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

Abstract

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.

Identification of Prognostic Immune-Related Genes by Integrating mRNA Expression and Methylation in Lung Adenocarcinoma

“…DNA methylation represents the most common molecular mechanism of epigenetic modification when genes undergo changes such as cell proliferation or differentiation, alternative splicing, and genetic imprinting [ 43 – 45 ]. Studies have shown that DNA methylation can be closely related to the development of different tumors, thus making methylated genes potential biomarkers for the diagnosis and prognosis of lung cancer [ 24 , 46 – 48 ]. A previous study has indicated that the expression level of S100A16 might be modulated by its DNA hypomethylation and serves as an independent prognostic indicator of unfavorable OS and RFS in LUAD [ 48 ].…”

“…Studies have shown that DNA methylation can be closely related to the development of different tumors, thus making methylated genes potential biomarkers for the diagnosis and prognosis of lung cancer [ 24 , 46 – 48 ]. A previous study has indicated that the expression level of S100A16 might be modulated by its DNA hypomethylation and serves as an independent prognostic indicator of unfavorable OS and RFS in LUAD [ 48 ]. There are studies of methylation levels in other genes that demonstrate the effect of methylation on the prognosis of LUAD.…”

High KRT8 Expression Independently Predicts Poor Prognosis for Lung Adenocarcinoma Patients

“…For instance, Zhou et al have found that epithelial cell transforming 2 ( ECT2 ) expression is increased in LUAD and may predict poor OS and RFS for LUAD patients, but not for LUSC patients [31]. Using the UCSC Xena browser to analyze the same TCGA-LUAD dataset [32], Chen et al and Yu et al have demonstrated that high expression of lactate dehydrogenase-A ( LDHA ) [33] and the S100 protein family member S100A16 [34] might be independent prognostic markers of inferior OS for LUAD patients.…”

Integrin Subunit beta 8 (ITGB8) Upregulation Is an Independent Predictor of Unfavorable Survival of High-Grade Serous Ovarian Carcinoma Patients

“…Statistical analysis was conducted as recommended in previous studies [23–25]. In brief, GraphPad Prism 6.0 (GraphPad Inc., La Jolla, CA, USA) and SPSS 19.0 software package (SPSS Inc., Chicago, IL, USA) were used for data integration and analysis.…”