Agatsuma Yuya, Shimizu Dai, Umeda Shinichi, Tanaka Haruyoshi, Hattori Norifumi, Hayashi Masamichi, Kanda Mitsuro, Tanaka Chie, Nakayama Goro, Fujiwara Michitaka, Kodera Yasuhiro
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;
Cancer Genomics Proteomics. 2025 Jan-Feb;22(1):55-69. doi: 10.21873/cgp.20487.
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.
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 FAM32A mRNA 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.
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 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.
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.
背景/目的：开发预测癌症患者预后的新生物标志物有望有助于治疗选择，从而改善治疗结果。在本研究中，我们从公共数据库中提取了一个与患者预后相关的候选基因，并研究了该基因在胃癌中的分子和生物学功能及临床意义。
我们分析了癌症基因组图谱数据库，并将序列相似性家族32成员a（FAM32A）鉴定为候选基因。我们分别研究了FAM32A mRNA和蛋白表达在300例和176例胃癌患者中的临床病理意义。我们通过使用小干扰RNA抑制胃癌细胞系中FAM32A的表达来评估其分子和生物学功能。
在聚合酶链反应（PCR）队列中，FAM32A低表达组的疾病特异性生存（DSS）显著缩短[风险比（HR）=1.586；95%置信区间（95%CI）=1.056 - 2.382，p = 0.026]。在免疫组织化学队列中，FAM32A（-）组的总生存期（HR = 1.703；95%CI = 1.050 - 2.764，p = 0.031）和DSS（HR = 2.123；95%CI = 1.185 - 3.804，p = 0.011）显著缩短。多变量Cox风险分析显示，FAM32A（-）是DSS的独立不良预后因素（p < 0.001）。FAM32A敲低的AGS细胞系对5-氟尿嘧啶（5-FU）表现出显著抗性，且在给予5-FU后凋亡减少。基因集富集分析表明，在用5-FU处理的FAM32A敲低的AGS细胞中，与p53信号通路相关的基因表达降低。
FAM32A抑制降低了5-FU诱导的凋亡。FAM32A低表达与胃癌预后不良相关，提示其作为生物标志物的潜力。
