Molecular Analysis of Prognosis and Immune Infiltration of Ovarian Cancer Based on Homeobox D Genes

Abstract

Background. Homeobox D (HOXD) genes were associated with cancer pathogenesis. However, the role of HOXD genes in ovarian cancer (OC) and the possible mechanisms involved are unclear. In this study, we analyzed the function and regulatory mechanisms and functions of HOXD genes in OC based on comprehensive bioinformatics analysis. Methods. Expression of HOXD1/3/4/8/9/10/11/12/13 mRNA was analyzed between OC tissue and normal tissue using ONCOMINE, GEO, and TCGA databases. The relationship between HOXD expression and clinical stage was studied by GEPIA. The Kaplan-Meier plotter was used to analyze prognosis. cBioPortal was used to analyze the mutation and coexpression of HOXDs. GO and KEGG analyses were performed by the DAVID software to predict the function of HOXD coexpression genes. Immune infiltration analysis was used to evaluate the relationship between the expression of HOXD genes and 24 immune infiltrating cells. Results. The expression of HOXD3/4/8/9/10/11 was significantly lower in OC tissues than in normal ovarian tissues, while the expression of HOXD1/12/13 was significantly higher in OC tissues. The expression of HOXD genes was associated with FIGO stage, primary therapy outcome, tumor status, anatomic neoplasm subdivision, and age. The expression levels of HOXD1/3/4/8/9/10 correlated with tumor stage. HOXD1/8/9 could be served as ideal biomarkers to distinguish OC from normal tissue. Low HOXD9 expression was associated with shorter overall survival (OS) (HR: 0.75; 95% CI: 0.58–0.98; P = 0.034 ) and progression-free survival (PFS) (HR: 0.69; 95% CI: 0.54–0.87; P = 0.002 ). The HOXD coexpression genes were associated with pathways including cell cycle, TGF-beta signaling pathway, cellular senescence, and Hippo signaling pathway. HOXD genes were significantly associated with immune infiltration. Conclusion. The expression of HOXD genes is associated with clinical characteristics. HOXD9 is a new biomarker of prognosis in OC, and HOXD1/4/8/9/10 may be potential therapeutic targets. The members of the HOXD genes may be the response to immunotherapy for OC.

Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma

“…R version 3.6.3 and ggplot2 version 3.3.3 (R Core Team, Vienna, Austria) were used for the statistical analysis and visualization [ 22 , 28 ]. The molecules were hsa-miR-335-5p [MIMAT0000765], and KCNQ1OT1 [ENSG00000269821].…”

“…The molecules were hsa-miR-335-5p [MIMAT0000765], and KCNQ1OT1 [ENSG00000269821]. The data were miRNAseq data from the level 3 BCGSC miRNA Profiling in the TCGA LUAD project and the RNAseq data in the level 3 HTSeq-FPKM format from the TCGA LUAD project [ 9 , 28 ].…”

Expression profile, prognostic values, and immune infiltration of IRX family members in lung adenocarcinoma

“…RNAseq data were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) by Toil process (14). Software was R (version 3.6.3) (statistical analysis and visualization) and R package was mainly ggplot2 [version 3.3.3] (for visualization) were used to analyze the differential expression of IRXs (15).…”

“…The correlation between each two IRXs was assessed using the Pearson correlation coe cient (15,16). Statistical analysis and graphs were done with R software (version 3.6.…”

Homeobox‐D 1 and FTO form a transcriptional–epigenetic feedback loop to promote head and neck cancer proliferation

“…Another study demonstrated that HOXD1 suppresses cell proliferation and cell‐cycle progress in kidney renal clear cell carcinoma (KIRC) based on in silico analysis and functional experiments (Cui et al, 2021a). In addition, HOXD1 was elevated in ovarian cancer tissues and correlated with tumor stage (Chen et al, 2022). Knockdown of HOXD1 could promote breast cancer metastasis (Zheng et al, 2018).…”