Investigating genomic, proteomic, and post-transcriptional regulation profiles in colorectal cancer: a comparative study between primary tumors and associated metastases

Hersh Ham-Karim; Ola Negm; Narmeen Ahmad; Mohammad Ilyas

doi:10.1186/s12935-023-03020-7

Investigating genomic, proteomic, and post-transcriptional regulation profiles in colorectal cancer: a comparative study between primary tumors and associated metastases

Cancer Cell Int. 2023 Sep 5;23(1):192. doi: 10.1186/s12935-023-03020-7.

Authors

Hersh Ham-Karim¹, Ola Negm², Narmeen Ahmad³, Mohammad Ilyas^{4

5}

Affiliations

¹ Department of Pharmacy, College of Medicine, Komar University of Science and Technology, Chaq-Chaq-Qualaraisi, Sulaimani, Iraq. Hersh.abdul@komar.edu.iq.
² Division of Medical Sciences and Graduate Entry Medicine, Faculty of Medicine and Health Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
³ Kurdistan Institution for Strategic Studies and Scientific Research, Qirga, Sulaimani, KRG, Iraq.
⁴ Department of Pharmacy, College of Medicine, Komar University of Science and Technology, Chaq-Chaq-Qualaraisi, Sulaimani, Iraq.
⁵ Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK.

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 qPCRin 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 expression status between primary and metastatic tumours, and 57.14-80.95% of the primary-metastases tumour pairs showed altered primary-metastasis relative expression in all the miRNAs tested. Moreover, 16 of 20 (80%) tumour pairs showed alteration in at least 3 of 6 (50%) of the protein biomarker pathways analysed.

Conclusion: The molecular alterations of primary colorectal tumours differ significantly from those of their matched metastases. These differences have profound implications for patients' prognoses and response to therapy.

Keywords: Gene mutations; NGS; Primary tumour and corresponding metastasis; Protein; RPPA; miRNA.