FAM32A Suppression Decreases 5-Fluorouracil-induced Apoptosis and Is Associated With Poor Prognosis in Gastric Cancer

Q: What is the main research question of this study?

The study examines whether FAM32A is associated with gastric cancer prognosis and whether its suppression affects 5-fluorouracil-induced apoptosis and chemoresistance.

Q: How was FAM32A identified as a candidate gene?

A public database approach was used, analyzing The Cancer Genome Atlas and identifying FAM32A (family with sequence similarity 32 member a) as a candidate gene linked to prognosis.

Q: What did the results show about low FAM32A expression?

Low FAM32A expression was associated with significantly shorter disease-specific survival and overall survival, and FAM32A suppression reduced 5-fluorouracil-induced apoptosis.

Sep 23, 2026

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Development of reliable biomarkers to predict cancer prognosis can improve treatment selection and outcomes. This study used public databases to identify FAM32A as a candidate gene linked to patient prognosis in gastric cancer. Clinicopathological analyses evaluated FAM32A mRNA and protein expression in 300 and 176 patients. Functional experiments suppressed FAM32A in gastric cancer cell lines with small interfering RNA to assess molecular effects and chemotherapy response. Results showed low FAM32A expression correlated with worse survival and with reduced 5-fluorouracil-induced apoptosis, indicating potential as a biomarker and prognostic marker.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background/Aim

Materials and Methods

Results

Conclusion

Key Words

Introduction and Rationale

Need for Prognostic Biomarkers

Role of 5-Fluorouracil in Gastric Cancer

Rationale for FAM32A

CANCER GENOMICS & PROTEOMICS 22: 55-69 (2025) doi:10.21873/cgp.20487 FAM32A Suppression Decreases 5-Fluorouracil-induced Apoptosis and Is Associated With Poor Prognosis in Gastric Cancer YUYA AGATSUMA 1 , DAI SHIMIZU 1 , SHINICHI UMEDA 1 , HARUYOSHI TANAKA 1 , NORIFUMI HATTORI 1 , MASAMICHI HAYASHI 1 , MITSURO KANDA 1 , CHIE TANAKA 1 , GORO NAKAYAMA 1 , MICHITAKA FUJIWARA 1,2 and YASUHIRO KODERA 1 1Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; 2Medical xR Center, Nagoya University Hospital, Nagoya, Japan Abstract. Background/Aim: The development of new biomarkers to predict cancer patient prognosis is expected to aid in treatment selection, contributing to improved outcomes . In this study, we extracted a candidate gene associated with patient prognosis from a public database and investigated the molecular and biological functions and clinical significance of the gene in gastric cancer. Materials and Methods: We analyzed The Cancer Genome Atlas database and identified the family with sequence similarity 32 member a (FAM32A) as a candidate gene. We investigated the clinicopathological significance of FAM32AmRNA and protein expression in 300 and 176 gastric cancer patients respectively. We evaluated the molecular and biological functions by suppressing FAM32A expression in gastric cancer cell lines using small interfering RNA. Results: In the polymerase chain reaction (PCR) cohort, low FAM32A expression group showed significantly shorter disease-specific survival (DSS) [hazard ratio (HR)=1.586; 95% confidence interval (95% CI)=1.056-2.382, p=0.026] . In the immunohistochemistry cohort, the FAM32A(–) group had significantly shorter overall survival (HR=1.703; 95% CI=1.050-2.764, p=0.031) and DSS (HR=2.123; 95% CI=1.185-3.804, p=0.011) . Multivariate Cox hazard analysis Correspondence to: Dai Shimizu, Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine 65 Tsurumaicho, Showa-ku, Nagoya 466-8550, Japan. Tel: +81 527442250, Fax: +81 52744225, e-mail: [d-shimizu@med.nagoya-u.ac.jp](d-shimizu@med.nagoya-u.ac.jp) Key Words: Gastric cancer, FAM32A, biomarker, apoptosis, chemoresistance. ©2025 The Author(s) . Published by the International Institute of Anticancer Research. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license ([https://creativecommons.org/licenses/by-nc-nd/4.0](https://creativecommons.org/licenses/by-nc-nd/4.0)). revealed that FAM32A(–) was an independent adverse prognostic factor for DSS (p<0.001) . AGS cell lines with FAM32A knockdown exhibited significant resistance to 5-fluorouracil (5-FU) and reduced apoptosis upon 5-FU administration. Gene set enrichment analysis indicated decreased gene expression related to the p53 signaling pathway in AGS cells with FAM32A knockdown that were treated with 5-FU. Conclusion: FAM32A suppression decreases 5-FU-induced apoptosis. Low FAM32A expression is associated with a poor prognosis in gastric cancer, suggesting its potential as a biomarker. Gastric cancer is the fourth most common cancer worldwide and the second highest cause of cancer-related mortality. The incidence of gastric cancer is particularly high in regions such as East Asia and Eastern Europe (1) . In Japan, between 2001 and 2013, the 5-year survival rate for gastric cancer was 70.6%(2) . The 5-year survival rate for stage I cancer was 83.2%-89.6%, but the 5-year survival rate for stage IV was markedly worse at 14.0% . Gastric cancer often recurs frequently even after radical resection, and the prognosis for recurrent cases is poor. Therefore, identifying biomarkers that sensitively reflect patient prognosis is crucial. Although classical tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), are widely used, their accuracy in stratifying patient prognosis an

FAQs

What is the main research question of this study?

The study examines whether FAM32A is associated with gastric cancer prognosis and whether its suppression affects 5-fluorouracil-induced apoptosis and chemoresistance.

How was FAM32A identified as a candidate gene?

A public database approach was used, analyzing The Cancer Genome Atlas and identifying FAM32A (family with sequence similarity 32 member a) as a candidate gene linked to prognosis.

What did the results show about low FAM32A expression?

Low FAM32A expression was associated with significantly shorter disease-specific survival and overall survival, and FAM32A suppression reduced 5-fluorouracil-induced apoptosis.

Sep 23, 2026

Uploaded by Jiven