International Journal of Cancer最新文献

{"title":"Plasma PlGF as a Potential Biomarker in Ramucirumab-Based Second-Line Therapy for Advanced Gastroesophageal Adenocarcinoma: Exploratory Biomarker Analysis from the Phase II Part of the RAMIRIS Trial.","authors":"Jurek Hille, Sylvie Lorenzen, Claudia Pauligk, Victoria Gensch, Peter Thuss-Patience, Eray Goekkurt, Thomas Ettrich, Florian Lordick, Carsten Bokemeyer, Christian Müller, Peter Reichardt, Martin Sökler, Daniel Pink, Stefan Probst, Thorsten O Goetze, Salah E Al-Batran, Sonja Loges, Melanie Janning","doi":"10.1002/ijc.70567","DOIUrl":"10.1002/ijc.70567","url":null,"abstract":"<p><p>Antiangiogenic treatment with ramucirumab (RAM) is a standard second-line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5-fluororuracil, leucovorin and irinotecan) in this setting. We present the exploratory biomarker analysis evaluating placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase. Plasma samples from 99 patients enrolled in RAMIRIS were collected at predefined timepoints (baseline, Cycle 2 Day 1, and Cycle 4 Day 1). PlGF, CAIX, and tryptase were quantified by ELISA. Associations with progression-free survival (PFS) and overall survival (OS) were analyzed using dichotomized biomarker levels and Cox regression models. PlGF levels increased substantially under treatment, whereas CAIX showed a transient rise, followed by a slight decline, and tryptase remained stable. Elevated PlGF levels at baseline and early-treatment (c2d1) were associated with shorter OS in univariate analysis (baseline HR_u = 1.75; p = 0.020; c2d1 HR_u = 1.69; p = 0.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HR_m = 1.41, p = 0.198; c2d1 HR_m = 1.85, p = 0.030). CAIX and tryptase showed no consistent associations with survival. Elevated PlGF-particularly its early increase during RAM-based therapy-was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis-generating and require validation in independent biomarker-driven studies.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1817-1828"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Protein Biomarkers Outperform Bacterial Proteins in Colorectal Cancer Detection.","authors":"Roza C M Opperman, Sofie Bosch, Alex A Henneman, Thang V Pham, Sander R Piersma, Tim G J de Meij, Meike de Wit, Beatriz Carvalho, Remond J A Fijneman, Gerrit A Meijer, Evelien Dekker, Connie R Jimenez, Nanne K H de Boer","doi":"10.1002/ijc.70760","DOIUrl":"https://doi.org/10.1002/ijc.70760","url":null,"abstract":"<p><p>Colorectal cancer (CRC) generally develops from precancerous adenomatous lesions, including advanced adenomas (AA), through a sequence of carcinogenic molecular alterations. The composition of the gut microbiota and the fecal proteome is known to differ between individuals with AA and CRC compared to controls, providing opportunities for biomarker discovery. This study aims to assess the potential of bacterial proteins as non-invasive biomarkers alone or in combination with human proteins. Therefore, two fecal sample sets from a colonoscopy-controlled population were analyzed: sample set 1 (CRC: 12, AA: 10, controls: 20) and sample set 2 (CRC: 79, AA: 40, controls: 129). Mass spectrometry-based proteomics was used to identify and quantify proteins in the fecal samples of the two series. Overlapping differential proteins (p < 0.05) were used to establish biomarker panels through logistic regression and leave-one-out cross-validation. Three biomarker panels were evaluated: one containing bacterial proteins, one combining human and bacterial proteins, and one containing human proteins alone. In total, 5400 overlapping proteins were identified across both sample sets. For combined CRC and advanced adenoma detection, the human-bacterial and human-only panels achieved the best performance (AUCs 0.88-0.90; sensitivities 56%-68%), exceeding human hemoglobin alone (AUCs 0.78-0.86; sensitivity 49%) and the bacterial panel (AUCs 0.67-0.75; sensitivities 17%-46%). In conclusion, human protein biomarker panels demonstrate superior diagnostic performance over bacterial proteins, particularly for CRC detection, indicating that the diagnostic value of fecal metaproteomics in this setting is mainly driven by host-derived proteins.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Serum lncRNA Signature Determines Oncogenic YAP Activity in Cancer Patients.","authors":"Fabian Rose, Nada El-Ekiaby, Lilija Wehling, Sofia Maria Elisabeth Weiler, Jennifer Schmitt, Marcell Tóth, Fabiola Pedrini, Amruta Damle-Vartak, Carsten Sticht, Rossella Pellegrino, Injie Omar Fawzy, Merna Hatem Mohamed Hamad, Mohamed Negm, Dina Omar, Hossam Eldeen Soliman, Gamal Esmat, Thomas Longerich, Thomas Illig, Bruno Christian Köhler, Anna Saborowski, Heike Bantel, Arndt Vogel, Peter Schirmacher, Ahmed Ihab Abdelaziz, Kai Breuhahn","doi":"10.1002/ijc.70584","DOIUrl":"10.1002/ijc.70584","url":null,"abstract":"<p><p>Biomarkers are typically identified by comparing human samples such as tissues and serum. However, reliable markers for transcriptionally active oncogenes remain elusive due to tumor heterogeneity and confounding signals from non-tumorous cells. We hypothesize that in vitro screening is sufficient to identify a long non-coding RNA (lncRNA) signature that is a specific marker for oncogenic transcriptional regulators. Exemplified for the Hippo pathway effectors, we integrated experimental NGS and cancer patient expression data with bioinformatics approaches to identify a yes-associated protein (YAP)-specific lncRNA signature in hepatocellular carcinoma (HCC) cells. The lncRNAs in this signature include CYTOR, MIR4435-2HG, SNHG1, and SNHG17, which partly promote HCC cell proliferation and control the sensitivity to YAP/TEA domain transcription factor (TEAD)-targeted inhibition. In HCC tissues, the lncRNA signature is associated with increased nuclear enrichment of YAP, the expression of YAP target genes, and poor clinical outcomes in patients. This association was also confirmed in cells and tissues of other malignancies, including lung adenocarcinoma (LUAD). Notably, the lncRNA signature is detectable in the serum of HCC patients and predicts YAP activation in tumor tissues. In summary, the Hippo pathway-associated lncRNA signature provides a readout for oncogenic YAP activity across cancers, suggesting its potential as a pan-cancer biomarker. Our results highlight oncogene-specific lncRNA signatures as valuable tools for diagnostics, therapy selection, and treatment monitoring.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1829-1843"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRCA1/2 Carriers With Breast-Ovarian Double Primary Cancers Versus Ovarian Cancer Alone: Mutation Profiles and Survival Outcomes.","authors":"Tongxia Wang, Dan Zhao, Yuelin Song, You Wu, Yiming Fan, Manqi Wu, Cuiyu Huang, Yan Liu, Yan Zhang, Xielan Yang, Zhumei Cui, Yuanjing Hu, Yuan Li, Hongyan Guo, Yuntao Xie, Qiyu Liu","doi":"10.1002/ijc.70759","DOIUrl":"https://doi.org/10.1002/ijc.70759","url":null,"abstract":"<p><p>Germline pathogenic variants in BRCA1/2 substantially increase lifetime risks of both breast and ovarian cancers. However, whether specific mutation characteristics predispose carriers to breast-ovarian double primary cancers (DPC) and whether DPC affects ovarian cancer outcomes-particularly in the PARP inhibitor (PARPi) era-remain unclear. We conducted a retrospective analysis of patients with germline BRCA1/2-mutated high-grade serous ovarian cancer in China from 2015 to 2025, including 114 DPC patients and 296 ovarian cancer (OC)-only patients as controls. Clinical characteristics, mutation profiles, and survival outcomes were compared between the two groups. Among 114 DPC patients, 92 were diagnosed with breast cancer first, 12 with ovarian cancer first, 9 had synchronous diagnoses, and 1 was unknown. Compared with the OC-only group, BRCA1/2 mutations in the DPC group were predominantly located outside the Ovarian Cancer Cluster Region (BRCA1: 63.1% vs. 48.9%, p = 0.019; BRCA2: 80.0% vs. 56.2%, p = 0.008). Among BRCA2-mutated patients, DNA-binding domain mutations were enriched in the DPC group (33.3% vs. 17.8%, p = 0.018). Both groups benefited from first-line PARPi maintenance. No significant differences in progression-free or overall survival were observed between DPC and OC-only patients on either univariable or multivariable analysis. A subgroup analysis restricted to the 92 patients whose breast cancer preceded ovarian cancer yielded consistent results. In conclusion, the location of BRCA1/2 mutations influences susceptibility to breast-ovarian DPC. DPC status was not significantly associated with inferior survival in this cohort; however, long-term outcomes warrant validation in larger, prospectively followed populations.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comments on \"Prior Immunotherapy Enhances Survival Outcomes of Third-Line Apatinib Treatment in Advanced Gastric Cancer: A Retrospective Cohort Study\".","authors":"Heng Xu, Jiaan Lu","doi":"10.1002/ijc.70568","DOIUrl":"10.1002/ijc.70568","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":"1844-1845"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148012871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Comparisons of Blood, Upper Respiratory Tract and Gut Viromes From Patients With Lung Cancer and Healthy Persons\".","authors":"","doi":"10.1002/ijc.70756","DOIUrl":"https://doi.org/10.1002/ijc.70756","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Term PM2.5 Exposure and Daily Cancer Mortality Across 47 Japanese Prefectures: A Nationwide Time-Stratified Case-Crossover Study, 2013-2022.","authors":"Tshewang Gyeltshen, Aminu Kende Abubakar, Hassan Jamil, Takao Suzuki, Hellen Babu, Phuong The Nguyen","doi":"10.1002/ijc.70761","DOIUrl":"https://doi.org/10.1002/ijc.70761","url":null,"abstract":"<p><p>Short-term exposure to fine particulate matter (PM2.5) is an established risk factor for cardiopulmonary mortality, but its acute association with cancer mortality remains poorly characterized. We examined associations between short-term PM2.5 fluctuations and daily all-cancer and site-specific mortality across all 47 Japanese prefectures from January 1, 2013, to December 31, 2022. Using a nationwide time-stratified case-crossover design, we fitted prefecture-specific conditional quasi-Poisson regression models and pooled the estimates by random-effects meta-analysis, expressing associations as the excess relative risk (ERR) per 10 μg/m³ increase in PM2.5 (lag 0-2 days). Sensitivity analyses varied lag structures, meteorological spline specifications, and co-pollutant adjustment. A 10 μg/m³ increase in short-term PM2.5 was associated with a 0.88% increase in all-cancer mortality (95% CI: 0.57-1.18; p < 0.001). The association was consistent across sex, age, and primary site (all interaction p > 0.40), with significant estimates for breast (ERR 2.06%), colorectal (1.06%), stomach (0.81%), and lung (0.77%) cancers. Associations attenuated with longer moving-average windows and were no longer statistically significant from lag 0-5 onward. A measurable fraction of cancer deaths was attributable to PM2.5 above the WHO 24-h guideline (15 μg/m³), with the largest fractions tracking prefecture-specific coefficients rather than ambient concentration. These findings indicate that short-term PM2.5 exposure is associated with higher daily mortality across diverse cancer types in Japan, even at relatively low ambient levels. Because the individual-level effect size is small and attenuated to non-significance after adjustment for either NO₂ or SO₂, these findings are best interpreted as supporting population-level air-quality measures rather than individual clinical intervention.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Design and Initial Findings of a Natural History Study of Anal HPV and Associated Lesions Among Young Adult Women in Costa Rica\".","authors":"","doi":"10.1002/ijc.70757","DOIUrl":"https://doi.org/10.1002/ijc.70757","url":null,"abstract":"","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Phase II Study of Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma (NEOFOL).","authors":"Attapol Titapun, Aumkhae Sookprasert, Kosin Wirasorn, Piyakarn Watcharenwong, Thanachai Sanlung, Vor Luvira, Tharatip Srisuk, Apiwat Jarearnrat, Vasin Thanasukarn, Julaluck Promsorn, Kulyada Somsap, Prin Twinprai, Piya Prajumwongs, Watcharin Loilome, Jarin Chindaprasirt","doi":"10.1002/ijc.70758","DOIUrl":"https://doi.org/10.1002/ijc.70758","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) has poor outcomes despite curative-intent surgery. Neoadjuvant chemotherapy may improve tumor response and resectability. This study evaluated the efficacy and safety of neoadjuvant modified FOLFOXIRI (mFOLFOXIRI) in patients with potentially resectable CCA. In this prospective, single-arm, phase II study, 25 patients with potentially resectable cholangiocarcinoma received six cycles of neoadjuvant mFOLFOXIRI every 2 weeks. Surgical resection was performed when feasible. The primary endpoint was objective response according to RECIST version 1.1. Secondary endpoints included resectability, R0 resection, recurrence-free survival (RFS), overall survival (OS), safety, and health-related quality of life assessed using EQ-5D-5L. The objective response rate was 44.0%, with partial response in 11 patients, stable disease in 10 patients, and progressive disease in four patients. After neoadjuvant therapy, 20 patients (80.0%) were considered resectable, and 16 (64.0%) underwent curative-intent resection, with an R0 resection rate of 75.0%. Major pathological response occurred in two patients (12.5%). Among resected patients, seven (43.8%) had recurrence, with a median RFS of 18.93 months. The median OS in the overall cohort was 26.70 months. In unadjusted Kaplan-Meier analyses, radiologic response and surgical resection were significantly associated with longer overall survival. Grade 3-4 neutropenia occurred in 36.0% of patients, and no treatment-related deaths occurred. Health-related quality of life remained generally stable during treatment. Neoadjuvant mFOLFOXIRI showed promising antitumor activity, enabled a high rate of curative-intent resection, and demonstrated manageable toxicity in patients with potentially resectable cholangiocarcinoma. These findings support further investigation of this regimen as a neoadjuvant treatment strategy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Predictors of Smoking: External Validation and Association With Smoking-Related Cancer Risk.","authors":"Xiaoyu Fan, Danmeng Lily Li, Allison M Hodge, Julie K Bassett, Nina Afshar, Melissa C Southey, Graham G Giles, Roger L Milne, Pierre-Antoine Dugué","doi":"10.1002/ijc.70755","DOIUrl":"https://doi.org/10.1002/ijc.70755","url":null,"abstract":"<p><p>Tobacco smoking has a strong influence on DNA methylation (DNAm), enabling the development of DNAm-based smoking predictors, yet external evaluations of these have remained limited. We aimed to assess six DNAm-based smoking predictors in a large sample of middle-aged and older Australians for (i) their accuracy and reliability, and (ii) their association with risk of smoking-related cancers. We used blood DNAm data from the Melbourne Collaborative Cohort Study to calculate six DNAm-based smoking predictors (EpiSmokEr, Elliott-183, McCartney-233, DNAmPACKYEARS, PCPACKYEARS, and mCigarette). Accuracy with respect to self-reported smoking pack-years (N = 2875, median age: 61 years) was assessed using Pearson's correlations, explained variance, and area under the curve (AUC). Reliability was assessed using intraclass correlation coefficients (ICCs) in 364 duplicated samples. Conditional logistic regression was used to assess associations with lung (N_cases = 332) and urothelial (N_cases = 426) cancer risk in two nested case-control studies. All smoking predictors showed excellent reliability (ICC > 0.9) and ability to distinguish current from never smokers (AUCs: 0.94-0.98), explaining 35%-50% variance of smoking pack-years. The predictors were positively associated with smoking-related cancer risk, with strongest adjusted associations observed for mCigarette with lung cancer (per SD, rate ratio [RR] = 2.18, 95% CI: 1.57-3.02) and for PCPACKYEARS with urothelial cancer (RR = 1.62, 95% CI: 1.27-2.07). This translated into prediction gains compared with models solely based on questionnaire-collected smoking variables. In middle-aged and older Australians, DNAm-based smoking predictors showed very good reliability and accuracy in predicting smoking exposure, and strong positive associations with smoking-related cancer risk beyond self-reported smoking information. This highlights their potential utility as an alternative or addition to self-reported smoking information for cancer risk stratification.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}