Abstract
BackgroundCCN family, comprising six members (Cyr61, CTGF, Nov, WISP-1, WISP-2, WISP-3), is involved in the stimulation of cell proliferation, migration, adhesion, angiogenesis, and tumorigenesis. Several studies have shown that expression of Cyr61, CTGF, and WISP-1 affects the tumorigenic potential of lung cancer cells in vitro. However, the correlation of expression of CCN family proteins and clinical features of lung cancer remains unknown.Methodology and Principal FindingsIn the present work, we quantified the mRNA levels of Cyr61, CTGF, and WISP-1 in samples from 60 primary lung cancers and their matched normal lung tissues by quantitative real-time PCR assay. Downregulation of the Cyr61 and CTGF genes and upregulation of the WISP-1 gene were found in primary lung cancers compared to the paired normal lung tissues. Immunohistochemistry analysis also disclosed a similar expression pattern of Cyr61, CTGF, and WISP-1 protein in paired lung cancer tissues. Statistical analysis revealed significant associations between expression of either Cyr61 or CTGF with tumor stage, tumor histology, metastasis, smoking, and family history at diagnosis. A significant correlation also existed between WISP-1 expression with tumor histology, and patient age. Moreover, expression levels of Cyr61 and CTGF correlated with survival of the lung-cancer patients.ConclusionsOur results suggest that Cyr61, CTGF, and WISP-1 might be implicated in the development and progression of primary lung cancers, and their levels might serve as valuable prognostic markers, as well as potential targets for therapeutic intervention.
Highlights
Lung cancer is the most common cause of cancer death in the world [1]
To study the expression pattern of CCN genes in non-small-cell lung carcinoma (NSCLC), levels of cysteinerich protein 61 (Cyr61), connective tissue growth factor (CTGF), and WISP-1 mRNA were quantified in 60 pairs of tumors and their matched normal lung tissues by real-time PCR
Expression level was shown as a ratio between Cyr61, CTGF, or WISP-1 and the reference gene b-actin to correct for the variation in the amounts of RNA
Summary
Lung cancer is the most common cause of cancer death in the world [1]. The majority of lung cancers are non-small-cell lung carcinoma (NSCLC), which is subdivided into adenocarcinoma (AC), squamous-cell carcinoma (SC), and large-cell carcinoma [2]. Several studies have shown that expression of Cyr, CTGF, and WISP-1 affects the tumorigenic potential of lung cancer cells in vitro. The correlation of expression of CCN family proteins and clinical features of lung cancer remains unknown. We quantified the mRNA levels of Cyr, CTGF, and WISP-1 in samples from 60 primary lung cancers and their matched normal lung tissues by quantitative real-time PCR assay. Downregulation of the Cyr and CTGF genes and upregulation of the WISP-1 gene were found in primary lung cancers compared to the paired normal lung tissues. Immunohistochemistry analysis disclosed a similar expression pattern of Cyr, CTGF, and WISP-1 protein in paired lung cancer tissues. A significant correlation existed between WISP-1 expression with tumor histology, and patient age. Our results suggest that Cyr, CTGF, and WISP-1 might be implicated in the development and progression of primary lung cancers, and their levels might serve as valuable prognostic markers, as well as potential targets for therapeutic intervention
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