Abstract
BackgroundCervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. ClC-3 may be an important promoter for aggressive metastasis of malignant tumors. In this research, we explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis.MethodsParaffin-embedded cervical (n = 168) and lymph node (n = 100) tissue specimens were analysed by immunohistochemistry. Fresh human cervical tissue specimens (n = 165) and four human cervical cell lines were tested for ClC-3 mRNA and protein expression levels by quantitative real-time PCR and western blotting. The relationship between the expression levels of ClC-3, the pathological characteristics of the carcinoma, and the clinical prognosis were statistically analysed.ResultsIn normal and precancerous (LSIL, HSIL) cervical tissues as well as cervical carcinoma tissues, both ClC-3 mRNA and protein expression levels increased significantly (p < 0.05). The expression level of ClC-3 was closely-related to the histological differentiation (p = 0.029), tumour staging (p = 0.016), tumour size (p = 0.039), vascular invasion (p = 0.045), interstitial infiltration depth (p = 0.012), lymphatic metastasis (p = 0.036), and HPV infection (p = 0.022). In an in vitro experiment, ClC-3 mRNA and protein were found to be overexpressed both in the HeLa and SiHa cell lines, but low expression levels were detected in the C-33A and H8 cell lines (p < 0.05). Furthermore, the high expression levels of ClC-3 was significantly correlated to poor survival in cervical carcinoma patients (Log-rank test, p = 0.046).ConclusionsThese data suggest that overexpression of ClC-3 is closely associated with human cervical carcinoma progression and poor prognosis; this suggests that ClC-3 may function as a patent tumour biomarker and a latent therapeutic target for cervical carcinoma patients.
Highlights
Cervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research
We identified the expression level of ClC-3 at the protein level using IHC in paraffin-embedded specimens derived from cervical cancer patients that were either lymph node metastasis positive (LP, n = 50) and lymph node metastasis negative (LN, n = 50)
The present study investigated the relationship between the ClC-3 gene expression levels and its underlying clinical significance in human cervical carcinoma to illustrate its impact in the progression of cervical cancer
Summary
Cervical carcinoma is a major gynecological cancer and causes cancer-related deaths in worldwide, the latent pathogenesis and progress of cervical cancer is still under research. We explore the ClC-3 expression in cervical carcinoma and its underlying clinical significance, trying to illuminate ClC-3 probable function in the neoplasm malignant behavior, development and prognosis. Cervical carcinoma is a major gynaecological cancer that causes thousands of cancer-related deaths in women worldwide; most cervical carcinoma diagnoses occur in developing countries [1]. More than 80% of women have been infected with HPV, but only a small proportion of women develop cervical cancer. This suggests that some other factors may take part in the pathogenesis of cervical cancer. The underlying pathogenesis and progress of cervical cancer is still being investigated
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