Expression of mismatch repair protein and its significance in breast cancer

GAO Li-xiang; LIU Li; CHEN Ying; LIU Li-min; MA Qiang; SUN Nai-ying; YANG Xing-jie

doi:10.3969/j.issn.1007-8096.2023.08.013

Abstract：Objective To explore the expression of mismatch repair protein in breast cancer by using the technology of bioinformatic analysis combined with experimental verification.Methods From January 2017 to December 2021,136 cases of invasive breast cancer in Sunshine Union Hospital and 40 cases of normal tissues adjacent to breast cancer were collected.The expression of MLH1,PMS2,MSH2 and MSH6 was verified by immunohistochemistry,and the difference between MMRP deletion and normal tissues and the correlation with clinical pathological parameters were analyzed.RNAseq data in level 3 HTSeq-FPKM format were downloaded in BRCA(breast cancer)Project of the Cancer Genome Atlas(TCGA, data in fragments per kilobase per million format was converted into transcripts per million reads format and log2 conversion was performed,Wilcoxon rank sum test was used to compare the expression of MLH1,PMS2,MSH2 and MSH6 between normal controls and cancer tissues,and"ggplot2"package(version 3.3.3)was used to draw the figures.Results Immunohistochemical result confirmed that no MMRP deletion was found in MLH1,PMS2,MSH2 and MSH6 in the adjacent normal group.In the breast cancer group,only one case of triple negative invasive ductal carcinoma was found to have MSH2 deletion,which was judged to be defective mismatch repair(dMMR),and no MMRP deletion was found in other breast cancer groups.The difference of MMRP deletion between breast cancer tissues and adjacent tissues was not statistically significant(P=1.000).There was no statistical significance between MMRP deletion and tumor location,age,tumor size,histological classification and lymph node metastasis.Analysis of TCGA data showed that the deletion rate of MLH1,MSH2 and MSH6 in breast cancer was significantly higher than that in normal tissues(P＜0.0001),and there was no significant difference between the deletion rate of PMS2 and normal tissues(P=0.505).Conclusion Through experimental verification,the difference of PMS2 deletion rate between breast cancer tissues and normal tissues adjacent to cancer is consistent with the result of bioinformatic analysis,while the deletion rates of MLH1,MSH2 and MSH6 in breast cancer are not consistent with the result,the mechanism of which needs further study.