Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3284-3298
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3284
Canopy FGF signaling regulator 3 affects prognosis, immune infiltration, and PI3K/AKT pathway in colon adenocarcinoma
Xu-Can Gao, Biao-Huan Zhou, Zhou-Xin Ji, Qiang Li, Hui-Ning Liu
Xu-Can Gao, Biao-Huan Zhou, Zhou-Xin Ji, Qiang Li, Hui-Ning Liu, Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong Province, China
Author contributions: Gao XC, Zhou BH, Ji ZX, Li Q, and Liu HN designed the research study; Gao XC, Zhou BH, and Ji ZX performed the research; Li Q and Liu HN analyzed the data; Gao XC and Zhou BH wrote the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: The clinical sample collection process was performed after the approval of the local Ethics Committee. The study was reviewed and approved by the Shenzhen People’s Hospital Institutional Review Board (No. LL-KY-2021816).
Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.
Data sharing statement: No additional data are available.
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: Xu-Can Gao, MD, Doctor, Department of Anorectal Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), No. 1017 Dongmen North Road, Cuizhu Street, Luohu District, Shenzhen 518020, Guangdong Province, China.logia@szhospital.com
Received: March 23, 2024
Revised: May 14, 2024
Accepted: June 4, 2024
Published online: July 15, 2024
Processing time: 111 Days and 8.6 Hours
Abstract
BACKGROUND

Colon adenocarcinoma (COAD) is a malignant tumor of the digestive system. The mechanisms underlying COAD development and progression are still largely unknown.

AIM

To identify the role of canopy FGF signaling regulator 3 (CNPY3) in the development and progression of COAD by using bioinformatic tools and functional experiments.

METHODS

Bioinformatic data were downloaded from public databases. The associations of clinicopathological features, survival, and immune function with the expression of CNPY3 were analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis were used to explore the related pathways. Then, quantitative real-time PCR and immunohistochemistry were used for validation of CNPY3 expression in clinical samples and tumor cell lines. Cell lines with CNPY3 knockdown were constructed to further analyze gene functions. The functional experiments included proliferation, invasion, migration and apoptosis assays.

RESULTS

In both the TCGA cohort and the merged dataset, elevated CNPY3 expression was observed in tumor tissues. High CNPY3 expression correlated with adverse survival and compromised immune functions. Functional enrichment analysis suggested that the pro-oncogenic properties of CNPY3 might be linked to the PI3K-AKT signaling pathway. CNPY3 expression was validated at both the RNA and protein levels. Functional assays indicated that cell proliferation, invasion, and migration were inhibited and cell apoptosis was promoted after CNPY3 knockdown. Additionally, Western blot results revealed the downregulation of key proteins in the PI3K/AKT pathway following CNPY3 knockdown. PI3K/AKT pathway activator reversed the decrease in proliferation, invasion, and migration and the increase in apoptosis. Notably, CNPY3 knockdown still affected the cells when the pathway was inhibited.

CONCLUSION

This study showed that CNPY3 is upregulated in COAD and might regulate COAD development and progression by the PI3K/AKT pathway. Thus, CNPY3 might be a promising therapeutic target.

Keywords: Canopy FGF signaling regulator 3, Colon cancer, Biomarker, Immune infiltration, Prognosis

Core Tip: First, this is the first study reporting that canopy FGF signaling regulator 3 (CNPY3) was up-regulated in colon adenocarcinoma and might regulate tumor development and progression. Second, CNPY3 expression was validated in clinical samples and tumor cell lines. Third, functional experiments indicated that cell proliferation, invasion, and migration were inhibited and cell apoptosis was promoted after CNPY3 knockdown.