MLH1, MSH2, MRE11, and XRCC1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Donís, Sergio Piñeiro; González, Alba Pérez; Alves, Mônica Ghislaine Oliveira; Carvalho, Bruna F do Carmo; Ferreira, Camila Cristina Panisello; Almeida, Janete Días; Padín-Iruegas, María Elena; Chamorro-Petronacci, Cintia; Peñaranda, José Manuel Suárez; Sayáns, Mario Pérez

doi:10.1097/pai.0000000000000929

Cited by 9 publications

(5 citation statements)

References 31 publications

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“…In multiple gastric cancers (MGC) characterized by the presence of more than two different tumors in the stomach, the MSH2 mutations, particularly germline MSH2 X314 _splice variants, may contribute to carcinogenesis, suggesting the consideration of more radical surgery and/or anti-PD-1/PD-L1 therapy ( Wang et al, 2020 ). In oral diseases, the study supports that patients with MSH2 overexpression may easily present with oral squamous cell carcinoma ( Donís et al, 2021 ). Moreover, MSH2 mutation was found in 31% of patients with Lynch syndrome-associated GBMs, indicating that MSH2 may play important role in the progression of GBM ( Kim et al, 2022 ).…”

Section: Discussionsupporting

confidence: 68%

Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma

et al. 2022

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Glioblastoma (GBM) is the most common brain tumor, with rapid proliferation and fatal invasiveness. Large-scale genetic and epigenetic profiling studies have identified targets among molecular subgroups, yet agents developed against these targets have failed in late clinical development. We obtained the genomic and clinical data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and performed the least absolute shrinkage and selection operator (LASSO) Cox analysis to establish a risk model incorporating 17 genes in the CGGA693 RNA-seq cohort. This risk model was successfully validated using the CGGA325 validation set. Based on Cox regression analysis, this risk model may be an independent indicator of clinical efficacy. We also developed a survival nomogram prediction model that combines the clinical features of OS. To determine the novel classification based on the risk model, we classified the patients into two clusters using ConsensusClusterPlus, and evaluated the tumor immune environment with ESTIMATE and CIBERSORT. We also constructed clinical traits-related and co-expression modules through WGCNA analysis. We identified eight genes (ANKRD20A4, CLOCK, CNTRL, ICA1, LARP4B, RASA2, RPS6, and SET) in the blue module and three genes (MSH2, ZBTB34, and DDX31) in the turquoise module. Based on the public website TCGA, two biomarkers were significantly associated with poorer OS. Finally, through GSCALite, we re-evaluated the prognostic value of the essential biomarkers and verified MSH2 as a hub biomarker.

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Section: Discussionsupporting

confidence: 68%

Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma

et al. 2022

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“…DNA repair genes over-expressed in constant ph -KD tumors include several components previously linked to damage accumulation, cancer formation, and/or poor cancer prognosis ( Table 1 ), like Mms4 ( Dewalt, Kesler et al 2014 ), RecQ4 ( Maire, Yoshimoto et al 2009 , Su, Meador et al 2010 , Xu, Chang et al 2021 ), PolH ( Tomicic, Aasland et al 2014 , Sonobe, Yang et al 2024 ), Tipin/Timeless ( Zhou, Zhang et al 2020 , Chen, Zhang et al 2022 ), Claspin ( Choi, Yang et al 2014 ), MRNIP ( Staples, Barone et al 2016 , Bennett, Wilkie et al 2020 , Wang, Zhao et al 2022 ), FANCI ( Smogorzewska, Matsuoka et al 2007 , Li, Yu et al 2023 ), MMR proteins (Msh2, Mlh1, Msh6) ( Shcherbakova and Kunkel 1999 , Velasco, Albert et al 2002 , Li, Liu et al 2008 , Wagner, Webber et al 2016 , Wilczak, Rashed et al 2017 , Chakraborty, Dinh and Alani 2018 , Donis, Gonzalez et al 2021 , Zhou, Xiao and Chen 2024 ), and Rif1 ( Liu, Mei et al 2018 , Mei, Liu et al 2018 , Sad, Mohamed et al 2021 ). Similarly, genes down regulated in constant ph -KD tumors include known components required for DNA repair and replication fork protection in the presence of replication damage, like the PCNA variant PCNA2 ( Feng, Xia et al 2023 ) ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

Rawal,

Loubiere,

Butova

et al. 2024

Preprint

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Cancer initiation and progression are typically associated with the accumulation of driver mutations and genomic instability. However, recent studies demonstrated that cancers can also be purely initiated by epigenetic alterations, without driver mutations. Specifically, a 24-hours transient down-regulation of polyhomeotic (ph-KD), a core component of the Polycomb complex PRC1, is sufficient to drive epigenetically initiated cancers (EICs) in Drosophila, which are proficient in DNA repair and are characterized by a stable genome. Whether genomic instability eventually occurs when PRC1 down-regulation is performed for extended periods of time remains unclear. Here we show that prolonged depletion of a PRC1 component, which mimics cancer initiating events, results in broad dysregulation of DNA replication and repair genes, along with the accumulation of DNA breaks, defective repair, and widespread genomic instability in the cancer tissue. A broad mis-regulation of H2AK118 ubiquitylation and to a lesser extent of H3K27 trimethylation also occurs, and might contribute to these phenotypes. Together, this study supports a model where DNA repair and replication defects amplify the tumorigenic transformation epigenetically induced by PRC1 loss, resulting in genomic instability and cancer progression.

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“…MSH2 is an essential part of the DNA mismatch repair system for DNA damage repairment [ 23 , 24 ]. According to the previous reports, the expression MSH2 was increased in oral squamous cell carcinoma and decreased in breast and gastric cancer [ 19 , 25 , 26 ]. MSH2 may have a functional consequence in different types of cancer, which is worthy of our further study.…”

Section: Discussionmentioning

confidence: 95%

“…It has been reported that MSH2 expression is increased in low-grade and high-grade urothelial malignancy [ 27 ]. In addition, MSH2 was overexpressed in patients with colon cancer and oral squamous cell carcinoma [ 19 , 28 ]. The research results showed above agreeing with our conclusions.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Expression and Prognostic Value of MSH2 in Pan-Cancer Based on Bioinformatics

Qiu

Ding

Liao

et al. 2021

BioMed Research International

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Background. MutS homolog 2 (MSH2), with the function of identifying mismatches and participating in DNA repair, is the “housekeeping gene” in the mismatch repair (MMR) system. MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. However, the expression and prognostic significance of MSH2 have not been studied from the perspective of pan-cancer. Methods. The GTEx database was used to analyze the expression of MSH2 in normal tissues. The TCGA database was used to analyze the differential expression of MSH2 in pan-cancers. The prognostic value of MSH2 in pan-cancer was assessed using Cox regression and Kaplan-Meier analysis. Spearman correlations were used to measure the relationship between the expression level of MSH2 in pan-cancer and the level of immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Results. MSH2 is highly expressed in most type of cancers and significantly correlated with prognosis. In COAD, KIRC, LIHC, and SKCM, the expression of MSH2 was significantly positively correlated with the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils. In THCA, MSH2 expression correlated with CD8+T Cell showed a significant negative correlation. MSH2 had significantly negative correlations with stromal score and immune score in a variety of cancers and significantly correlated with TMB and MSI of a variety of tumors. Conclusions. MSH2 may play an important role in the occurrence, development, and immune infiltration of cancer. MSH2 can emerge as a potential biomarker for cancer diagnosis and prognosis.

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MLH1, MSH2, MRE11, and XRCC1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma

Abstract: Background: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC).

Cited by 9 publications

References 31 publications

Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma

Comprehensive development and validation of gene signature for predicting survival in patients with glioblastoma

Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

Analysis of the Expression and Prognostic Value of MSH2 in Pan-Cancer Based on Bioinformatics

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