overall prediction error were evaluated using five repeats of stratified five-fold cross-validation and bootstrap resampling.</p><p><strong>Results: </strong>Among 127 patients, 85 (66.9%) had maximum cancer involvement of >50% in a single biopsy core. The areas under the receiver operating characteristic curve (AUROCs) of the clinical, imaging, and combined models were 0.822, 0.773, and 0.823, respectively. The combined model showed no clear incremental discrimination over the clinical model but had a lower overall prediction error than the imaging model. Among the four algorithms using the combined predictors, elastic net achieved the highest AUROC (0.823), whereas XGBoost achieved the highest average precision (0.878), the lowest Brier score (0.151), and favorable calibration. tPSA and PI-RADS score showed relatively consistent predictive contributions across models. Sensitivity analyses yielded generally similar AUROCs, although Brier scores and calibration slopes varied.</p><p><strong>Conclusion: </strong>Prebiopsy clinical variables and MRI features enabled risk stratification for maximum cancer involvement of >50% in a single biopsy core among patients diagnosed with prostate cancer at initial systematic biopsy. Elastic net and XGBoost demonstrated favorable overall predictive performance, while tPSA and PI-RADS score showed relatively consistent contributions. External validation in independent cohorts is required.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3461-3475"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928880","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-fat diet-responsive DNM1 promotes hepatocellular carcinoma progression and predicts poor prognosis in viral-associated patients.","authors":"Po-Ming Chen, Huai-Yi Huang, Hsin-Hung Chen, Rong-Fu Chen, En-Pei Isabel Chiang","doi":"10.62347/KHKV1727","DOIUrl":"10.62347/KHKV1727","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) arises from diverse etiologies, among which metabolic dysfunction-associated liver disease and chronic viral hepatitis are the two major drivers worldwide. However, the molecular mechanisms linking metabolic stress to HCC progression remain incompletely understood. Dynamin-1 (DNM1), primarily known for its role in vesicular trafficking, has emerged as a potential oncogene, yet its prognostic and functional significance in HCC remains largely unexplored. Here, we investigated the role of DNM1 in high-fat diet (HFD)-associated hepatocarcinogenesis. Transcriptomic profiling was conducted to identify differentially expressed genes between normal and high-fat diet murine models, with human orthologs mapped. Clinical relevance was validated using The Cancer Genome Atlas (TCGA-LIHC) dataset. Survival analysis, GSEA (Gene Set Enrichment Analysis), and subgroup stratifications based on viral hepatitis status were performed. <i>In vitro</i>, loss-of-function assays (shRNA knockdown) were executed in HepG2 and SK-Hep1 cell lines to assess cell viability and migration. DNM1 was significantly upregulated in high-fat diet models. In the TCGA-LIHC cohort, high DNM1 expression was an independent risk factor for poor overall survival (HR=1.44, P=0.039) and correlated with advanced tumor stages (Stage III+IV, P=0.010). In vitro knockdown of DNM1 profoundly impaired cell proliferation and migration in HCC cell lines. Strikingly, DNM1 expression was further elevated in patients with concurrent viral hepatitis (P=0.009). GSEA revealed that high DNM1 expression was positively associated with viral infection pathways and negatively correlated with critical immune responses, including interferon-alpha/gamma responses and host immune cytolysis. Survival analysis stratified by four subgroups demonstrated that patients with both viral infection and high DNM1 expression exhibited the worst prognosis (Overall Log-rank P < 0.001). Our findings identify DNM1 as a high-fat diet-responsive regulator that links metabolic stress to hepatocellular carcinoma progression. Elevated DNM1 expression promotes malignant phenotypes in HCC and identifies a subgroup of viral-associated patients with particularly poor prognosis, highlighting DNM1 as a potential prognostic biomarker and therapeutic target.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3476-3487"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928609","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}
Dejun Fan, Ruirui Niu, Feiyue Zhou, Li Yang, Chunmei Zhang
{"title":"Incremental value of prostate-specific antigen density beyond PI-RADS and conventional MRI features for predicting the highest ISUP grade group in patients with prostate cancer diagnosed at initial systematic prostate biopsy.","authors":"Dejun Fan, Ruirui Niu, Feiyue Zhou, Li Yang, Chunmei Zhang","doi":"10.62347/BHOD8380","DOIUrl":"10.62347/BHOD8380","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the incremental value of prostate-specific antigen density (PSAD) beyond the Prostate Imaging Reporting and Data System (PI-RADS) score and conventional magnetic resonance imaging (MRI) features for predicting the highest International Society of Urological Pathology (ISUP) grade group at initial systematic biopsy.</p><p><strong>Methods: </strong>This retrospective study included 171 patients with prostate cancer diagnosed by initial systematic biopsy between February 2022 and February 2026. All patients underwent 3.0-T multiparametric MRI within 15 days before biopsy. The highest ISUP grade group across all biopsy cores was the primary outcome. A baseline model, an MRI-extended model, and a combined model incorporating PSAD were sequentially developed using proportional odds ordinal logistic regression. Internal validation was performed with 2,000 bootstrap resamples. Firth logistic regression and sensitivity analyses were used to assess robustness.</p><p><strong>Results: </strong>The numbers of patients with ISUP grade groups 1-5 were 26, 10, 9, 40, and 86, respectively; 135 patients (78.9%) had grade group ≥3. Median PSAD increased from 0.20 ng/mL<sup>2</sup> in grade group 1 to 1.38 ng/mL<sup>2</sup> in grade group 5 (P<0.001). After adjustment for age, PI-RADS score, MRI-suspected local progression, and multizonal involvement on MRI, each doubling of PSAD was associated with higher ISUP grade group (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.59-2.62; P<0.001). Adding PSAD significantly improved model fit (likelihood ratio χ<sup>2</sup>=37.83; P<0.001) and increased the bootstrap-corrected ordinal C-statistic from 0.660 to 0.744. Paired out-of-bag analysis showed a median increase of 0.094 in the ordinal C-statistic (95% CI, 0.012-0.171). The combined model achieved an out-of-bag area under the receiver operating characteristic curve of 0.835 for grade group ≥3. The association remained robust after excluding patients with total prostate-specific antigen >100 ng/mL (OR, 2.36; 95% CI, 1.68-3.29) and among patients with PI-RADS scores ≤3 (OR, 2.60; 95% CI, 1.46-5.58; P<0.001).</p><p><strong>Conclusions: </strong>PSAD was independently associated with the highest biopsy ISUP grade group and provided incremental predictive information beyond PI-RADS and conventional MRI features. PSAD may also aid in identifying patients with low PI-RADS scores but high pathological grade groups, although external validation is required.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3694-3709"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928676","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}