Aberrant S100A16 expression might be an independent prognostic indicator of unfavorable survival in non-small cell lung adenocarcinoma

S100A16 is a conserved member of the S100 protein family in mammals. Its upregulation was observed in many tumors and is related to malignant transformation. In this study, we explored the independent prognostic value of S100A16 in terms of overall survival (OS) and recurrence-free survival (RFS) by performing a retrospective study, using data in The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD). Besides, by using deep sequencing data in TCGA-LUAD, we also explored the association between S100A16 expression and its DNA methylation and copy number alterations (CNAs). Results showed that the primary LUAD tissues (N = 514) had significantly elevated S100A16 expression compared with the normal lung tissues (N = 59). Based on OS data of 502 primary LUAD cases, we found that high S100A16 expression was correlated with inferior OS. The following univariate and multivariate analysis confirmed that increased S100A16 expression was an independent prognostic indicator of unfavorable OS (HR: 1.197, 95%CI: 1.050–1.364, p = 0.007) and RFS (HR: 1.206, 95%CI: 1.045–1.393, p = 0.011). By examining the DNA methylation data in TCGA-LUAD, we found that some S100A16 DNA CpG sites were generally hypermethylated in normal tissues, but not in LUAD tissues. Regression analysis identified a moderately negative correlation between S100A16 expression and its DNA methylation. In comparison, although DNA amplification (+1/+2) was frequent (378/511, 74%) in LUAD patients, it was not associated with increased S100A16 expression. Based on findings above, we infer that aberrant S100A16 expression might be modulated by its DNA hypomethylation and serves as an independent prognostic indicator of unfavorable OS and RFS in LUAD.