Abstract

We investigated the expression of epithelial Ca2+ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection. From January 2008 to January 2009, 145 patients who had undergone surgical resection of NSCLCs were enrolled in the study. Patient clinical characteristics were retrospectively reviewed. Fresh tumor samples as well as peritumor tissues were analyzed for TRPV5/6 expression using immune-histochemistry (IHC) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were grouped based on their TRPV5 and TRPV6 levels in the tumor tissues, followed up after surgery, and statistically analyzed to examine the prognostic roles of TRPV5 and TRPV6 on patients' survival after surgical resection of NSCLCs. Using IHC, among the 145 patients who had undergone surgical resection of NSCLCs, strong protein expression (grade ≥ 2) of TRPV5 and TRPV6 was observed in a lower percentage of primary tumor tissues than in non-tumor tissues of same patients. Similar findings were obtained with the RT-PCR test for mRNA levels. Decreased overall mRNA levels of TRPV5 and TRPV6 were associated with a worse overall survival rate (p=0.004 and p=0.003 respectively) and shorter recurrence-free survival (p?0.001 and p?0.001 respectively). The combining effect of TRPV5 and TRPV6 on survival was further investigated using multivariate analysis. The results showed that a combination of low expression of TRPV5 and TRPV6 could be an independent predictor of poor recurrence-free survival (p=0.002). Decreased expression of TRPV5/6 in tumor tissues was observed in NSCLC patients and was associated with shorter median survival time after surgical resection. Combined expression of TRPV5 and TRPV6 in tumor tissues demonstrated promising prognostic value in NSCLC patients.

Highlights

  • Lung is one of the four major cancer sites namely lung, breasts, colorectum and prostate

  • We investigated the expression of epithelial Ca2+ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection

  • The Expression of TRPV 5 and TRPV 6 in cancer tissues and corresponding normal tissues In reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, TRPV5 mRNAwas less expressed in tumor tissue than in normal tissue (0.00008935±0.00001347 versus 0.00026770±0.00010989, p=0.013)

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Summary

Introduction

Lung is one of the four major cancer sites namely lung, breasts, colorectum and prostate. Lung cancer is always asymptomatic in its early stage and in most cases it would not be diagnosed until it advances into terminal stage, bringing much more difficulty to treatment. These facts have made it important to look for reliable biomarkers for early diagnosis of lung cancer. Belonging to the transient receptor potential (TRP) superfamily along with six other subfamilies, namely, the TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPN (no mechanoreceptor potential C, NOMPC) and TRPP (polycystin), TRPV5 and TRPV6 are highly homologous members of the TRPV (vanilloid) subfamily (Vennekens et al, 2002; OuadidAhidouch et al, 2013). The large and functionally versatile TRP superfamily consists of various cation channel proteins expressed in numerous cell types from yeast to mammals. The large and functionally versatile TRP superfamily consists of various cation channel proteins expressed in numerous cell types from yeast to mammals. (Lehen’kyi et al, 2012) These channels were first identified in Drosophila melanogaster (Minke, 1977; Montell et al, 1985)

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