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ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications.

ABSTRACT: The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mutation-mediated alterations conferred by the ErBb family on cholangiocarcinoma and other cancers enhances tumor aggressiveness and chemoresistance by contributing to the tumor microenvironment. This review summarizes the recent findings on the molecular functions of the ErBb family and their mutations during the progression of cholangiocarcinoma. It also discusses the developments and applications of various devising strategies for targeting the ErBb family through different inhibitors in various stages of clinical trials, which are essential for improving targeted clinical therapies.

SUBMITTER: Jin W

PROVIDER: S-EPMC7408920 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications.

Jin Wook W

Journal of clinical medicine 20200716 7

The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mut ...[more]

PMID: 32708604

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Project description:BackgroundRecently, many studies have suggested that the aberrant expression of c-erbB-2 existed in oral cancer (OC) patients and had a correlation with poor clinical features across OC patients. Considering the inconsistent results among published articles, we performed the meta-analysis to assess the prognostic and clinical effect of c-erbB-2 expression on oral tumors.MethodsWeb of Science, Embase, and PubMed were retrieved to acquire relevant publications based on selection criteria, up to February 8, 2020. Pooled odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were applied to evaluate the associations between c-erbB-2 expression and overall survival (OS), disease specific survival, disease-free survival as well as clinicopathology of OC.ResultsA total of 30 literatures with 1499 patients for survival of OC were enrolled in this meta-analysis. The results indicated that c-erbB-2 overexpression was significantly associated with poor OS (HR = 2.40, 95% CI = 1.53-2.55, P < .05), disease specific survival (HR = 2.60, 95% CI = 1.11-4.10, P < .05) and disease-free survival (HR = 2.22, 95% CI = 1.46-2.99, P < .05). Subgroup analysis based on race showed that the significant prognostic value of c-erbB-2 in OC was found both in Caucasians and Asians (OS of Caucasians, HR = 2.90, 95% CI = 1.50-4.31, P < .05; OS of Asians, HR = 1.90, 95% CI = 1.27-2.53, P < .05). Moreover, OC patients with enhanced c-erbB-2 expression were prone to male (OR = 1.97, 95% CI = 1.22-3.19, P < .05), advanced TNM stage (OR = 1.84, 95% CI = 1.17-2.88, P < .05), lymph node metastasis (OR = 2.23, 95% CI = 1.47-3.36, P < .05) and advanced grade (OR = 1.98, 95% CI = 1.30-3.01, P < .05), but not associated with distant metastasis (OR = 1.65, 95% CI = 0.98-3.04, P > .05).Conclusionsc-erbB-2 may be a potential indicator in the prediction of prognosis and clinicopathological features in OC patients.

Dataset Information

ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications.

Publications

ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications.

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