Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3011-3031
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3011
Adipocytes impact on gastric cancer progression: Prognostic insights and molecular features
Jia-Rong Shang, Jin Zhu, Lu Bai, Delida Kulabiek, Xiao-Xue Zhai, Xia Zheng, Jun Qian
Jia-Rong Shang, Jin Zhu, Lu Bai, Delida Kulabiek, Xiao-Xue Zhai, Xia Zheng, Jun Qian, Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China
Co-corresponding authors: Xia Zheng and Jun Qian.
Author contributions: Shang JR, Zhu J, Bai L, Kulabiek D, and Zhai XX collected, analyzed, and interpreted the data; Shang JR and Zhu J designed the research study and drafted the manuscript; Zheng X and Qian J provided guidance and support throughout the research process, assisted in data collection and analysis, and participated in manuscript revision and editing; All authors read and approved the final manuscript. Zheng X and Qian J are designated as co-corresponding authors based on their equal contributions to the conception, design, and execution of the research project, illustrating their shared responsibility in the development and implementation of the study. They collaborated closely in the acquisition, analysis, and interpretation of data, ensuring a comprehensive and rigorous evaluation of the results. Both authors actively participated in drafting and critically revising the manuscript, providing intellectual input, and approving the final version for submission. They jointly supervised the research, overseeing various aspects of the project to guarantee its integrity and accuracy. Their collaborative efforts and equal contributions underscore the significance of designating them as co-corresponding authors.
Supported by National Traditional Chinese Medicine Inheritance and Innovation Platform Construction Project by National Administration of Traditional Chinese Medicine, No. Y2020CX57; Jiangsu Provincial Administration of Traditional Chinese Medicine, No. MS2023014; and Jiangsu Graduate Student Research and Practice Innovation Program, No. SJCX23_0799.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
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: Jun Qian, Doctor, MD, Chief Physician, Doctor, Professor, Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210000, Jiangsu Province, China. jun_qian@njucm.edu.cn
Received: February 17, 2024
Revised: March 17, 2024
Accepted: May 28, 2024
Published online: July 15, 2024
Processing time: 146 Days and 2.4 Hours
Abstract
BACKGROUND

Adipocytes, especially adipocytes within tumor tissue known as cancer-associated adipocytes, have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer (GC). Their influence on tumor progression and patient prognosis has sparked significant interest in recent research. The main objectives of this study were to investigate adipocyte infiltration, assess its correlation with clinical pathological features, develop a prognostic prediction model based on independent prognostic factors, evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC, and identify and validate genes associated with high adipocyte expression, exploring their potential diagnostic and prognostic value.

AIM

To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers, using public databases and clinical data.

METHODS

Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital, survival and regression analyses were conducted to determine the relevant prognostic factors in GC. Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms, followed by differential gene expression analysis, gene ontology, pathway analysis, and Gene Set Enrichment Analysis. Immune cell infiltration was analyzed using the CIBERSORT algorithm.

RESULTS

Tumor adipocyte infiltration correlated with poor prognosis in GC, leading to the development of a highly accurate and discriminative prognostic prediction model. Key genes, ADH1B, SFRP1, PLAC9, and FABP4, were identified as associated with high adipocyte expression in GC. The diagnostic and prognostic potential of these identified genes was validated using independent datasets. Downregulation of immune cells was observed in GC with high adipocyte expression.

CONCLUSION

GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis. The genes ADH1B, SFRP1, PLAC9, and FABP4 have been identified as holding diagnostic and prognostic significance in GC. These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.

Keywords: Gastric cancer, Adipocytes, Obesity, Tumor biomarker, Cancer associated adipocytes

Core Tip: Adipocytes within tumor tissue [cancer-associated adipocytes (CAA)] play a crucial role in gastric cancer (GC) progression and patient prognosis. This study confirmed that increased CAA expression correlated with adverse GC outcomes, independent of pathological features but potentially linked to patient age. A prognostic model based on key factors offered high accuracy for clinical decisions. Genes like ADH1B, SFRP1, PLAC9, and FABP4 showed diagnostic and prognostic promise with high CAA expression. Immune analysis revealed reduced immune cells in high CAA GC, suggesting increased tumor aggressiveness. These findings underscore the significance of adipocytes in GC, offering potential biomarkers for future diagnostics and therapeutics.