Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2021; 13(12): 2101-2113
Published online Dec 15, 2021. doi: 10.4251/wjgo.v13.i12.2101
MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos
Loraine Kay D Cabral, Cynthia A Mapua, Filipinas F Natividad, Caecilia H C Sukowati, Edgardo R Cortez, Ma Luisa D Enriquez
Loraine Kay D Cabral, Cynthia A Mapua, Filipinas F Natividad, Ma Luisa D Enriquez, Research and Biotechnology Group, St. Luke's Medical Center, Quezon City 1112, Philippines
Loraine Kay D Cabral, Caecilia H C Sukowati, Centro Studi Fegato, Fondazione Italiana Fegato ONLUS, Trieste 34149, Italy
Edgardo R Cortez, Department of Surgery, St. Luke's Medical Center, Quezon City 1112, Philippines
Ma Luisa D Enriquez, Center for Natural Science and Environmental Research, De La Salle University, Manila 1004, Philippines
Author contributions: Enriquez MLD conceptualized the project; Cabral LKD designed and optimized the experiments; Mapua CA screened data of the colorectal cancer databank and performed statistical analysis; Cabral LKD and Sukowati CHC analyzed data and wrote the manuscript; Cortez ER and Natividad FF coordinated specimen collection and funds allocation as study group head and division head respectively; all authors read and approved the manuscript.
Supported by Department of Science and Technology and the Philippine Council for Health Research and Development (DOST-PCHRD) (to Cabral LKD); St. Luke’s Medical Center, Manila, Philippines; and Regione Autonomo FVG in Progetti Internazionali 2021 to the FIF, No. DGR 189 dd 12/2/21.
Institutional review board statement: The clinical study protocol and the revised clinical study protocol (Ref. No. 06-015) had been approved by the St. Luke's Medical Center Institutional Ethics Review Board.
Conflict-of-interest statement: All authors declared that they have no conflicts of interest.
Data sharing statement: The authors may share the data for justified reason.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Loraine Kay D Cabral, BSc, MSc, Research Associate, Research and Biotechnology Group, St. Luke's Medical Center, 279 E Rodriguez Sr. Avenue, Quezon City 1112, Philippines. kay.cabral@fegato.it
Received: May 11, 2021
Peer-review started: May 11, 2021
First decision: June 12, 2021
Revised: June 24, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: December 15, 2021
Processing time: 217 Days and 14.1 Hours
ARTICLE HIGHLIGHTS
Research background

A distinct molecular signature marks a particular subset of sporadic colorectal cancer (CRC). It involves the mismatch repair (MMR) genes silencing due to DNA methylation, leading to microsatellite instability (MSI).

Research motivation

To improve the management of the CRC patients based on their distinct molecular subtypes.

Research objectives

To examine the association of mutL homolog 1 (hMLH1) methylation (MMR gene) and the MSI phenotype in relation to cancer characteristics and patient survival among Filipino sporadic CRC patients.

Research methods

Paired tissues (normal and tumor) from sporadic CRC patients was screened for hMLH1 methylation using methylation specific polymerase chain reaction. Subsequent MSI typing was done by high resolution melting analysis.

Research results

The results of this study showed that hMLH1 methylation was mostly noticed in proximal tumors. Low overall survival was observed in methylated hMLH1 and MSI tumors.

Research conclusions

The epigenetic silencing of hMLH1 as well as MSI may present a distinct pattern of CRC in Filipino patients.

Research perspectives

This is an initial attempt to characterize sporadic CRC in Filipino population. It may shed light in understanding molecular epigenetic modification in CRC as well as its role in tumor development and management.