Abstract
BackgroundMicrosatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC). However, this conclusion is controversial. In addition, MSs can be a useful marker for loss of heterozygosity (LOH) of genes, but this finding has not been well studied. Here, we aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRC.MethodsWe detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel by STR scanning and cloning/sequencing. We further analyzed the relationship between MSI/LOH status and clinical features or outcomes by Pearson’s Chi-square test, Fisher’s exact test and the Kaplan–Meier method.ResultsThe findings indicated that the MSI rates of B5 loci were all higher than those of loci in tumor-related genes. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcomes, while MSI/LOH of the B5 panel failed to predict outcomes in CRC. MSI of BAT25, MSI/LOH of BAT26 and MSI of the B5 panel showed closer relationships with mucinous carcinoma. In addition, LOH-H of the B5 panel was associated with increased lymphatic metastasis.ConclusionsIn summary, MSI/LOH of certain loci or the whole panel of B5 is related to clinical features, and several loci within tumor-related genes showed prognostic value in the outcomes of CRC.
Highlights
Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC)
MS in tumor‐related genes Using SSRHunter software, we identified 145 microsatellite loci in 19 genes that are closely related to CRC tumorigenesis, including 4 mismatch repair (MMR) genes (MLH1, MSH6, PMS2 and MSH2), 7 tumor suppressor (TS) genes (TP53, CDKN1A, ATM, APC, MCC, BBC3, and PTEN), 7 oncogenes (KRAS, NUP88, BRAF, LIMS1, MDM2, MYC and TMEM97), and 1 DNA repair (DNAR) (MGMT)
MSI/loss of heterozygosity (LOH) status in tumor‐related genes Based on previous findings in CRC, we first selected 19 genes that are closely related to CRC tumorigenesis
Summary
Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC) A few studies have indicated that different LOH mutation frequencies of loci might be related to the biological behavior of CRC [14, 15]. MSI/LOH mutations of the loci or panels recommended for the B5 panel and tumor-related genes correlated with the clinical features of CRC and could be used for determining treatments of individual patients. The development of novel robust biomarkers for the CRC population may be beneficial for the prognosis and prediction of chemotherapeutic responses
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