Basic Study
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World J Gastrointest Surg. Dec 27, 2023; 15(12): 2855-2865
Published online Dec 27, 2023. doi: 10.4240/wjgs.v15.i12.2855
Mutational separation and clinical outcomes of TP53 and CDH1 in gastric cancer
He-Li Liu, Huan Peng, Chang-Hao Huang, Hai-Yan Zhou, Jie Ge
He-Li Liu, Jie Ge, Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Huan Peng, Clinical Nursing Teaching and Research Section, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Chang-Hao Huang, Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Hai-Yan Zhou, Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Co-first authors: He-Li Liu and Huan Peng.
Author contributions: Liu HL, Peng H, and Ge J designed the study; Huang CH collected and analyzed the clinical data; and Zhou HY wrote the paper; Liu HL and Peng H contributed equally to this work as co-first authors. The reasons for designating Liu HL and Peng H as co-first authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-first authors accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resulting paper. This also ensures the effective communication and management of post-submission matters, ultimately enhancing the quality and reliability of the paper. Second, the research team encompasses authors with a variety of expertise and skills from different fields, and the designation of co-first authors best reflects this diversity. This also promotes a more comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Liu HL and Peng H contributed efforts of equal substance throughout the research process. The choice of these researchers as co-first authors acknowledges and respects their equal contribution, while recognizing the spirit of teamwork and collaboration in this study. In summary, we believe that designating Liu HL and Peng H as co-first authors fits our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity. All authors approved the final version of the article.
Supported by Guangdong Yiyang Healthcare Charity Foundation, No. JZ2022014.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Xiangya Hospital, Central South University (NO. 2023087).
Conflict-of-interest statement: No potential conflicts of interest were disclosed by authors.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jie Ge, MD, Attending Doctor, Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Kaifu District, Changsha 410008, Hunan Province, China. gejie@csu.edu.cn
Received: September 13, 2023
Peer-review started: September 13, 2023
First decision: September 28, 2023
Revised: October 18, 2023
Accepted: November 21, 2023
Article in press: November 21, 2023
Published online: December 27, 2023
Processing time: 105 Days and 3.9 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is the third most common malignant tumor in China, and its incidence is much higher than that in Western countries. This study provides crucial molecular data on GC in Chinese patients because large-scale Chinese genetic evidence is lacking. This study revealed that TP53 and CDH1 mutations affect two important pathways in the occurrence and development of GC. The pathogenesis of GC in the Han Chinese population (in the middle and lower reaches of the Yangtze River), as well as the diagnosis and treatment of GC, would benefit from our findings.

Research motivation

One of the challenges to the design of effective treatments for GC is heterogeneity, its poses an obstacle for the uniform therapy plan irrespective of specific subtypes of tumors in clinical practice.

Research objectives

TP53 and CDH1 have been reported to be closely related to GC; therefore, we aimed to investigate the clinical outcomes of TP53 and CDH1 mutations in GC.

Research methods

Two hundred and two primary GC tissues and matched non-cancerous (NC) tissues were sampled via surgery. After DNA extraction for cancer tissue and NC tissue, DNA was captured using customized panel from Roche NimbleGen Inc. The customized panel included the exons and hotspots of 490 genes with a total length of 1 Mb 10 sequencer (Illumina, Inc).

Research results

The mutation rates of 32 genes exceeded 10% including TP53, SPEN, FAT1, and CDH1 etc. We found that TP53 mutations had a slightly lower overall occurrence rate (33%), whereas the mutation type was similar to that reported in other studies. The TP53 mutation rate was significantly higher in the advanced stages (stage III/IV) than that in the early stages (stage I/II) (P < 0.05). In contrast, we also found that CDH1 mutation is significantly related to diffuse GC. TP53 is related to the poor prognosis of advanced-stage tumors; nevertheless, CDH1 corresponds to a diffuse type of cancer. Moreover, TP53 was exclusively mutated to CDH1, which is the major reason for the two different GC mechanisms.

Research conclusions

Different somatic mutation patterns of TP53 and CDH1 indicate two major mechanisms underlying GC.

Research perspectives

Understanding the mutational landscape of TP53 and CDH1 would positively affect the pathogenesis of GC in the Han Chinese population (in the middle and lower reaches of the Yangtze River), as well as guiding the diagnosis and treatment of GC.