Molecular Oncology最新文献

{"title":"Engineered extracellular vesicles enriched with the miR-214/199a cluster enhance the efficacy of chemotherapy in ovarian cancer.","authors":"Weida Wang, Ayesha Alvero, Yi Qin, Mingjin Wang, Alexandra Fox, Yanfeng Li, Michael Millman, Amy Kemper, Gil Mor, Xian Shuang Liu, Michael Chopp, Zheng Gang Zhang, Yi Zhang","doi":"10.1002/1878-0261.70224","DOIUrl":"10.1002/1878-0261.70224","url":null,"abstract":"<p><p>Recurrent ovarian cancer (OC) remains a major cause of mortality due to chemoresistance and metastasis. Epigenetic aberrations, particularly dysregulated microRNA (miRNA) expression, contribute to disease progression and represent a promising therapeutic target. Here, we identify the miR-214-3p/miR-199a-5p cluster as a stage-associated, tumor-suppressive network that is lost in recurrent and chemoresistant OC but can be elevated using engineered small extracellular vesicles enriched with this miRNA cluster (m214-sEVs). Using a clinically relevant mouse model that recapitulates spontaneous OC relapse following platinum-based chemotherapy, we show that m214-sEVs are internalized by OC cells and niche fibroblasts, leading to increased intracellular levels of this cluster and suppression of key chemoresistance-associated pathways, including through downregulation of Toll-like receptor 4 (TLR4), β-catenin, and the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein YKT6. m214-sEV treatment reprograms secondary tumor-derived sEVs toward a less prometastatic cargo profile and decreases carboplatin resistance and cell migration. Enforced YKT6 overexpression abrogates these effects, establishing YKT6 as a key downstream effector. Collectively, these findings support engineered sEVs as a translatable strategy to overcome chemoresistance and disrupt pro-tumorigenic EV signaling in recurrent OC.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2220-2242"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181134","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":"CCDC80 suppresses high-grade serous ovarian cancer migration via negative regulation of B7-H3.","authors":"Aya Saleh, Nitzan Medina-Itzhaki, Milena Chekov, Eden Gal-Swisa, Roba Gabesh-Wahabi, Inbar Savyon, Inna Naroditsky, Hilary A Kenny, Basem Fares, Lina Korsensky, Einav Girsh, Liron Berger, Ruth Perets","doi":"10.1002/1878-0261.70235","DOIUrl":"10.1002/1878-0261.70235","url":null,"abstract":"<p><p>Paired box protein Pax-8 (PAX8) is a critical lineage marker and master regulator of transcription in high-grade serous ovarian carcinoma (HGSC)-the most common subtype of epithelial ovarian cancer-driving cell proliferation and migration and resisting apoptosis. This study aimed to elucidate the mechanism of action of PAX8 in this disease. By performing an unbiased analysis of PAX8-regulated genes, we discovered two PAX8-regulated genes-coiled-coil domain-containing protein 80 (CCDC80) and cluster of differentiation 276 (CD276) antigen (also known as B7-H3)-that mediate PAX8 activity and play key cancer cell autonomous roles in this disease. Our findings indicate that PAX8 negatively regulates CCDC80, a novel cell autonomous tumor suppressor in HGSC. We demonstrate that CCDC80, localized to the nucleus, significantly reduces HGSC tumor growth and metastasis in vivo in a mouse model. Notably, CCDC80 exerts its function by suppressing the expression of the immune checkpoint protein B7-H3. However, in HGSC, B7-H3 is predominantly cytoplasmic and promotes HGSC proliferation and migration independent of its immune role. Additionally, PAX8 positively regulates B7-H3 expression in a CCDC80-independent manner, underscoring the multifaceted oncogenic role of PAX8. This study highlights the complex regulatory network involving PAX8, CCDC80, and B7-H3 in HGSC progression. Targeting this signaling pathway may provide a novel therapeutic strategy to improve treatment outcomes for patients with epithelial ovarian cancer. B7-H3, which is currently targeted in clinical trials, shows promise as HGSC target for therapy.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2262-2279"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729389","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":"Tumor B-cell infiltration in platinum-treated advanced muscle-invasive urothelial carcinoma.","authors":"Konrad Stawiski, Júlia Perera-Bel, Alejo Rodriguez-Vida, Nuria Juanpere, Jihyun Lee, Daniel E Michaud, Jennifer L Guerriero, Kent W Mouw, Aristotelis Bamias, Filipe L F Carvalho, Joaquim Bellmunt","doi":"10.1002/1878-0261.70276","DOIUrl":"10.1002/1878-0261.70276","url":null,"abstract":"<p><p>Platinum chemotherapy is a standard therapeutic choice for advanced urothelial cancer, but biomarkers demonstrating its benefits are limited. We tested whether the tumor microenvironment, particularly B-cell infiltration, could predict overall survival after platinum chemotherapy. Pretreatment tumors from 189 patients in three cohorts treated with cisplatin- or carboplatin-based regimens underwent bulk transcriptome profiling. Immune cell infiltration and multicellular communities were inferred from gene expression and associated with overall survival using cohort-specific multivariable models and meta-analysis. Higher lymphocyte infiltration was associated with longer overall survival (hazard ratio 0.34, 95% confidence interval 0.16-0.72), driven by B cells and memory B cells (hazard ratio 0.19, 95% confidence interval 0.05-0.75). These associations were confined to cisplatin-treated patients and were strongest in tumors with a pro-inflammatory B-cell-rich community and concordant B-cell gene expression signatures. In contrast, higher myeloid infiltration was associated with shorter overall survival. Pretreatment B-cell enrichment in the tumor microenvironment identified a subset associated with improved overall survival among patients receiving platinum chemotherapy, particularly cisplatin, supporting B-cell-focused biomarker development and spatial characterization of tertiary lymphoid structures in urothelial cancer.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2340-2355"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143937","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":"Clinical performance of the urine-based TERT promoter AbsoluteQ Digital PCR for non-invasive detection of bladder cancer.","authors":"Anna Nykel, Izabela Kubiak, Lena Rutkowska, Żaneta Kasprzyk, Łukasz Kępczyński, Michał Bednarek, Dariusz Sobieraj, Jacek Wilkosz, Piotr Kania, Adam Jędrzejczyk, Bogdan Kałużewski, Agnieszka Gach, Tadeusz Kałużewski","doi":"10.1002/1878-0261.70262","DOIUrl":"10.1002/1878-0261.70262","url":null,"abstract":"<p><p>Bladder cancer (BC) is the ninth most common cancer worldwide, with urothelial carcinoma accounting for approximately 90% of all cases and presenting predominantly as non-muscle-invasive disease. Due to its high recurrence rate and the need for long-term surveillance, BC is associated with the highest lifetime treatment costs per patient among all cancers, making its effective management a significant clinical and economic challenge. The most frequently identified variants in the TERT gene promoter are c.-124C>T (C228T) and c.-146C>T (C250T), located within a region characterized by high guanine-cytosine (GC) content, which makes amplification challenging. We aimed to validate the AbsoluteQ Digital PCR assay for the detection of urine-based TERT promoter variants for the diagnosis of urothelial bladder cancer and to assess its diagnostic performance in comparison with standard methods. Urine samples were collected from patients with histopathologically confirmed bladder cancer (n = 58) and compared with a control group (n = 55). The C228T and C250T variants were tested using the AbsoluteQ Digital PCR assay. Sensitivity, specificity, and predictive values were calculated to evaluate the performance of the assessed method. The AbsoluteQ Digital PCR demonstrated superior diagnostic performance compared to conventional Sanger sequencing for detecting TERT promoter variants, achieving a sensitivity of 89.65% (95% CI: 78.16-95.72) and a specificity of 100% (95% CI: 91.87-100), with no false positives observed. Given its robustness and clinical relevance, AbsoluteQ Digital PCR is emerging as a promising tool for non-invasive molecular diagnostics targeting TERT promoter variants.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2163-2174"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840218","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":"Liquid biopsy-based diagnostic evaluation of hypermethylated CpG sites for ovarian cancer diagnosis.","authors":"Deepa Bisht, Sameer Gupta, Amrita Chaurasia, Manisha Sachan","doi":"10.1002/1878-0261.70277","DOIUrl":"10.1002/1878-0261.70277","url":null,"abstract":"<p><p>Ovarian cancer is a heterogeneous gynaecological malignancy characterised by high mortality and an absence of reliable biomarkers for detection. In this study, a CpG-specific, ARMS-PCR approach was employed to evaluate the methylation status of six diagnostically relevant CpG sites in 65 epithelial ovarian cancer tissues and 35 healthy controls. Based on methylation frequency, the top three CpG sites were selected and evaluated in two diagnostic panels. A TaqMan-based MethyLight assay incorporating cg02957270, cg00480298 and Col2A1 (as endogenous control) was developed for tissue and serum cell-free DNA cohort analysis. ARMS-PCR demonstrated diagnostic sensitivities of 80%, 73.3% and 82.3% for singleplex and multiplex panels, respectively. However, the multiplex MethyLight assay achieved 86% sensitivity and 90% specificity, with an AUC of 0.97 in the serum cohort. Furthermore, while ARMS-PCR panels displayed limited clinicopathological correlations, MethyLight showed significant correlations (P < 0.05). Overall, this pilot study highlights the promise of liquid biopsy-based diagnostics using independent hypermethylated and hypomethylated CpG biomarkers for ovarian cancer detection.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2280-2295"},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258858","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":"Spatial and single-nuclei transcriptomics reveals idiosyncratic and generic patterns in papillary and anaplastic thyroid cancers.","authors":"Adrien Tourneur, Joel Rodrigues Vitória, Manuel Saiselet, Ligia Craciun, Denis Larsimont, Anne Lefort, Frédérick Libert, Carine Maenhaut, Sabine Costagliola, Maxime Tarabichi, Mirian Romitti, Vincent Detours","doi":"10.1002/1878-0261.70289","DOIUrl":"10.1002/1878-0261.70289","url":null,"abstract":"<p><p>Sixty percent of papillary thyroid cancers (PTCs) are driven by BRAF^V600E, a mutation associated with high inter- and intra-tumoral heterogeneity. PTCs may become highly aggressive anaplastic thyroid cancers (ATCs). While single-cell transcriptomics may resolve this heterogeneity, it is potentially confounded by technical effects whose correction may dampen inter-tumor variations. Here we profiled ATCs and BRAF^V600E PTCs with single-nuclei RNA-seq and spatial transcriptomics, and an experimental design disentangling biological and technical variations. It reveals that much transcriptional variation in cancer cells and several immune cell types is idiosyncratic, that is, tumor-specific, a phenomenon obscured by batch integration in a number of single-cell studies. Idiosyncrasies are associated in some cases with genomic aberrations and global tissue states like hypoxia. Beyond idiosyncrasies, differentiation markers SLC5A5 (NIS), TPO, TG, and TSHR are lost in a sequence mirrored by their gain during human thyroid organoids maturation, suggesting a new classification of cancer cell states. PTC cells retain TSHR expression and show features of partial epithelial-mesenchymal transition (EMT) with a massive expression of FN1, which promotes proliferation via an autocrine loop. In contrast, ATCs undergo full-scale EMT, with expression of mesenchymal extracellular components and loss of TSHR. Finally, we show that the microenvironment of cancer cells is driven by inflammation. These findings may help future stratifications of BRAF^V600E PTCs.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706887","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":"Somatostatin receptor 4 (SSTR4) is a tumor suppressor in cutaneous and head & neck squamous cell carcinomas.","authors":"Ali Taqvi, Tuan Khang Huynh, Adway Kadam, Zahra Kardan, Yue Yan, Amina Jamal Laham, Sampath Kumar Loganathan","doi":"10.1002/1878-0261.70316","DOIUrl":"10.1002/1878-0261.70316","url":null,"abstract":"<p><p>The mutational landscape of head & neck and cutaneous squamous cell carcinomas (HNSCC, cSCC) has major gene alterations involving PIK3CA, NOTCH1, and TP53 among others that contribute to tumorigenesis. In this study, we focused on somatostatin receptor 4 (SSTR4), which was identified in a recent in vivo HNSCC CRISPR screen. Mutations in the SSTR protein family are more commonly implicated in neuroendocrine tumors, and to date, no studies have shown a link between SSTR4 and cSCC/HNSCC. To understand the role of Sstr4 in skin keratinocytes, we employed transcriptomic profiling and proteomic methods and identified enriched pathways and protein-protein interactions (PPIs) networks. Sstr4 activation by J-2156 agonist regulated MAPK-ERK signaling pathway, which simultaneously limited G1 to S phase cell cycle progression. To validate Sstr4 as a driver of cSCC/HNSCC tumorigenesis, we performed a localized and clonal Sstr4 knockout in basal keratinocytes of the Pik3ca^H1047R oncogenic mouse model using ultrasound-guided in-utero lentivirus injection technology. Tumor formation in mice following Sstr4 knockout occurred rapidly around 12 weeks. Our study is the first to uncover Sstr4 role in cSCC/HNSCC through in-vivo models.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689461","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":"Intrapatient tumour heterogeneity and clonal evolution in an autopsy study of metastatic salivary gland cancer.","authors":"Gerben Lassche, Niels J van Ruitenbeek, Charlotte Adang, Luke O'Gorman, Pui Yuen Lee, Willemijn M Klein, Adriana C H van Engen-van Grunsven, Jack A Schalken, Sander Bervoets, Gerald W Verhaegh, Carla M L van Herpen","doi":"10.1002/1878-0261.70315","DOIUrl":"10.1002/1878-0261.70315","url":null,"abstract":"<p><p>Genetic tumour heterogeneity, driven by clonal evolution, contributes to therapy resistance in many cancers. Most salivary gland cancers, including adenoid cystic carcinoma (AdCC) and myoepithelial carcinoma (MECA), lack effective systemic treatments, highlighting the need to characterise their evolutionary profiles. In this autopsy study, we reconstructed genetic heterogeneity and clonal evolution in two patients with metastatic AdCC and one patient with metastatic MECA. Radiology-guided autopsy was performed between 12 and 56 h after out-of-hospital death. One hundred forty-nine tumour samples were snap-frozen, of which 17 (4-7 per patient) were selected for whole-genome sequencing. Phylogenetic reconstruction was performed using CONIPHER. Autopsy revealed multiple metastatic sites not visible on antemortem or postmortem imaging. MYB-NFIB gene fusions were present across all tumour sites from the two AdCC patients, while a LIFR-PLAG1 fusion was detected in all samples from the MECA patient. All three cases showed extensive genetic tumour heterogeneity and branched phylogenies, suggestive of parallel evolution. Histologic growth patterns were consistent across metastatic sites. Overall, this study demonstrated marked genetic heterogeneity and branched evolution in these AdCC and MECA patients.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684726","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":"EDNRB-dependent endothelin signaling reduces proliferation and promotes proneural-to-mesenchymal transition in gliomas.","authors":"Donovan Pineau, Leonor Garcia, Hugo Arnold, Antonija Hanžek, Maialen Arrieta, Laurent R Gauthier, Christine Granotier-Beckers, François D Boussin, Amaury Herbet, Marie Hautière, Valentin Asei-Ceschino, Clémentin Jacques, Laura Brard, Thomas Harnois, Valérie Coronas, Bruno Constantin, Aurélien Chatelier, Jean Chemin, Serge Urbach, Martial Seveno, Szimonetta Hideg, Chantal Ripoll, Kasandra Aguilar-Cázarez, Min Zheng, Guo-Hao Huang, Sheng-Qing Lv, Lei Zhang, Philippe Rondard, Laurent Prezeau, Jean-Philippe Pin, Hugues Duffau, Luc Bauchet, Valérie Rigau, Franck Denat, Charles Truillet, Didier Boquet, Jean-Philippe Hugnot","doi":"10.1002/1878-0261.70223","DOIUrl":"10.1002/1878-0261.70223","url":null,"abstract":"<p><p>Diffuse gliomas are primary brain tumors including glioblastomas (GB), astrocytomas, and oligodendrogliomas, the latter two harboring IDH1 mutations and exhibiting slower progression. Gliomas display cellular plasticity, with transitions between astrocyte-like, oligodendrocyte-like, progenitor-like, and mesenchymal-like states driven by genetic alterations and microenvironmental signals. The proneural-to-mesenchymal transition (PMT), associated with increased malignancy, is tightly regulated by the tumor microenvironment, notably through cytokine signaling and non-tumor cell interactions. Endothelins (ET-1, ET-2, ET-3), vasoactive peptides mainly produced by vascular cells, signal through the G-protein-coupled receptors EDNRA and EDNRB and were previously suggested to promote glioma proliferation based on serum-based models. Here, we revisited endothelin signaling using eleven serum-free glioma lines and tumor samples. Multi-omics and electrophysiological analyses identified EDNRB as the predominant receptor, enriched in astrocyte-like cells, increased by BMPs or growth factor withdrawal, and repressed by interferons, IL-6 family cytokines, endothelins, and Hippo/YAP signaling. EDNRA was confined to a perivascular tumor subpopulation and induced by Notch signaling selectively in GB. Functionally, endothelins reduced proliferation while promoting migration and PMT via EDNRB-dependent Ca²⁺ signaling, ERK/STAT3 activation, and apamin-sensitive SK2/SK3 potassium channel activity. Collectively these findings establish endothelin signaling as an important regulator of glioma cell plasticity and behavior.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1933-1962"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776307","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":"DNA methylation and expression of MAPRE3 affect overall survival of early-stage non-small cell lung cancer patients.","authors":"Chao Chen, Jiancheng Cheng, Ruili Hou, Xiaoyuan Zheng, Li Su, Maria Moksnes Bjaanæs, Anna Karlsson, Maria Planck, Johan Staaf, Åslaug Helland, Manel Esteller, David C Christiani, Feng Chen, Xiaofei Cao, Ruyang Zhang","doi":"10.1002/1878-0261.70260","DOIUrl":"10.1002/1878-0261.70260","url":null,"abstract":"<p><p>The MAPRE3 gene is aberrantly expressed in several cancers. We profiled DNA methylation in tumor tissues from early-stage non-small cell lung cancer (NSCLC) patients and assessed associations with overall survival (OS). Significant CpG probes were validated in The Cancer Genome Atlas (TCGA). The methylation level of cg12821679_MAPRE3 showed significant associations with OS in lung squamous cell carcinoma (LUSC) (HR = 0.32, P = 6.55 × 10^-7), but it was not observed in lung adenocarcinoma (LUAD). In LUSC, MAPRE3 expression was significantly correlated with cg12821679_MAPRE3 (r = 0.17, P = 2.96 × 10^-3) and potential trans-regulated genes were enriched in the Nicotine addiction pathway. Additionally, MAPRE3 expression showed significant associations with OS in both LUAD and LUSC (LUAD: HR_{low vs high} = 2.28, P = 2.40 × 10^-3; LUSC: HR_{low vs high} = 1.61, P = 0.0244). The association between smoking cessation and overall survival was significantly modified by MAPRE3 expression (HR_interaction = 0.69, P = 0.0282). Smoking cessation improved OS only in patients with high MAPRE3 expression (HR = 0.56, P = 2.82 × 10^-3). We conclude MAPRE3 may predict NSCLC prognosis and influence the prognostic benefit of smoking cessation.</p>","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2008-2022"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776342","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}