American journal of cancer research最新文献

{"title":"Serum inflammatory markers and influencing factors in patients with colorectal adenomas.","authors":"Linjin Chen, Haiyan Zhong, Zijie Wang, Xingxing Zhang, Yan Li","doi":"10.62347/PPEI1509","DOIUrl":"10.62347/PPEI1509","url":null,"abstract":"<p><p>This study aimed to investigate the expression patterns of serum inflammatory markers (SIMs) in patients with colorectal adenomas (CRAs) and identify the associated influencing factors. A total of 420 patients who underwent colonoscopy between January 2020 and December 2025 were included in this study. Patients with colonoscopy-identified CRAs were assigned to the CRA group (n=285), whereas individuals without obvious endoscopic abnormalities served as the control group (n=135). SIMs, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as blood lipids, including total cholesterol (TC), triglyceride (TG), and high-/low-density lipoprotein cholesterol (HDL-C/LDL-C), were measured and compared between the two groups. CRA patients presented with higher TG levels, lower HDL-C levels, and elevated SIM levels compared with controls (P<0.05). Univariate analysis revealed significant between-group differences in age, smoking history, drinking history, hepatic steatosis, cholecystic polyps, gallstones, TG, and HDL-C. Logistic regression analysis demonstrated that older age, smoking, hypertriglyceridemia, low HDL-C levels, and elevated inflammatory marker levels were independent risk factors for CRAs. In conclusion, smoking, dyslipidemia, and chronic inflammation are independent factors associated with CRA development. In addition to lifestyle modification and lipid management, dynamic monitoring of inflammatory markers may have important clinical value for improving the early identification of individuals at high risk of CRAs.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3516-3525"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928605","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":"Transcriptional activation of ALOX5 by c-Myc drives malignant progression and M2 macrophage polarization in clear cell renal cell carcinoma.","authors":"Changjie Ren, Yijun Tian, Xinran Zhang, Denglong Wu, Weidong Zhou, Xue Zhang","doi":"10.62347/CRGB4288","DOIUrl":"10.62347/CRGB4288","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy with poor prognosis, but the molecular mechanisms linking oncogenic signaling to macrophage polarization remain unclear. In this study, we identify arachidonate 5-lipoxygenase (ALOX5) as an oncogenic factor in ccRCC. Multi-omics analyses and clinical validation show that ALOX5 is up-regulated in ccRCC tissues and its high expression is associated with advanced tumor stage and poor survival. Functional assessments reveal that silencing ALOX5 in ccRCC cells inhibits cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) <i>in vitro</i>, and suppresses tumor progression <i>in vivo</i>. Notably, ALOX5 expression in ccRCC cells is positively correlated with the polarization of infiltrating macrophages into the M2 phenotype, and the accumulation of this portion of M2-polarized tumor-associated macrophages (TAMs) in the tumor microenvironment. ALOX5 knockdown reduces macrophage migration and M2 marker expression. Mechanistically, c-Myc directly binds to the ALOX5 promoter and activates its transcription. Restoration of ALOX5 in c-Myc-silenced cells partially rescues the malignant phenotype and M2 polarization, confirming a functional c-Myc-ALOX5 axis. Collectively, our findings suggest that the c-Myc-ALOX5 pathway promotes ccRCC progression by enhancing tumor cell aggressiveness and M2 macrophage polarization, offering a potential therapeutic target for immune microenvironment modulation in renal cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3644-3659"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928643","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":"Advances in nanotechnology for early cancer diagnosis: emerging nanoplatforms and multimodal imaging approaches.","authors":"Yuxin Mao, Muhammad Jamil, Dianhui Yang","doi":"10.62347/FJBG4765","DOIUrl":"10.62347/FJBG4765","url":null,"abstract":"<p><p>Nanotechnology has revolutionized the field of cancer diagnosis, by enabling the development of innovative platforms for diagnosis that offer the potential to identify malignancies at an early stage, and they possess an unprecedented degree of sensitivity and specificity. This review focuses on the combination of nanotechnology and different imaging modality such as magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) and optical imaging which demonstrate the potential to target tumour with high precision. We delve into the physicochemical characteristics of nanoparticles such as size, surface charge and functionalization that allow nanoparticles to cross the biological barriers, preferentially accumulate in tumor sites and deliver diagnostic and therapeutic payloads. Special attention is paid to the achievements in multimodal and theranostics platforms, where a single nanoparticle is able to perform both imaging and therapy at the same time. While these have great potential, there are challenges with clinical translation of these technologies ranging from biodistribution, toxicity, immunogenicity and regulatory hurdles. Despite these hurdles the accumulating amount of clinical evidence indicates that nanotechnology will have a significant role in precision oncology that will move from the experimental stages to routine clinical use, thus changing the paradigms of cancer detection and treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3222-3253"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928710","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":"Dual role of HIF-1α in gliomas: enhancing COX7A2 degradation and SCAF1 expression for ATP production and tumor progression.","authors":"Minfang Lai, Wenping Feng, Jinyou Ouyang, Jianguo Kuang, Shengze Deng","doi":"10.62347/RIKY8807","DOIUrl":"10.62347/RIKY8807","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether HIF-1α promotes SCAF1/COX7A2 replacement in complex IV and thereby influences glioma progression.</p><p><strong>Methods: </strong>A172 and U251 cells were subjected to CoCl₂-induced hypoxia. The effects of hypoxia on cell behavior were assessed via CCK-8 for viability and Transwell for migration and invasion. Stable cell lines overexpressing HIF-1α, SCAF1, or CLPP, or knocking down COX7A2, LONP1, or CLPP were established. Mitochondrial supercomplex composition was analyzed by Blue Native PAGE. HIF-1α's binding to the SCAF1 promoter was validated by ChIP and dual-luciferase assays. Protein interactions were examined by Co-IP and GST pull-down. Xenograft tumor growth experiments conducted in nude mice was evaluated following COX7A2 overexpression or SCAF1 knockdown in tumor growth.</p><p><strong>Results: </strong>CoCl₂ treatment significantly increased cell viability, migration, invasion, ATP concentration and the formation of I+III₂+IV of glioma cells, and similar effects were observed upon HIF-1α overexpression, COX7A2 knockdown, or SCAF1 overexpression. HIF-1α targeted the SCAF1 promoter to regulate its expression, and HIF-1α regulated COX7A2 protein levels through LONP1 and CLPP. In the tumorigenesis experiment in nude mice, SCAF1 knockdown reduced tumor volume and weight, while COX7A2 overexpression reduced tumor volume and weight.</p><p><strong>Conclusion: </strong>Hypoxia in glioma cells enhances cell viability, migration, invasion, ATP production, and I+III₂+IV supercomplex formation, with HIF-1α regulating SCAF1 and COX7A2 levels. These findings highlight the promising potential of targeting the HIF-1α/SCAF1/COX7A2 pathway as a treatment option for glioma treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3338-3358"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928837","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":"Research advances in single-molecule multi-target strategies targeting ferroptosis for colorectal cancer treatment.","authors":"Zirui Weng, Yingting Zhu, Weirong Yin, Jingyu Zhang, Luohang Ni, Xueting Deng, Lin Miao","doi":"10.62347/KLUJ3717","DOIUrl":"10.62347/KLUJ3717","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a highly prevalent malignancy worldwide, with its incidence and mortality continuing to rise, and with an emerging trend toward younger-onset disease. The efficacy of current treatment modalities, including surgery, chemotherapy, targeted therapy, and immunotherapy, is often limited by the development of drug resistance. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is governed by a sophisticated regulatory network comprising core pathways and bypass systems in CRC, offering numerous potential targets for therapeutic intervention. The single-molecule multi-target strategy employs a single compound to simultaneously act upon multiple key nodes within this network, circumventing the resistance commonly associated with single-target agents while avoiding the pharmacokinetic interactions and additive toxicities of drug combinations. This review systematically delineates the key pathways and core targets of ferroptosis in CRC and summarizes recent progress across three classes of single-molecule multi-target compounds: natural products, synthetic small molecules, and \"one-drug multi-modal death\" inducers. We further propose a drug development and design framework integrating structural optimization, target integration, and delivery efficiency. Finally, we discuss current challenges and future directions, aiming to provide a theoretical foundation for developing novel CRC treatment strategies.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3319-3337"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928663","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":"Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.","authors":"Winifer Ali, Christina Nadolny, Xinmu Zhang, Qiwen Chen, Syed F Hashmi, Tasneem Huniti, Md Mosiqur Rahman, Lia Bozza, Danielle Warila, Ruitang Deng","doi":"10.62347/UIYZ8333","DOIUrl":"10.62347/UIYZ8333","url":null,"abstract":"<p><p>Farnesoid X receptor (FXR) signaling plays an important role in liver regeneration and carcinogenesis. Dysregulation of FXR signaling is linked to the pathogenesis of hepatocellular carcinoma (HCC) while FXR knockout mice spontaneously develop HCC as they age. Ubiquitin specific peptidase 2b (USP2b) is a deubiquitinating enzyme regulating protein stability and other activities. In our recent study, we found that USP2b was significantly downregulated in subjects with HCC and exhibited both tumor-promoting and tumor suppressive activity in a context-dependent manner. However, the mechanistic link between FXR signaling and USP2b and its implications in the pathogenesis of HCC remain to be determined. In this study, we revealed that USP2b was transcriptionally regulated by FXR. Activation of FXR significantly increased while antagonizing FXR reduced USP2b mRNA and protein expression <i>in vitro</i> and <i>in vivo</i>. Consistently, USP2b expression was significantly reduced in FXR knockout (FXR-KO) mice. Further investigation showed that USP2b was transcriptionally regulated by FXR in an isoform-specific manner, predominantly by FXRα2 but not FXRα1. The transcription starting sites (TSS) of USP2 isoforms were determined by 5'RACE, which leads to the identification of the USP2b-specific promoter. An FXR response element (FXRE) was identified in the USP2b promoter and functionally characterized. FXR directly bound to the FXRE <i>in vitro</i> and recruited to the USP2b promoter in intact cells and <i>in vivo</i>. Further study revealed that upon FXR activation, co-activator-associated arginine methyltransferase 1 (CARM-1) was significantly recruited to the human USP2b promoter while coactivators glutamate receptor-interacting protein 1 (GRIP-1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) were significantly recruited to the mouse USP2b promoter. Over-expression of USP2b in FXR-KO mice significantly slowed down tumor growth with reduced tumor size while maintained comparable tumor numbers consistent with its tumor suppressive activity. In summary, this study demonstrated that USP2b was transcriptionally regulated by FXR in an isoform-dependent manner and USP2b played a tumor-suppressive role in the pathogenesis of FXR deficiency-induced HCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3660-3677"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928613","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":"Perioperative ΔNLR and ΔPNI independently predict postoperative pulmonary complications in non-small cell lung cancer: a difference analysis-based nomogram.","authors":"Shen Zhou, Wanan Dai, Min Huang","doi":"10.62347/ITFT9660","DOIUrl":"10.62347/ITFT9660","url":null,"abstract":"<p><p>This study investigated whether perioperative dynamic changes in inflammatory and immunonutritional markers could predict postoperative pulmonary complications (PPCs) in non-small cell lung cancer (NSCLC). We retrospectively enrolled 550 NSCLC patients who underwent radical resection, randomly split at a 7:3 ratio into training (n = 384) and validation (n = 166) sets. PPCs occurred in 126 patients (22.91%), with pneumonia being the most common type. Perioperative ΔWBC, ΔNLR, ΔPLR, ΔCAR, ΔLCR, ΔAGR, and ΔPNI were calculated as the values on postoperative day 1 minus the preoperative values. Through univariate screening, Spearman correlation analysis, variance inflation factor testing, LASSO regression, and multivariate logistic regression, five independent predictors were identified: age, lobectomy, number of lymph nodes dissected, ΔNLR, and ΔPNI. A nomogram incorporating these variables was constructed, achieving an AUC of 0.888 (95% CI: 0.843-0.934) in the training set and 0.887 (95% CI: 0.831-0.942) in the validation set, outperforming the ARISCAT score and single ΔPNI. Calibration was satisfactory (validation set Hosmer-Lemeshow test, P = 0.897; Brier score, 0.106), and decision curve analysis confirmed clinical net benefit. Risk stratification using the nomogram cutoff (0.23) effectively discriminated high-risk patients with significantly worse clinical outcomes. Subgroup and sensitivity analyses demonstrated robust predictive stability without obvious overfitting. The nomogram integrating perioperative ΔNLR and ΔPNI provides a practical tool for early identification and risk stratification of PPCs after NSCLC surgery.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3574-3600"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928610","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":"Association between DPAGT1 and Siglec-15 expression and the malignant phenotype of hepatocellular carcinoma.","authors":"Min Luo, Xiaochen Wang, Hongzhi Wang, Yanping Liu, Chaoyuan Huang, Haotang Wei","doi":"10.62347/UYRE7518","DOIUrl":"10.62347/UYRE7518","url":null,"abstract":"<p><p>N-acetylglucosamine phosphotransferase 1 (DPAGT1), a key enzyme involved in protein glycosylation, has been implicated in tumor progression; however, its relationship with sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) in hepatocellular carcinoma (HCC) remains unclear. This study investigated the association between DPAGT1 expression, Siglec-15 expression, and malignant phenotypes in HCC. Bioinformatic analysis of the GEPIA database revealed higher expression of DPAGT1 and Siglec-15 in HCC tissues. Higher DPAGT1 expression was associated with poorer overall survival, whereas Siglec-15 expression showed no significant association with survival outcomes. Although DPAGT1 and Siglec-15 expression levels showed a statistically significant correlation, the correlation strength was weak. Functional experiments demonstrated that DPAGT1 overexpression promoted proliferation, migration, and invasion of HCC cells, whereas DPAGT1 knockdown resulted in reduced malignant phenotypes. Re-expression of Siglec-15 partially alleviated the inhibitory effects associated with DPAGT1 depletion. Similar alterations were observed in Hep-3B cells and a xenograft model, where DPAGT1 modulation was associated with changes in tumor growth, Siglec-15 expression, TGF-β1 levels, AKT phosphorylation, and EMT-related molecular markers. Collectively, these findings suggest that DPAGT1 may contribute to HCC progression and is functionally associated with Siglec-15 expression and EMT-related molecular alterations. Further studies are required to clarify the underlying molecular relationship between DPAGT1 and Siglec-15.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3408-3421"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928798","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":"Establishment an early precise diagnosis model for bone metastasis in lung cancer based on driver gene types.","authors":"Sen Cao, Lu Bai, Yuehua Zhang, Wen Li, Zheng Wu, Xing Li, Jinyue Li, Chunwang Yang, Zhiyu Wang","doi":"10.62347/UOUD9807","DOIUrl":"10.62347/UOUD9807","url":null,"abstract":"<p><p>Lung cancer has become the type of cancer with the highest incidence rate and the greatest threat of death worldwide. Bone is one of the common distant metastasis sites of lung cancer. Once a patient experiences bone metastasis, it will seriously affect the patient's quality of life and survival period. This study aimed to investigate the impact of driver gene mutations on the anatomical distribution patterns of BM in lung cancer and develop a prediction model for specific BM sites of lung cancer. From 2019 to 2023, we enrolled 353 lung cancer patients diagnosed with BM at our hospital. Associations between driver gene types and BM sites or timing were analyzed using chi-square. A predictive model was constructed through logistic regression, and its performance was evaluated using AUC, DCA, calibration curves, and independent cohort validation. The research found that driver gene types were significantly associated with the risk of simultaneous pelvic metastasis (P < 0.001). Logistic regression analysis identified five independent risk factors for simultaneous pelvic metastasis in lung cancer. The model demonstrated good predictive performance, with AUC values of 0.881 in the training set and 0.816 in the validation set. This study presents a novel analysis of the relationship between driver gene types and the spatio-temporal patterns of BM. Based on driver gene types, we developed an accurate nomogram model for predicting BM in lung cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3601-3619"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928675","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":"Dynamic changes in D-dimer during first-line therapy and their association with overall survival in advanced lung cancer: a retrospective study.","authors":"Xiaoqiang Ye, Chengying Xu, Liyang Yu, Bicui Zhan","doi":"10.62347/VZHI7640","DOIUrl":"10.62347/VZHI7640","url":null,"abstract":"<p><p>This study investigated the association between dynamic changes in D-dimer (D-D) during first-line systemic therapy and overall survival (OS) in patients with advanced lung cancer (LC). We also evaluated the independent prognostic value of these dynamic changes after adjusting for confounders and other coagulation markers. This retrospective study included patients with advanced LC who received first-line systemic therapy between January 2018 and December 2023. The percentage change in D-D from baseline to 3 months was calculated. A 3-month landmark analysis was used to reduce immortal time bias. We fitted multivariable Cox proportional-hazards models adjusted for age, sex, disease stage, histology, liver metastasis, and additional confounders (thrombosis history, hypertension, diabetes, chronic obstructive pulmonary disease [COPD], and anemia) to assess the independent association between D-D dynamics and OS. Combined models incorporating D-D, fibrinogen, and platelet data were also evaluated. Restricted cubic splines were utilized to validate the threshold selection. Model performance was evaluated using time-dependent receiver operating characteristic curves, calibration plots, and decision curve analysis. A nomogram for individualized prediction was derived from the combined model and internally validated by bootstrap calibration. Among 192 enrolled patients, the landmark cohort comprised 160 cases (median follow-up 32.5 months). The D-D increase group had a significantly shorter median OS than the stable groups (8.2 vs. 51.8 months) and the decrease group (median not reached; log-rank P < 0.001). After full adjustment, a marked D-D increase remained independently associated with a higher risk of death compared with the stable group (HR = 2.60, 95% CI: 1.44-4.71, P = 0.002), whereas a marked decrease showed a protective trend (HR = 0.56, 95% CI: 0.29-1.08, P = 0.084). The combined model that included D-D dynamics, fibrinogen changes, and platelet status achieved a C-index of 0.697, outperforming the D-D-only model (0.667) and the clinical-only model (0.592). Dynamic D-D changes are independently associated with OS in advanced LC during first-line treatment. The combined model, presented as a practical nomogram, offers a tool for individualized risk stratification; however, external multicenter validation is warranted.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 8","pages":"3542-3555"},"PeriodicalIF":3.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928852","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}