Dataset Information

Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

ABSTRACT: Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consisting of 79 samples from GSE17025 and 20 samples from GSE29981. RNA-sequencing, clinical, and survival data on EC were obtained from The Cancer Genome Atlas cohort. Survival analysis revealed that HOXA5 overexpression was associated with poor overall survival in patients with EAEC (p = 0.044, HR = 1.832, 95% CI = 1.006-3.334). Cox regression analysis revealed that HOXA5 was an independent risk factor for poor prognosis in EAEC. The overexpression of HOXA5 was associated with a higher histological grade of EAEC, and it was also associated with TP53 mutation or the high copy number of EC. Our findings suggest the potential of HOXA5 as a novel biomarker for predicting poor survival outcomes in patients with EAEC.

SUBMITTER: Song C

PROVIDER: S-EPMC10573156 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

Song Changho C Kim Kyoung Bo KB Lee Gi Su GS Shin Soyoung S Kim Byoungje B

International journal of molecular sciences 20230929 19

Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consistin ...[more]

PMID: 37834206

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Project description:Mammaglobin B, also referred to as secretoglobin family 2A member 1 (SCGB2A1), has been reported to be highly expressed in uterine corpus endometrial cancer (UCEC) compared with in the normal endometrium. However, the prognostic value of SCGB2A1 in UCEC remains unclear. The Oncomine, The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium databases were used to explore the differential expression of SCGB2A1. Furthermore, data of patients with UCEC were downloaded from TCGA, and logistic regression analysis, survival analysis, univariate and multivariate analyses, and nomogram construction were performed to identify its prognostic value in UCEC. Additionally, gene set enrichment analysis (GSEA) was utilized to estimate the mechanisms of SCGB2A1 in UCEC. Finally, immune infiltration of SCGB2A1 in UCEC was analyzed using the Tumor Immune Estimation Resource. Decreased mRNA and protein expression levels of SCGB2A1 were significantly associated with poor prognostic clinicopathological characteristics (all P<0.05). Additionally, low expression levels of SCGB2A1 were associated with decreased survival of patients with UCEC compared with high expression levels of SCGB2A1. Furthermore, the independent prognostic value of SCGB2A1 in UCEC was identified by univariate and multivariate analyses. A nomogram based on 6 variables, including SCGB2A1 expression, was developed for the estimation of the 1-, 3-, and 5-year survival probability in UCEC. Additionally, GSEA suggested that the vascular endothelial growth factor, PTEN, platelet-derived growth factor, DNA repair, KRAS signaling, and PI3K-AKT-mTOR signaling pathways were differentially enriched in the low SCGB2A1 expression phenotype. Finally, high infiltration levels of CD8+ T cells were associated with SCGB2A1 in UCEC and this was associated with prognosis. The present results indicated that SCGB2A1 may be a promising independent prognostic factor in UCEC. These signaling pathways may be crucial for the regulation of UCEC via SCGB2A1.

Project description:BackgroundLeukemia inhibitory factor (LIF) exhibits significant tumor-promoting function, while its cognate receptor (LIFR) is considered to act as either a tumor promoter or suppressor. Dysregulation of LIF and LIFR is associated with the initiation, progression and metastasis of multiple cancer entities. Although increasing numbers of studies are revealing an indispensable critical role of LIFR in tumorigenesis for various different cancers, no systematic analysis of LIFR has appeared thus far.MethodsHere, we comprehensively analyzed the expression profile and prognostic value of LIFR, and correlations between LIFR and the infiltration of immune cells and clinicopathological parameters across different tumor types using several bioinformatic tools. The expression profile of LIFR in various tumor types and clinical stages was investigated using the TIMER2 and GEPIA2 databases. Genetic alternations of LIFR were extracted from cBioPortal. The prognostic value of LIFR was assessed using GEPIA2 and Sanger box databases, and correlations between LIFR expression and immune infiltration were analyzed using the CIBERSORT method and TIMER2 database. The correlations between LIFR expression and immune and stromal scores were assessed using ESTIMATE. We also analyzed correlations between LIFR and immunoregulators. Finally, we detected an effect of LIFR on Uterine Corpus Endometrial Carcinoma (UCEC) and evaluated the expression level of LIFR in clinical UCEC samples.ResultsAberrant expression of LIFR in cancers and its prognosis ability, especially in UCEC was documented. Significantly lower levels of LIFR expression level correlated with better prognosis in multiple tumor types. LIFR expression was positively correlated with the abundance of cancer-associated fibroblasts (CAFs) and endothelial cells in the tumor microenvironment. Additionally, LIFR expression was strongly associated with the presence of immune modulators and checkpoint genes. Overexpression of LIFR suppressed the migration and invasion of UCEC cells in vitro.ConclusionOur pan-cancer detection data provided a novel understanding of the roles of LIFR in oncogenesis.

Dataset Information

Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

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Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

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