FAM83A may serve as a potential prognostic indicator for stomach adenocarcinoma

Currently, gastric cancer clinical biomarkers are susceptible to interference, causing low specificity or sensitivity. Some also fail to reflect molecular heterogeneity and predict prognosis individually, so urgent clinical need exists for new biomarkers. FAM83A is a member of the family with sequence similarity 83 (FAM83) family, which could predict the prognosis of lung adenocarcinoma (LUAD). However, the relationship between FAM83A and stomach adenocarcinoma (STAD) prognosis remains unclear. Therefore, this study aims to investigate the expression of FAM83A in STAD and its role in predicting prognosis, with the aim of providing novel potential prognostic biomarkers for clinical practice.

We obtained The Cancer Genome Atlas (TCGA)/Genotype-Tissue Expression (GTEx) of 408 STAD patients via the Gene Expression Profiling Interactive Analysis (GEPIA), collected 70 post-radical resection gastric cancer patient samples from Harbin Medical University Cancer Hospital, and retrieved patient information from the hospital's electronic medical record system. Telephone follow-ups were performed bimonthly until overall survival (OS) endpoint or last follow-up date. Tumor recurrence or metastasis was determined through a combination of imaging examinations (e.g., computed tomography), and the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria were used primarily to evaluate treatment response during follow-up. Additionally, Western blot, immunohistochemistry (IHC), SPSS 25.0 and MedCalc 20.1.0 were used to detect the expression of FAM83A and its clinical significance.

Seventy post-radical gastrectomy STAD patients were enrolled (56 male, 14 female), including 6 well-, 24 moderately-, and 40 poorly-differentiated cases. According to the pathological tumor node metastasis (pTNM) stage, 3, 15, and 52 patients were in stages I, II, and III, respectively. Western blot of tumor tissues and TCGA/GTEx database analysis revealed FAM83A overexpression in STAD. IHC showed 70% (n=49) of samples had high FAM83A expression, while 30% (n=21) had low expression. Moreover, the expression of FAM83A was associated with pTNM stage (P=0.02) and primary tumor (pT) classification (P=0.001). Kaplan-Meier analysis revealed low FAM83A expression was associated with better OS and disease-free survival (DFS). In addition, Cox univariate analysis revealed high FAM83A expression was associated with poorer OS [hazard ratio (HR) =2.082, 95% confidence interval (CI): 1.153-3.761; P=0.02] and DFS (HR =1.814, 95% CI: 1.005-3.276; P=0.048) in STAD patients. Cox multivariate analysis showed that pTNM stage and lymph node metastasis were independent prognostic factors for OS and DFS, respectively. However, FAM83A lost significance for both OS and DFS in multivariate analysis, possibly due to limited sample size or interactions with other covariates.

FAM83A may serve as a potential indicator of STAD prognosis, but its clinical application requires further validation in studies with larger sample sizes and prospective designs. Future studies are needed to validate the prognostic value of FAM83A through signaling pathway mechanism research and independent cohort verification.