Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 24, 2022; 13(10): 779-788
Published online Oct 24, 2022. doi: 10.5306/wjco.v13.i10.779
Somatic mutations in FAT cadherin family members constitute an underrecognized subtype of colorectal adenocarcinoma with unique clinicopathologic features
Liang-Li Wang, Wei Zheng, Xiu-Li Liu, Feng Yin
Liang-Li Wang, Feng Yin, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO 65212, United States
Wei Zheng, Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, United States
Xiu-Li Liu, Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, United States
Author contributions: Wang LL, Zheng W, Liu XL and Yin F collected and analyzed the data, made the tables and figures, and wrote and finalized the manuscript; and all authors have approved the final manuscript.
Institutional review board statement: This study is solely based on the publicly available TCGA PanCancer Atlas database. The Institutional Review Board Approval is not applicable.
Informed consent statement: This study is solely based on the publicly available TCGA PanCancer Atlas database. The Informed Consent Statement is not applicable.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng Yin, MD, PhD, Assistant Professor, Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212, United States. fengyin@health.missouri.edu
Received: July 26, 2022
Peer-review started: July 26, 2022
First decision: August 18, 2022
Revised: August 25, 2022
Accepted: September 15, 2022
Article in press: September 15, 2022
Published online: October 24, 2022
Processing time: 85 Days and 7.8 Hours
Abstract
BACKGROUND

The FAT cadherin family members (FAT1, FAT2, FAT3 and FAT4) are conserved tumor suppressors that are recurrently mutated in several types of human cancers, including colorectal carcinoma (CRC).

AIM

To characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members.

METHODS

We analyzed 526 CRC cases from The Cancer Genome Atlas PanCancer Atlas dataset. CRC samples were subclassified into 2 groups based on the presence or absence of somatic mutations in FAT1, FAT2, FAT3 and FAT4. Individual clinicopathological data were collected after digital slide review. Statistical analysis was performed using t tests and chi-square tests.

RESULTS

This CRC study cohort had frequent mutations in the FAT1 (10.5%), FAT2 (11.2%), FAT3 (15.4%) and FAT4 (23.4%) genes. Two hundred CRC patients (38.0%) harbored somatic mutations in one or more of the FAT family genes and were grouped into the FAT mutated CRC subtype. The FAT-mutated CRC subtype was more commonly located on the right side of the colon (51.0%) than in the rest of the cohort (30.1%, P < 0.001). It showed favorable clinicopathologic features, including a lower rate of positive lymph nodes (pN1-2: 33.5% vs 46.4%, P = 0.005), a lower rate of metastasis to another site or organ (pM1: 7.5% vs 16.3%, P = 0.006), and a trend toward an early tumor stage (pT1-2: 25.0% vs 18.7%, P = 0.093). FAT somatic mutations were significantly enriched in microsatellite instability CRC (28.0% vs 2.1%, P < 0.001). However, FAT somatic mutations in microsatellite stable CRC demonstrated similar clinicopathologic behaviors, as well as a trend of a better disease-free survival rate (hazard ratio = 0.539; 95% confidence interval: 0.301-0.967; log-rank P = 0.073).

CONCLUSION

FAT cadherin family genes are frequently mutated in CRC, and their mutation profile defines a subtype of CRC with favorable clinicopathologic characteristics.

Keywords: FAT cadherin family genes; Colorectal adenocarcinoma; Clinicopathologic features; Prognosis; The Cancer Genome Atlas

Core Tip: Colorectal carcinoma (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. In this study, we aimed to characterize the clinicopathologic features of CRC patients with somatic mutations in FAT cadherin family members. CRC cases have frequent mutations in FAT family genes. The FAT-mutated CRC subtype is more commonly located on the right side of the colon and shows favorable clinicopathologic features, including a lower rate of positive lymph nodes and a lower rate of metastasis to another site or organ, suggesting that the FAT somatic mutation is a potentially independent prognostic factor in CRC.