Molecular Carcinogenesis最新文献

{"title":"Targeting TROP2 and Exploiting AUNIP as a Determinant of ADC Cytotoxicity and Chemosensitivity in HNSCC and ESCA Cancers.","authors":"Jiaqi Bai, Feifei Ji, Xiyu Zhao, Haoran Wang, Xiaofeng Huang, Jiahui Wei, Zishu Yang, Siming Chen, Wenxin Zhang, Peijie Zhang, Xiaoyu He, Liangfa Liu, Guotai Xu","doi":"10.1002/mc.70115","DOIUrl":"https://doi.org/10.1002/mc.70115","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) and esophageal carcinoma (ESCA) are anatomically contiguous, frequently co-occurring malignancies that collectively account for substantial global cancer mortality. With half of patients progressing to recurrent or metastatic disease, alternative therapeutic strategies are urgently needed. Antibody-drug conjugates (ADCs) offer promise, but their clinical impact requires identification of robust target antigens and elucidation of resistance mechanisms. Through single-cell transcriptomic analysis followed by experimental validation, we identified TROP2 as a consistently and highly overexpressed cell-surface antigen in HNSCC and ESCA. DS-1062a, a TROP2-directed ADC delivering the camptothecin (CPT)-like topoisomerase I inhibitor deruxtecan (Dxd), demonstrated marked tumor regression in HNSCC and ESCA xenografts. This pronounced sensitivity may be attributable to prevalent homologous recombination deficiency (HRD) in these cancers, conferring vulnerability to DNA single-strand break (SSB)-inducing agents such as PARP inhibitors. However, therapeutic potential is constrained by an incomplete understanding of the regulators of drug sensitivity. To systematically dissect genetic modifiers of SSB-induced cytotoxicity, we performed a genome-wide CRISPR/Cas9 sgRNA knockout screen and identified AUNIP as a determinant of chemosensitivity. AUNIP loss profoundly enhanced DS-1062a cytotoxicity and multiple SSB-inducing chemotherapies across diverse HNSCC and ESCA models. Mechanistically, AUNIP deficiency led to impaired DNA repair, attenuated stress response signaling, and heightened apoptotic susceptibility. These findings establish TROP2 as a therapeutically actionable target and reveal AUNIP as a genetic rheostat governing ADC and chemotherapy response. Co-targeting AUNIP represents a promising strategy to potentiate SSB-inducing therapies and improve outcomes in patients with squamous carcinomas of the upper aerodigestive tract.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840535","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":"Comprehensive Multi-Omics Profiling of Tertiary Lymphoid Structures Reveals Immunogenetic Landscapes and Prognostic Subtypes in Lung Adenocarcinoma.","authors":"Yajie Zhou, Zijian Hu, Lei Xie, Wenxiong Zhang, Haiwei Rao","doi":"10.1002/mc.70120","DOIUrl":"https://doi.org/10.1002/mc.70120","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLSs) are key components of the tumor immune microenvironment and show prognostic relevance in many cancers. However, their genetic association with lung adenocarcinoma (LUAD) is still lacking. This study aims to construct a TLS-related prognostic model through an integrated multi-omics strategy and to elucidate relevant immunogenetic mechanisms. TLS-related genes (TRGs) showing genetically supported associations with LUAD were identified using Mendelian randomization (MR). A TRG-based model was established using machine learning (ML), with its accuracy assessed through a nomogram. Downstream analyses were performed, including immune microenvironment, tumor mutational burden (TMB), pathway enrichment, drug sensitivity profiling, and single-cell RNA sequencing (scRNA-seq). The expression of TRGs was confirmed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The prognostic model we built using the best algorithm showed strong prognostic value (1-, 3-, and 5-year AUCs > 0.75). Individuals classified in the high-risk (H-R) cohort exhibited markedly poorer outcomes (p < 0.001). Incorporation of the risk model into the nomogram improved its predictive accuracy compared with the model without this variable (AUC = 0.769 for risk score). TMB analysis suggested a higher TMB in the H-R group, which may predict a worse prognosis. Drugs targeting the PI3K-AKT-mTOR and cell cycle pathways showed higher efficacy in the H-R group. According to enrichment results, TRGs were mainly involved in immune activation and cell cycle regulation, suggesting that these genes may regulate LUAD prognosis through PI3K-AKT-mTOR and cell cycle pathways. The scRNA-seq analysis showed that the 10 TRGs were predominantly localized within T/NK and myeloid cell clusters, indicating their potential involvement in modulating local immune responses. The differential expression patterns of these genes across multiple cell lines were validated using RT-qPCR. In summary, this comprehensive model highlights the significance of TRGs in LUAD, providing a new paradigm for immunogenetic risk evaluation and personalized therapy.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817902","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":"The Endocrine Disrupting Compounds Bisphenol-A and α-Zeranol Mimic the Estrogen Transcriptional Program to Promote Proliferation and Stemness in Breast Cancer Cells.","authors":"Cassandra Winz, Eric Li, Caroline Xie, Kyo Chang Lee, Kevin Boguszewski, Shlok Rohatagi, Rita Hahn, Ray Rancourt, Philip Furmanski, Nanjoo Suh","doi":"10.1002/mc.70127","DOIUrl":"https://doi.org/10.1002/mc.70127","url":null,"abstract":"<p><p>Excessive activation of the estrogen receptor (ER) drives proliferation, progression, and the formation of breast cancer stem cells (CSCs) in ER-positive breast cancer. Estrogenic endocrine disrupting compounds (EDCs) found in plastics, water, and food are also able to bind to the ER. Thus, we hypothesized that estrogenic EDCs mimic estrogen (E2) in the pathogenesis of breast cancer by promoting their survival and proliferation. Three estrogenic EDCs routinely found in human biosamples were selected for analysis: bisphenol-A (BPA), diethyl-hexyl phthalate (DEHP), and alpha-zeranol (αZAL). We assessed proliferation, transcriptional reprogramming, and CSC formation in breast cancer cell lines. E2, BPA, and αZAL significantly increased cell proliferation in ER-positive, but not ER-negative cell lines. This was reversed after administration of the ER-antagonist, ICI 182,780. BPA and αZAL upregulated estrogen target genes (PGR, TFF1) and increased levels of cell-cycle protein. RNA sequencing analysis revealed that BPA and αZAL altered expression of genes related to cell division, DNA repair, and estrogen signaling, with a substantial transcriptional overlap between EDCs and estrogen treatments. Additionally, BPA and αZAL increased the proportion of CSCs, defined as the CD24^low/CD44^high expressing subpopulation. Overall, these data indicate that BPA and αZAL act as functional estrogen mimics in breast cancer cells, activating canonical estrogen signaling pathways and promoting stem-like characteristics. Notably, this study provides the first transcriptomic and stem-associated characterization of αZAL in ER-positive breast cancer cells, revealing a robust estrogenic mode of action. This work provides mechanistic insight into how environmental EDCs may influence ER-positive breast cancer biology.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817838","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":"EXPRESSION OF CONCERN: Involvement of VILIP-1 (Visinin-Like Protein) and Opposite Roles of Cyclic AMP and GMP Signaling in In Vitro Cell Migration of Murine Skin Squamous Cell Carcinoma.","authors":"","doi":"10.1002/mc.70100","DOIUrl":"10.1002/mc.70100","url":null,"abstract":"","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"642"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355908","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":"NAT10 Modulates Breast Cancer Progression Via Ac⁴C-Mediated Regulation of TRAF6 Expression and Glycolytic Metabolism.","authors":"Weiwei Bai, Meidi Zhu, Xiaochun Kan, Ye Zhang, Yingchun Zhang","doi":"10.1002/mc.70094","DOIUrl":"10.1002/mc.70094","url":null,"abstract":"<p><p>NAT10, an essential enzyme catalyzing RNA ac⁴C modification, is recognized as a critical regulator of tumorigenesis and progression. This study investigates the role and underlying molecular mechanisms of NAT10 in breast cancer. We found that NAT10 is significantly overexpressed in breast cancer tissues compared to adjacent normal tissues, exhibiting high diagnostic accuracy (AUC = 0.9702, p < 0.001). Consistently, NAT10 expression was also elevated in breast cancer cell lines. Knockdown of NAT10 potently inhibited cell viability, glycolysis (as indicated by reduced glucose uptake, lactate production, and ECAR), and metastatic potential (manifested as suppressed migration and invasion) in breast cancer cells. Mechanistically, NAT10 regulated TRAF6 expression and stability through ac⁴C modification; NAT10 knockdown led to reduced ac⁴C enrichment on TRAF6 mRNA and accelerated its degradation. Rescue experiments confirmed that TRAF6 overexpression partially reversed the inhibitory effects of NAT10 knockdown on glycolysis and metastasis. In vivo, NAT10 knockdown significantly suppressed tumor growth in nude mice, which was associated with reduced expression of Ki67 and TRAF6 in tumor tissues. Collectively, our findings highlight NAT10 as a key regulator of breast cancer progression via ac⁴C-mediated TRAF6 modulation, suggesting it as a promising therapeutic target for breast cancer therapy.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"565-576"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271473","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":"TGFβ-Mediated Overexpression of Podoplanin Serves as a Potential Diagnostic Biomarker in Acute Promyelocytic Leukemia.","authors":"Akash Maity, Rohit Kumar, Madhavi Dutta, Ansit Mishra, Jitendra Gawde, Jagruti Patil, Darshana Kadam, Sumeet Mirgh, Anant Gokarn, Hasmukh Jain, Lingaraj Nayak, Bhausaheb Bagal, Sachin Punatar, Manju Sengar, Navin Khattry, P G Subramanian, Prashant Tembhare, Syed K Hasan","doi":"10.1002/mc.70096","DOIUrl":"10.1002/mc.70096","url":null,"abstract":"<p><p>Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide. Although APL is diagnosed using microscopy, immunophenotyping, and FISH/PCR for PML-RARA, morphological overlap with acute myeloid leukemia (AML) -M5 and AML-M2 complicates identification. In resource-limited settings, unavailability of real time -quantitiative PCR (RQ-PCR) or delays in FISH/qualitative RT-PCR results increase the risk of missed or late diagnosis with fatal outcomes. Podoplanin (PDPN), a glycoprotein overexpressed in APL cells, interacts with platelets to mediate thrombosis. We evaluated PDPN expression, regulation, and diagnostic potential in APL. PDPN mRNA (RQ-PCR) and surface protein (flow cytometry) were significantly higher in APL than non-APL AML (p < 0.0001), consistent with TCGA-LAML and BEATAML1.0 datasets. Sensitivity and specificity were 80.7% and 71.43% by RQ-PCR, and 92.86% and 100% by flow cytometry, respectively. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) and TGF- β1 stimulation confirmed SMAD binding and PDPN upregulation. Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"556-564"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181187","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":"Analysis of the Matrix Metalloproteinases Family Profile in Gastric Cancer Suggests Key Matrix Metalloproteinases for Tumor Development and Their Clinical Impact.","authors":"Aline Costa Bastos, André Salim Khayat, Emanuele Raimunda Louzada Moraes, Ágatha Tereza Miranda Tavares, Ronald Matheus da Silva Mourão, Fabiano Cordeiro Moreira, Samir Mansour Moraes Casseb, Samia Demachki, Geraldo Ishak, Williams Fernandes Barra, Rommel Mario Rodríguez Burbano, Paulo Pimentel de Assumpção","doi":"10.1002/mc.70097","DOIUrl":"10.1002/mc.70097","url":null,"abstract":"<p><p>Gastric cancer (GC) is the fifth most common type worldwide, representing a public health problem. Among the genes related to this tumorigenesis, the family of matrix metalloproteinases (MMPs), essential regulators of the extracellular matrix (ECM), stand out for their involvement in the development and progression of GC. Therefore, we aimed to evaluate MMP gene expression variation, its relationship with clinicopathological factors and its transcriptome-wide associations. To this end, RNAseq, correlation network, and biological pathway enrichment analyses were performed on tumor samples from GC and peritumoral samples from patients treated at a reference center in the Northern region of Brazil. Among the 22 investigated MMPs, seven genes (MMP2, MMP3, MMP10, MMP12, MMP14, MMP15, and MMP16) were upregulated in cancer, while MMP8 was downregulated. Increased expression of seven of the eight differentially expressed MMPs was found in early stages of the disease compared to Tumor, Node, Metastasis (TNM) stage IV. MMP16 showed higher expression in the diffuse-type gastric adenocarcinoma. An increased expression of MMP10 was observed in the EBV/TCGA group. A significant reduction in survival was noticed in those patients with lower expression of MMP8, MMP12, and MMP14. Transcriptomic correlation analyses demonstrated that differentially expressed MMPs interact with genes likely involved in cell adhesion, ECM organization, and immune response, such as COL1A2, CDH11, KIRREL1, PPP1R14D, CEACAM8, ZNF423, and PRRX1. The enrichment of biological pathways suggests involvement in processes such as ECM organization, collagen and proteoglycan degradation, suggesting that these genes possibly are involved in carcinogenic dynamics, supporting the role of MMPs in tumor ECM reorganization.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"577-588"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271529","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":"Distinct Tumor Infiltrating Immune Cell Profiles in Mice by Non-Steroidal Anti-Inflammatory Drugs (Aspirin and Naproxen) During TMPRSS2-ERG (Fusion)-Driven and Non-Fusion Driven Prostate Cancer.","authors":"Munendra Singh Tomar, Komal Raina, Neha Mishra, Rama Kant, Jennifer T Fox, Chapla Agarwal, Rajesh Agarwal","doi":"10.1002/mc.70099","DOIUrl":"10.1002/mc.70099","url":null,"abstract":"<p><p>Our previous preclinical studies demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and naproxen significantly inhibited prostate tumorigenesis in a TMPRSS2-ERG fusion-driven model compared to non-fusion models. Since TMPRSS2-ERG fusion-positive tumors display heightened inflammatory signaling and substantial immune infiltration, we hypothesized that the differential efficacy of NSAIDs may arise from their ability to remodel the tumor immune microenvironment. Accordingly, in the present study, we systematically profiled innate and adaptive immune-cell populations: F4/80⁺ macrophages, mast cells, neutrophils, CD3⁺ T cells, CD8⁺ cytotoxic T cells, FoxP3⁺ regulatory T cells, CD20⁺ B cells, IgKC⁺ plasma cells, and Granzyme B⁺ effector cells in highly infiltrated dorso-lateral prostate regions of TMPRSS2-ERG fusion-driven and non-fusion PCa models, with and without NSAID intervention. Our analyses revealed pronounced macrophage infiltration in TMPRSS2-ERG. Pten^flox/flox and Hi-Myc^+/ ^- model, which was further augmented by NSAIDs. Importantly, NSAID intervention shifted macrophage polarization toward an M1-like, pro-inflammatory state, contrasting with the M2-dominant phenotype characteristic of untreated tumors. NSAID treatment reduced mast cell density within the stromal compartment, suggesting suppression of mast cell-mediated tumor-promoting signals. In the fusion model, infiltration of total T cells and CD8⁺ cytotoxic T cells decreased following NSAID exposure, whereas FoxP3⁺ Tregs remained largely unaffected. Both models showed increased B-cell infiltration independent of NSAID efficacy, and no clear correlation was observed between plasma-cell presence and treatment response. Collectively, our findings offer new insight into NSAID-mediated immunomodulation in TMPRSS2-ERG fusion-driven PCa; however, further in-depth immune subtyping and spatial mapping could fully delineate the immunological mechanisms driving NSAID responsiveness.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"589-602"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271481","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":"RETRACTION: Overexpression of 5-lipoxygenase and Its Relation With Cell Proliferation and Angiogenesis in 7,12-Dimethylbenz(α)anthracene-Induced Rat Mammary Carcinogenesis.","authors":"","doi":"10.1002/mc.70098","DOIUrl":"10.1002/mc.70098","url":null,"abstract":"<p><strong>Retraction: </strong>M. Chatterjee, S. Das, K. Roy, and M. Chatterjee, \"Overexpression of 5-lipoxygenase and Its Relation With Cell Proliferation and Angiogenesis in 7,12-Dimethylbenz(α)anthracene-Induced Rat Mammary Carcinogenesis,\" Molecular Carcinogenesis 52, no. 5 (2013): 359-369. https://doi.org/10.1002/mc.21858. The above article, published online on 28 December 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by Wiley Periodicals LLC. A third party reported that portions of the image in Figure 2B had been duplicated and manipulated from another article by some of the same authors [Chatterjee et al. 2011 (https://doi.org/10.1016/j.ejphar.2011.06.039)]. Additionally, the third party reported that the beta-actin band in Figure 3A had been duplicated from an alpha-tubulin band presented in Chatterjee et al. 2011. Further investigation by the publisher found that Figure 5B had been duplicated from another article by different authors [von Euler et al. 2004 (https://doi.org/10.1016/j.bioelechem.2003.10.008)] and also found evidence of additional image manipulation in Figures 3A and 3C. The authors responded to an inquiry by the publisher. However, the authors were unable to provide original, unmodified data or images for the experiments reported in the article and were unable to provide a sufficient explanation for the findings of the investigation. The retraction has been agreed to because evidence of image duplication and manipulation fundamentally compromises the reported conclusions. The authors disagree with the retraction.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"643"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284511","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":"Evaluation of Epidermal Growth Factor Receptor and Its Inducible Feedback Inhibitor Leucine Rich Repeats and Immunoglobulin Like Domains 1 as Prognostic Marker in Oral Cancer.","authors":"Deepika Verma, S S Chauhan, Joginder Kumar, Mohit Arora, Qulsum Akhtar, Lokesh Kadian, Prerna Jain, Vivek Nayyar, Ajoy Roychaudhury, Deepika Mishra, Alok Thakar, Riyaz A Mir","doi":"10.1002/mc.70103","DOIUrl":"10.1002/mc.70103","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a life-threatening disease that ranks sixth amongst the most common human cancers worldwide. In most cases, OSCC development is preceded by oral premalignant disorders (OPMDs). There is an urgent need for more biomarker studies that will aid in early detection, diagnosis, and treatment of OPMD to prevent their transformation to OSCC. Leucine rich repeats and immunoglobulin like domains 1 (LRIG1) are known to negatively regulate EGFR expression. Little is known about the significance of LRIG1 in oral cancer pathogenesis. In a retrospective study, immunohistochemical analysis of EGFR and LRIG1 was carried out in 212 archival oral tissues (100 OSCC, 87 OPMD, and 25 normal), correlated with clinicopathological parameters and disease outcome over 62 months for OSCC patients. Further, gene expression for EGFR and LRIG1 was also evaluated in 160 tissue samples. Significant increase in EGFR in OSCC tissue was observed compared to controls, while LRIG1 levels were found to be downregulated in OSCC and OPMD cases compared to normal tissues (p < 0.05). Kaplan-Meier analysis of patients stratified to high and low LRIG1 expression showed significantly different overall survival (p < 0.05, median survival 1397 and 561 days, respectively). A unique translational impact of our study is that it provides clinical evidence for the potential of LRIG1 downregulation as predictor of poor prognosis in OSCC. These preliminary findings support further research to validate LRIG1 based prognostic tools for oral cancers.</p>","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"630-641"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326685","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}