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Clinical significance of CCBE1 expression in lung cancer.

ABSTRACT: Lymph node metastasis (LNM) is one of the major causes of cancer?associated morbidity and mortality in patients with lung cancer following radical pulmonary carcinoma resection. The present study aimed to investigate the relationship between the expression of collagen and calcium?binding epidermal growth factor domain?containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of lung cancer. The present study included 40 patients with lung cancer that underwent pulmonary carcinoma resection, including 10 patients with LNM, and 10 control patients who underwent pulmonary bullae resection. CCBE1 and LYVE1 expression was assessed in samples from normal and tumor tissue using polymerase chain reaction, western blot analysis and immunohistochemistry. CCBE1 expression appeared to be decreased in lung tumor tissue and further downregulated in samples from patients with LNM, and was revealed to be correlated with poor clinical outcome. Conversely, LYVE1 expression appeared to be upregulated in lung cancer tissue. In conclusion, the present results suggested that CCBE1 and LYVE1 may have potential as biomarkers for the identification of lung cancer patients at a high risk of LNM.

SUBMITTER: Li P

PROVIDER: S-EPMC5783450 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Clinical significance of CCBE1 expression in lung cancer.

Li Peng P Cong Zhuangzhuang Z Qiang Yong Y Xiong Lei L Tang Li L Zhang Yu Y Wu Haiwei H Yi Jun J Jing Hua H Li Demin D Shen Yi Y

Molecular medicine reports 20171129 2

Lymph node metastasis (LNM) is one of the major causes of cancer‑associated morbidity and mortality in patients with lung cancer following radical pulmonary carcinoma resection. The present study aimed to investigate the relationship between the expression of collagen and calcium‑binding epidermal growth factor domain‑containing protein 1 (CCBE1) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) in tumor tissue with the clinical prognosis of lung cancer. The present study included 4 ...[more]

PMID: 29207117

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Project description:OBJECTIVE:Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer (NSCLC) and their clinical significance by observing patient prognosis. METHODS:VEGFR2 and NRP-1 were assessed by immunohistochemistry (IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor (KDR) and NRP-1 copy number gain (CNG) was assessed by fluorescence in situ hybridization (FISH). The distributions of overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test. RESULTS:Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG (+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue (?(2)=11.22, P=0.001; ?(2)=9.82, P=0.001, respectively); similar results were obtained using CNGs (?(2)=4.39, P=0.036; ?(2)=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status (P<0.05), but not age, gender or pathology type (P>0.05). VEGFR2 showed a strong correlation with NRP-1 (Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG (Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression (P<0.05). CONCLUSIONS:According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis (P<0.05 for OS and PFS). This information will be beneficial for clinical anti-angiogenic treatment in NSCLC.

Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

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Clinical significance of CCBE1 expression in lung cancer.

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Clinical significance of CCBE1 expression in lung cancer.

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