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The expression of V-ATPase is associated with drug resistance and pathology of non-small-cell lung cancer

Qiang Lu1, Sha Lu2, Lijun Huang1, Ting Wang3, Yi Wan4, Chang Xi Zhou5, Cunhai Zhang6, Zhipei Zhang1* and Xiaofei Li1*

Author affiliations

1 Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, 710038 Xi’an, PR China

2 Department of Intensive Care Unit, Xi’an Central Hospital, Xi’an, China

3 Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

4 Department of Health Statistics & Institute for Health Informatics, Fourth Military Medical University, Xi’an, China

5 Department of Nanlou Respiratory Diseases, PLA General Hospital, Beijing, China

6 Department of Intensive Care Unit, 117th Hospital of PLA, Hangzhou, China

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Citation and License

Diagnostic Pathology 2013, 8:145  doi:10.1186/1746-1596-8-145

Published: 28 August 2013

Abstract

Objective

This article aims to investigate the expression of vacuolar-H + −ATPase (V-ATPase) in non-small cell lung cancer (NSCLC) and its variations with pathological type and grade. Furthermore, to evaluate the chemotherapy drug sensitivity of different cancer tissues as well as its correlation with V-ATPase expression in NSCLC.

Methods

V-ATPase expression was examined in 92 NSCLC tissue samples using the immunohistochemical Envision method and immunofluorescence assay. The location of V-ATPase expression was observed by confocal laser scanning microscopy and the difference of its expression rate was evaluated. The sensitivity of cancer tissues to chemotherapy drug was examined using MTT assay and its correlation with the V-ATPase expression was tested in NSCLC by Spearman rank correlation analysis.

Results

V-ATPase expression was mainly localized in the cell membrane and cytoplasm. The expression rate of V-ATPase was 71.43% in squamous cell lung cancer, significantly lower than that of the lung adenocarcinoma (83.72%, P = 0.000). In different pathological grades of squamous cell lung cancer, the expression rate of V-ATPase was 58.33% in grade II, significantly lower than that of the grade III (84.00%, P = 0.014). The expression rate of V-ATPase in grade II lung adenocarcinoma was 76.67%, significantly lower than that of the grade ΙΙΙ adenocarcinoma (100.0%, P = 0.012). Correlation analysis showed that the sensitivity of NSCLC tissues to cyclophosphamide, gemcitabine, doxorubicin, paclitaxel and cisplatin was significantly correlated with the V-ATPase expression rate (P < 0.05).

Conclusions

V-ATPase was overexpressed in NSCLC. The expression of V-ATPase was related to the pathological type and grade of cancer and was likely associated with chemotherapy drug resistance in NSCLC.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7515811511020000 webcite

Keywords:
Non-small cell lung cancer; V-ATPase; Drug resistance; Drug sensitivity