Comprehensive clinical implications of homeobox A10 in 3,199 cases of non-small cell lung cancer tissue samples combining qRT-PCR, RNA sequencing and microarray data.

In the current study, we proposed to explore the potential role and related signaling pathways of Homobox A10 (HOXA10) in non-small cell lung cancer (NSCLC). HOXA10 levels in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were detected by qRT-PCR and the expression of HOXA10 was significantly up-regulated in the NSCLC tissue of all 55 pairs (P = 0.037). Overexpression of HOXA10 was closely correlated with the clinical stage of LUSC (P = 0.011). HOXA10 expression in RNA sequencing data based on 1, 077 cases exhibited concordant significant up-regulation in NSCLC, LUAD and LUSC (P < 0.001). In NSCLC, HOXA10 expression was closely correlated to patient T stage (P = 0.006). In LUAD, HOXA10 expression was compactly correlated to patient N stage (P = 0.02). Some of the microarrays from Gene Expression Omnibus (GEO) and ArrayExpress showed consistent over-expression of HOXA10 levels in NSCLCs. More importantly, the combined SMD value was 0.052 (95% CI: 0.29-0.75, P < 0.001) generated by meta-analysis from 47 datasets based on 4, 616 cases of NSCLC. The area under the curve (AUC) of SROC supported the over-expression of HOXA10 in NSCLC as being 0.88 (95% CI: 0.81-0.93), with sensitivity and specificity of 0.88 (95% CI: 0.81-0.93) and 0.56 (95% CI: 0.44-0.66), respectively. In addition, 111 co-expressed genes were collected from cBioPortal and enriched in "cell cycle", "cell adhesion molecules", "p53 signaling", and "adherens junction". Interestingly, an up-regulation trend of HOXA10 protein expression was also observed in NSCLC through tissue chips and immunohistochemistry. In conclusion, the overexpression of HOXA10 may play a pivotal role in the tumorigenesis of NSCLC, and this effect is observed more obviously in LUSC than in LUAD.