Dataset Information

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer.

ABSTRACT: CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues at both mRNA and protein levels. In the in-house cohort, CDCP1 protein expression was related to several clinicopathological parameters, including age, ER status, PR status, molecular type, and survival status. Kaplan-Meier analysis and Cox regression analysis exhibited that CDCP1 was an important prognostic biomarker in BrCa. In addition, enrichment analysis uncovered that CDCP1 was not only involved in multiple oncogenic pathways, but correlated with overexpression of immune checkpoints. Overall, we reported that increased expression of CDCP1 is a favorable prognostic factor in patients with BrCa. In addition, the correlations between CDCP1 and immune checkpoints provide a novel insight into the adjuvant treatment for immune checkpoint blockade via targeting CDCP1.

SUBMITTER: Zhao J

PROVIDER: S-EPMC9452972 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer.

Zhao Jinlu J Mei Jie J Wang Fengxu F Zhao Xinyuan X Ren Yi Y Zhao Xingyu X Li Wang W Gao Erli E

Journal of oncology 20220831

CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues a ...[more]

PMID: 36090897

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Project description:BackgroundCell division cycle-associated protein 2 (CDCA2) is a member of cell cycle-related proteins. CDCA2 plays a role in the regulation of protein phosphatase 1(PP1) γ-dependent DNA damage response (DDR) and H3 phosphorylation. CDCA2 promotes the tumorigenesis and development of several types of cancers by promoting the proliferation of tumor cells. However, the relationship between CDCA2 expression and the clinicopathological characteristics of hepatocellular carcinoma (HCC) is unknown.MethodsGene expression information and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. The expression of CDCA2 and its correlation to clinical characteristics in HCC were analyzed. The expression level of CDCA2 was validated in HCC cell lines. The relationship between CDCA2 expression and the survival of patients with HCC was analyzed by using Kaplan-Meier method. The prognostic value of CDCA2 in HCC was estimated by Cox regression analysis. The expression difference of CDCA2 between HCC and normal tissues and its correlation to survival were verified in independent datasets. Gene set enrichment analysis (GSEA) was used to screen the CDCA2-related signaling pathways.ResultsCell division cycle-associated protein 2 expression was upregulated in HCC tissues (p < 0.001) and increased CDCA2 was correlated to increased T stage, pathologic stage, histologic grade, and alpha-fetoprotein (AFP) level (p < 0.001). In addition, CDCA2 was overexpressed in HCC cell lines HepG2 and LM3. High CDCA2 expression level was associated with poor overall survival [hazard ratio (HR) = 1.69; 95% CI, 1.20-1.40, p = 0.003], disease specific survival (HR = 1.73; 95% CI, 1.11-2.71, p = 0.016), and progress free interval (HR = 1.74; 95% CI, 1.30-2.34, p < 0.001). Overexpression of CDCA2 and its correlation to poor survival in HCC were verified in Gene Expression Omnibus (GEO) datasets and Kaplan-Meier plotter database. Increased CDCA2 expression was associated with upregulation of PD-L1 (Spearman's coefficient = 0.207, p < 0.001), PD-L2 (Spearman coefficient's = 0.118, p < 0.05), and CTLA4 (Spearman's coefficient = 0.355, p < 0.001). GSEA showed that homologous recombination pathway, insulin signaling pathway, mitogen-activated protein kinase (MAPK) pathway, mismatch repair pathway, mechanistic target of rapamycin (mTOR) pathway, Notch pathway, T cell receptor pathway, toll like receptor pathway, and WNT pathway were enriched in CDCA2 high expression phenotype.ConclusionCell division cycle-associated protein 2 may serve as an independent biomarker for poor prognosis in HCC and increased CDCA2 expression was associated with upregulation of immune checkpoints.

Project description:PurposeHepatocellular carcinoma (HCC) is one of the most commonly diagnosed digestive cancers and the fourth leading cause of death worldwide. Long noncoding RNAs (lncRNAs) with key roles in HCC development and progression have emerged and are used in the diagnosis and prognostic prediction of HCC. The lncRNA gradually increased during hepatocarcinogenesis (GIHCG) is a novel lncRNA with aberrant expression in many tumors, but its prognostic value and biological role in HCC have not been fully studied. Thus, the aim of this study was to explore the expression pattern and potential biological role of GIHCG in HCC.Patients and methodsThe expression pattern of GIHCG in HCC was analyzed in our HCC cohort and validated in The Cancer Genome Atlas (TCGA) database. To assess the prognostic value of GIHCG, survival analyses and Cox regression analyses were carried out in two HCC cohorts. Functional enrichment analysis was used to predict the gene sets and pathways related to aberrant GIHCG expression. Furthermore, the relationship between GIHCG expression and immune infiltration in HCC was analyzed.ResultsGIHCG was highly expressed in HCC tissues compared with normal liver tissues. In addition, high GIHCG expression was significantly correlated with inferior clinicopathological characteristics and shorter survival times. High GIHCG expression was an independent prognostic factor for overall survival and disease-free survival in the HCC cohort in our center and in the TCGA-LIHC cohort. Hallmark terms such as "G2M checkpoint", "MYC targets" and "DNA repair" were enriched in the GIHCG high-expression groups. High GIHCG expression negatively correlated with the infiltration of memory CD4+ and CD8+ T cells, natural killer cells, macrophages, dendritic cells, neutrophils and monocytes.ConclusionThe findings of our study indicate that GIHCG is a biomarker that can be used to predict the prognosis of HCC patients and is correlated with immune cell infiltration in HCC.

Dataset Information

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer.

Publications

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer.

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