Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2024; 16(1): 118-132
Published online Jan 15, 2024. doi: 10.4251/wjgo.v16.i1.118
Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study
Shi-Lin Lv, Pei Guo, Jun-Rong Zou, Ren-Sheng Chen, Ling-Yu Luo, De-Qiang Huang
Shi-Lin Lv, Ling-Yu Luo, De-Qiang Huang, Hospital of Gastroenterology, Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Pei Guo, Department of Pathology, Shenzhen Hospital of Southern Medical University, Shenzhen 518000, Guangdong Province, China
Jun-Rong Zou, Institute of Urology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
Ren-Sheng Chen, Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Huang DQ and Lv SL conceived and designed the study, analyzed and interpreted the data, and wrote the manuscript; Guo P, Zou JR, Luo LY and Chen RS collected clinical samples and completed the related experiments; all authors approved the final manuscript.
Supported by National Nature Science Foundation of China, No. 82060450, No. 82360517, No. 81460374, and No. 31460304; and Nature Science Foundation of Jiangxi Province of China, No. 20232BAB206086, No. 20192BAB205072, No. 20203BBGL73206, No. 2017BCB23086, No. 2017BAB205062, and No. 20181BAB205050.
Institutional review board statement: This study involving patient participants was reviewed and approved by the Ethics Committee of Shanghai Outdo Biotech Company (Shanghai, China) (NO: SHYJS-CP-1801009).
Informed consent statement: Written informed consent was obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: De-Qiang Huang, MD, Hospital of Gastroenterology, Institute of Digestive Diseases, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizen Street, Nanchang 330006, Jiangxi Province, China. hdq0515@ncu.edu.cn
Received: August 4, 2023
Peer-review started: August 4, 2023
First decision: October 23, 2023
Revised: November 20, 2023
Accepted: December 12, 2023
Article in press: December 12, 2023
Published online: January 15, 2024
Processing time: 159 Days and 22.8 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer is a significant health concern and understanding the molecular mechanisms underlying its progression and metastasis is crucial. The TGF-β/SMAD3 and VEGFR-1 signaling pathways have been identified as important players in gastric cancer metastasis, with SMAD3 phospho-isoforms emerging as a critical prognostic marker.

Research motivation

Given the clinical significance of gastric cancer, there is a pressing need to elucidate the prognostic value and interrelationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer. This study aims to address this gap in knowledge.

Research objectives

The primary objective of this study was to determine the prognostic significance and relationship between SMAD3 phospho-isoforms (pSMAD3C(S423/425) and pSMAD3L(S204)) and VEGFR-1 in gastric cancer.

Research methods

This observational single-center study enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues. Immunohistochemical staining and tissue microarrays were utilized to measure the expression levels of TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1. Prognosis and survival information of the patients were recorded, and statistical analyses including Pearson's correlation coefficient, Chi-squared test, and Kaplan-Meier survival analysis were employed.

Research results

The study revealed that TGF-β1 and VEGFR-1 expression were significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. High expression of pSMAD3L(S204) and VEGFR-1 was associated with larger tumors, later N stages, tumor size, and pathological grading, and was correlated with unfavorable overall survival outcomes. Multivariate analysis identified high expression of pSMAD3L(S204) and VEGFR-1 as independent risk factors for the prognosis of GC patients.

Research conclusions

The co-upregulation of pSMAD3L(S204) and VEGFR-1 may serve as a predictive marker for poor gastric cancer prognosis, suggesting a potential role for pSMAD3L(204) in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Research perspectives

Future research could focus on elucidating the underlying molecular mechanisms linking SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer metastasis, potentially paving the way for targeted therapeutic interventions.