Upregulation of HOXA13 as a potential tumorigenesis and progression promoter of LUSC based on qRT-PCR and bioinformatics.

In this study, we investigated the levels of homeobox A13 (HOXA13) and the mechanisms underlying the co-expressed genes of HOXA13 in lung squamous cancer (LUSC), the signaling pathways in which the co-expressed genes of HOXA13 are involved and their functional roles in LUSC. The clinical significance of 23 paired LUSC tissues and adjacent non-tumor tissues were gathered. HOXA13 levels in LUSC were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HOXA13 levels in LUSC from The Cancer Genome Atlas (TCGA) and Oncomine were analyzed. We performed receiver operator characteristic (ROC) curves of various clinicopathological features of LUSC. Co-expressed of HOXA13 were collected from MEM, cBioPortal and GEPIA. The functions and pathways of the most reliable overlapped genes were achieved from the Gene Otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The protein-protein interaction (PPI) networks were mapped using STRING. HOXA13 in LUSC were markedly upregulated compared with those in the non-cancerous controls as demonstrated by qRT-PCR (LUSC: 0.330±0.360; CONTROLS: 0.155±0.142; P =0.021). TCGA (LUSC: 6.388±2.097, CONTROLS: 1.157±0.719; P <0.001) and Hou's study from Oncomine (LUSC: 1.154±0.260; CONTROLS: 0.957±0.065; P =0.001) showed the same tendency. Meanwhile, the area under the curve (AUC) of TNM was calculated as 0.877 with P =0.002. Based on the HOXA13 expression data from TCGA, the ROC of the tissue types was calculated as AUC=0.971 ( P <0.001). In addition, 506 genes were filtered as co-expression genes of HOXA13. The 3 most significant KEGG pathways were metabolic pathways ( P =5.41E-15), the calcium signaling pathway ( P =3.01E-11), and the cAMP signaling pathway ( P =5.63E-11). MAPK1, GNG7, GNG12, PRKCA were selected as the hub genes. In conclusion, HOXA13 was upregulated and related to the TNM stage in LUSC. The expression of hub genes in LUSC might be deregulated by HOXA13. Moreover, the 4 co-expressed hub genes of HOXA13 might be crucial biomarkers for the diagnosis and prognosis of LUSC, as well as the development of novel therapeutic targets against LUSC.
Competing Interests: None.
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