Mutational separation and clinical outcomes of TP53 and CDH1 in gastric cancer

doi:10.4240/wjgs.v15.i12.2855

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World Journal of Gastrointestinal Surgery

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1948-9366

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

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.

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

Abstract

BACKGROUND

Gastric cancer (GC) is a deadly tumor with the fifth highest occurrence and highest global mortality rates. Owing to its heterogeneity, the underlying mechanism of GC remains unclear, and chemotherapy offers little benefit to individuals.

AIM

To investigate the clinical outcomes of TP53 and CDH1 mutations in GC.

METHODS

In this study, 202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected. A total of 490 genes were identified using target capture. Through t-test and Wilcoxon rank-sum test, somatic mutations, microsatellite instability, and clinical statistics, including overall survival, were detected, compared, and calculated.

RESULTS

The mutation rates of 32 genes, including TP53, SPEN, FAT1, and CDH1 exceeded 10%. TP53 mutations had a slightly lower overall occurrence rate (33%). The TP53 mutation rate was significantly higher in advanced stages (stage III/IV) than that in early stages (stage I/II) (P < 0.05). In contrast, CDH1 mutations were significantly associated with diffuse GC. TP53 is related to poor prognosis of advanced-stage tumors; nevertheless, CDH1 corresponds to a diffuse type of cancer. TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms.

CONCLUSION

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

Keywords: Gastric cancer; TP53 mutation; CDH1 mutation; Clinical outcome; Somatic mutation; Diffuse gastric cancer

Core Tip: Mutational separation of TP53 and CDH1 in gastric cancer (GC) reveals their distinct mechanisms. TP53 mutations are associated with advanced-stage tumors and poor prognoses, whereas CDH1 mutations are associated with diffuse GC. This study highlights the heterogeneity of GC and provides insights into potential targeted therapies based on specific mutation patterns. Understanding the mutational landscape of TP53 and CDH1 can contribute to personalized treatment approaches for patients with GC.