Molecular mechanisms and differences in lynch syndrome developing into colorectal cancer and endometrial cancer based on gene expression, methylation, and mutation analysis

PURPOSE: The aim of this study was to screen biomarkers specific to Lynch syndrome (LS) with colorectal cancer (CRC) or endometrial cancer (EC) to explore the mechanisms by which LS develops into CRC and EC and their differences. METHODS: Differentially expressed or differentially methylated genes and differential mutations were identified in 10 LS, 50 CRC, and 50 EC patients from TCGA, and genes overlapping between LS and CRC or EC (named SGs-LCs and SGs-LEs, respectively) were identified. Afterward, we annotated the enriched GO terms and pathways and constructed a protein–protein interaction (PPI) network. Finally, samples from 10 clinical cases with MSI-H/MSS CRC and EC were collected to verify the mutations and their correlations with five LS pathogenic genes in the SGs-LCs and SGs-LEs. RESULTS: A total of 494 SGs-LCs and 104 SGs-LEs were identified and enriched in 106 and 14 GO terms, respectively. There were great differences in the gene count and enriched terms between SGs-LCs and SGs-LEs. In the PPI network, SST, GCG, SNAP25, and NPY had the highest degree of connection among the SGs-LCs, and KIF20A and NUF2 had the highest degree of connection among the SGs-LE. In the SGs-LCs and SGs-LEs, the genes whose expression levels affected the survival of LS, CRC or EC patients were quite different. CONCLUSIONS: COL11A1 was found to be mutated in MSS CRC patients, similar to the mutations of MSH6. SST, GCG, SNAP25, and NPY may be biomarkers for the development of LS into CRC, and KIF20A and NUF2 may be markers of LS developing into EC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10552-021-01543-w.