Evaluation of the HOXA11 level in patients with lung squamous cancer and insights into potential molecular pathways via bioinformatics analysis

Abstract

BackgroundThis study was carried out to discover the underlying role that HOXA11 plays in lung squamous cancer (LUSC) and uncover the potential corresponding molecular mechanisms and functions of HOXA11-related genes.MethodsTwenty-three clinical paired LUSC and non-LUSC samples were utilized to examine the level of HOXA11 using quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of HOXA11 was systematically analyzed based on 475 LUSC and 18 non-cancerous adjacent tissues from The Cancer Genome Atlas (TCGA) database. A total of 102 LUSC tissues and 121 non-cancerous tissues were available from Oncomine to explore the expressing profiles of HOXA11 in LUSC. A meta-analysis was carried out to further assess the differential expression of HOXA11 in LUSC, including in-house qRT-PCR data, expressing data extracted from TCGA and Oncomine databases. Moreover, the enrichment analysis and potential pathway annotations of HOXA11 in LUSC were accomplished via Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of hub genes and according correlations with HOXA11 were assessed to further explore the biological role of HOXA11 in LUSC.ResultsHOXA11 expression in LUSC had a tendency to be upregulated in comparison to adjacent non-cancerous tissues by qRT-PCR. TCGA data displayed that HOXA11 was remarkably over-expressed in LUSC compared with that in non-LUSC samples, and the area under curves (AUC) was 0.955 (P < 0.001). A total of 1523 co-expressed genes were sifted for further analysis. The most significant term enriched in the KEGG pathway was focal adhesion. Among the six hub genes of HOXA11, including PARVA, ILK, COL4A1, COL4A2, ITGB1, and ITGA5, five (with the exception of COL4A1) were significantly decreased compared with the normal lung tissues. Moreover, the expression of ILK was negatively related to HOXA11 (r = − 0.141, P = 0.002).ConclusionHigh HOXA11 expression may lead to carcinogenesis and the development of LUSC. Furthermore, co-expressed genes might affect the prognosis of LUSC.

An inverse interaction betweenHOXA11andHOXA11-ASis associated with cisplatin resistance in lung adenocarcinoma

“…However, a meta-analysis of data gathered from The Cancer Genome Atlas (TCGA) and Oncomine microarrays of 934 LUAD and 319 normal control tissues (the normal controls included tissues from healthy individuals combined with adjacent tumor samples and only 32 pairs of LUAD tissues and adjacent nontumorous tissues) revealed that HOXA11 is significantly overexpressed in LUAD tissues and that the expression level of HOXA11 is significantly higher in patients with lymphoid metastases and an advanced clinical stage, indicating the potential oncogenic role of HOXA11 in the genesis of LUAD [31]. Similar results have also been reported in lung squamous cell carcinoma (LUSC) by bioinformatics analysis [32]. Thus, the molecular mechanisms of HOXA11 in lung cancer pathogenesis mostly remain elusive and require further investigation.…”

Deciphering The Potential Role of Hox Genes in Pancreatic Cancer

“…We hypothesize that HoxB8 is also a metastasis promoter in pancreatic cancer. Downregulation of HoxA10, HoxA11, and HoxB13 in KPA cells is unexpected, because these Hox genes act as tumor-promoting genes in several types of cancers [59,60,61,62]. There are two possible explanations for this discrepancy.…”

Expression Profile and Prognostic Values of HOXA Family Members in Laryngeal Squamous Cell Cancer

“…Overexpression of HOXA11 has been observed in ovarian cancer (28), bladder cancer (29), renal cell carcinoma (29) and lung cancer (30), while downregulation of HOXA11 has been observed in gastric cancer (31) and glioblastoma (32). In glioblastoma, overexpression of HOXA11 confers a tumor suppressive effect, reduces treatment resistance and contributes to a favorable prognosis (32).…”