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Overexpression of CXXC5 is a strong poor prognostic factor in ER+ breast cancer.

ABSTRACT: CXXC5 is a newly identified CXXC-type zinc finger family protein, which is encoded by the CXXC5 gene localised to the 5q31.3 chromosomal region. Previous studies revealed that CXXC5 is associated with various malignant tumours. The aim of the present study was to investigate the prognosis prediction of CXXC5 in different breast cancer subtypes via the Gene Expression Omnibus database and bc-GenExMiner. CXXC5 overexpression was observed as associated with a poor prognosis for oestrogen receptor positive (ER+) breast cancer. Basal-like breast cancer and triple-negative breast cancer also suggest a poor prognosis, however their CXXC5 expression was low and could not be used as a prognostic factor. The CXXC5 correlated genes and their enriched Gene Ontology (GO) terms were obtained. Among those enriched GO terms, GO:0070062 (extracellular exosome) had the greatest number of associated genes and the associated genes of GO:0000122 (negative regulation of transcription from RNA polymerase II promoter) and GO:0008134 (transcription factor binding) contained CXXC5. These results suggest that overexpression of CXXC5 is a strongly poor prognostic factor in ER+ breast cancer. However, the role of CXXC5 in breast cancer requires further investigation.

SUBMITTER: Fang L

PROVIDER: S-EPMC6006432 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Overexpression of CXXC5 is a strong poor prognostic factor in ER+ breast cancer.

Fang Lei L Wang Yu Y Gao Yang Y Chen Xuejun X

Oncology letters 20180507 1

CXXC5 is a newly identified CXXC-type zinc finger family protein, which is encoded by the <i>CXXC5</i> gene localised to the 5q31.3 chromosomal region. Previous studies revealed that CXXC5 is associated with various malignant tumours. The aim of the present study was to investigate the prognosis prediction of CXXC5 in different breast cancer subtypes via the Gene Expression Omnibus database and bc-GenExMiner. CXXC5 overexpression was observed as associated with a poor prognosis for oestrogen rec ...[more]

PMID: 29928427

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Project description:BackgroundAccumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear.MethodsThe clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer.ResultsWe found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.ConclusionsThese findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

Dataset Information

Overexpression of CXXC5 is a strong poor prognostic factor in ER+ breast cancer.

Publications

Overexpression of CXXC5 is a strong poor prognostic factor in ER+ breast cancer.

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