Comparative Analysis of Primary Tumour and Matched Metastases in Colorectal Cancer Patients: An Investigation of the Genomic, Proteomic and Post-Transcriptional Regulation Profiles

Abstract

Introduction: Approximately 50% of patients with primary colorectal carcinoma develop liver metastases. This study investigates the possible molecular discrepancies between primary colorectal cancer (pCRC) and their respective metastases. Methods: A total of 22 pairs of pCRC and metastases were tested. Mutation profiling of 26 cancer-associated genes was undertaken in 22/22primary-metastasis tumour pairs using next-generation sequencing, whilst the expression of a panel of six microRNAs (miRNAs) was investigated using qPCR in 21/22 pairs and 22 protein biomarkers was tested using Reverse Phase Protein Array (RPPA) in 20/22 patients’ tumour pairs. Results: Among the primary and metastatic tumours, the mutation rates for the individual genes are as follows: TP53 (86%), APC (44%), KRAS (36%), PIK3CA (9%), SMAD4 (9%), NRAS (9%) and 4% for FBXW7 , BRAF , GNAS and CDH1 . The primary-metastasis tumour mutation status was identical in 54/60 (90%) loci. However, there was discordance in heterogeneity status in 40/58 genetic loci (z-score = 6.246, difference = 0.3793, P < 0.0001). Furthermore, there was loss of concordance in miRNA