Expressional analysis of MLH1 and MSH2 in breast cancer

Malik, Saima Shakil; Masood, Nosheen; Asif, Muhammad; Ahmed, Parvez; Shah, Zafar Ullah; Khan, Jahangir Sarwar

doi:10.1016/j.currproblcancer.2018.08.001

Cited by 27 publications

(22 citation statements)

References 24 publications

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“…Li et al found that 53BP1 affects breast cancer patients' sensitivity to 5-Fu, it will results poor prognosis 22 . MLH1, XRCC4, 53BP1, ERCC1 and XPA in breast cancer related studies, XRCC4 may be associated with breast cancer risk and the age at which breast cancer is diagnosed 23 , 53BP1 might be a crucial regulator of breast cancer migration and invasion 24 , women who can detect ERCC1 and XPA are at higher risk of breast cancer 25 , MLH1 and MSH2 loss may lead to advanced breast cancer 26 . XRCC1 overexpression can inhibit breast cancer cell proliferation and metastasis 27 .…”

Section: -Fluorouracilmentioning

confidence: 99%

The diagnostic value of DNA repair gene in breast cancer metastasis

Yang

Hao

et al. 2020

Sci Rep

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Breast cancer is the most common malignant tumor in China and even in the world. DNA repair genes can lead to tumor metastasis by affecting cancer cell resistance. Studies have preliminarily shown that DNA repair genes are related to breast cancer metastasis, but it is not clear whether they can be used as a prediction of the risk of breast cancer metastasis. Therefore, this study mainly discusses the predictive value of DNA repair genes in postoperative metastasis of breast cancer. The nested case–control method was used in patients with breast cancer metastasis after surgery (n = 103) and patients without metastasis after surgery (n = 103). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. In protein expression, PARP1 (OR 1.147, 95% CI 1.067 ~ 1.233, P < 0.05), XRCC4 (OR 1.088, 95% CI 1.015 ~ 1.166, P < 0.05), XRCC1 (OR 1.114, 95% CI 1.021 ~ 1.215, P < 0.05), ERCC1 (OR 1.068, 95% CI 1.000 ~ 1.141, P < 0.10) were risk factors for postoperative metastasis of breast cancer. In addition, we used the ROC curve to study the optimal critical values of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA combined with the Youden index, and the effects of MSH2, MLH1, PARP1, XRCC1, XRCC4, 53BP1, ERCC1 and XPA on breast cancer metastasis were verified again. Among them, the risk of metastasis in the PARP1 high expression group was 3.286 times that of the low expression group (OR 3.286, 95% CI 2.013 ~ 5.364, P < 0.05). The risk of metastasis in the XRCC4 high expression group was 1.779 times that of the low expression group (OR 1.779, 95% CI 1.071 ~ 2.954, P < 0.05). The risk of metastasis in patients with ERCC1 high expression group was 2.012 times that of the low expression group (OR 2.012, 95% CI 1.056 ~ 3.836, P < 0.05). So we can conclude that protein expression of PARP1 (cut-off value = 6, Se = 76.70%, Sp = 79.61%), XRCC4 (cut-off value = 6, Se = 78.64%0, Se = 79.61%), ERCC1 (cut-off value = 3, Se = 89.32%, Sp = 50.49%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of metastasis will increases. Due to PARP1, XRCC4 and ERCC1 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-XRCC4 = 0.343; rPAPR1-ERCC1 = 0.335; rXRCC4-ERCC1 = 0.388). The combined diagnosis of the PARR1, XRCC4 and ERCC1 have greater predictive value for the risk of metastasis of breast cancer (Se = 94.17%, Sp = 75.73%; OR 11.739, 95% CI 2.858 ~ 40.220, P < 0.05). The postoperative metastasis of breast cancer could be effectively predicted when the immunohistochemical scores met PARP1 (IHC score) > 6, XRCC4 (IHC score) > 6 and ERCC1 (IHC score) > 3. In addition, the combined diagnosis of PARP1, XRCC4 and ERCC1 has great predictive value for the risk of breast cancer metastasis.

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Section: -Fluorouracilmentioning

confidence: 99%

The diagnostic value of DNA repair gene in breast cancer metastasis

Yang

Hao

et al. 2020

Sci Rep

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“…MMR is involved in the process of tumor cell apoptosis due to DNA damage. The expression level of MLH1 and MSH2 was negatively correlated with FLAD1 due to increased mutation status, and could ultimately promote tumor cell metastasis and progression into advanced BRCA stages 23 . Higher expression of miR422A could affect MMR by changing the expression of MLH1, thus inhibiting the regulatory feedback mechanism between MMR and miRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Flavin Adenine Dinucleotide Synthetase 1 Is an Up-regulated Prognostic Marker Correlated With Immune Infiltrates in Breast Cancer

Zhang

Deng

Tang

et al. 2021

Preprint

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Background: Flavin adenine dinucleotide synthetase 1 (FLAD1) is a prognostic biomarker in several cancers. This study aimed to identify its effect on survival and potential mechanism in breast cancer (BRCA).Methods: We used the OncoMine, PrognoScan, and UALCAN databases and Kaplan-Meier Plotter to explore FLAD1 expression and survival prognosis in pan-cancer and BRCA. The LinkedOmics database, Gene Ontology-Biological Process (GO-BP), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used for co-expression analyses. The Tumor Immune Estimation Resource, Sangerbox online tools, and the Gene Expression Profiling Interactive Analysis database analyzed the relationship between FLAD1 and cancer immune infiltrates. Results: FLAD1 expression was higher in tumor tissue than adjacent normal tissue in many cancers. Increased FLAD1 expression was correlated with poor overall, relapse-free, and disease-free survival in BRCA. The KEGG pathway and GO-BP analyses showed that FLAD1 expression was correlated to the tRNA metabolic process and mitochondrial gene expression. The DNA mismatch repair (MMR) and methylation status indicated a potential BRCA metastasis mechanism. Immune infiltration was associated with MMR, improved BRCA prognosis, and was negatively associated with FLAD1 expression. High FLAD1 expression led to the down-regulation of macrophages and monocyte infiltration, which might relate to cancer metastasis.Conclusions: FLAD1 expression is higher in BRCA than in normal tissue. High FLAD1 expression was associated with worse survival and might be associated with MMR pathway and immune infiltrations. These results suggest that FLAD1 could serve as a novel biomarker for prognosis and metastasis in BRCA.

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“…Instead, germline mutations in MMR genes are associated with hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch Syndrome, an autosomal dominant disease. Moreover, mutations in all the MMR genes, MLH1 and MSH2, PMS2 and MSH6 have been found related to breast cancer susceptibility [50,[80][81][82][83][84].…”

Section: Single Base Variations and Mismatched Base Pairs Are Repairementioning

confidence: 99%

Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

Lodovichi

Cervelli

Pellicioli

et al. 2020

IJMS

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Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.

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Expressional analysis of MLH1 and MSH2 in breast cancer

Cited by 27 publications

References 24 publications

The diagnostic value of DNA repair gene in breast cancer metastasis

The diagnostic value of DNA repair gene in breast cancer metastasis

Flavin Adenine Dinucleotide Synthetase 1 Is an Up-regulated Prognostic Marker Correlated With Immune Infiltrates in Breast Cancer

Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

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