Expression of HIF-1α and P-gp in non-small cell lung cancer and the relationship with HPV infection

Lu,Yimin; Yu,Le-Qun; Zhu,Lixia; Zhao,Nian; Zhou,Xing-Ju; Lu,Xudong

doi:10.3892/ol.2016.4751

Expression of HIF-1α and P-gp in non-small cell lung cancer and the relationship with HPV infection

Authors:
- Yimin Lu
- Le-Qun Yu
- Lixia Zhu
- Nian Zhao
- Xing-Ju Zhou
- Xudong Lu
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Affiliations: Department of Pneumology, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China, Department of Gynecology and Obstetrics, The First People's Hospital of Kunshan, Jiangsu University, Kunshan, Jiangsu 215300, P.R. China
Published online on: June 17, 2016 https://doi.org/10.3892/ol.2016.4751
Pages: 1455-1459
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the study was to study the expression of hypoxia-inducible factor-1α (HIF-1α) and P-glycoprotein (P-gp) and analyze its correlation with human papillomavirus (HPV) infection. From January, 2012 to May, 2014, 72 cases of non‑small cell lung cancer (NSCLC) pathologic tissue samples were selected from the study group. Fifty-four lung benign lesions were selected to serve as the control group. HIF-1α and P-gp expression levels were detected using immunohistochemistry. PCR was used to detect the expression of HPV genome employing specific primers for HPV 16 and 18 types. The results showed that there was 47.2 and 63.9% positive HIF-1α and P-gp expression in the study group. No P-gp or HIF-1α expression was detected in the control group. The results established a positive correlation between the expression of HIF-1α and P-gp. In the study group, the expression and differentiation degree of HIF-1α was related to lymphatic metastasis. The HIF-1α expression in the well‑differentiated samples was lower than that in the moderate or poorly differentiated samples. HIF-1α expression in patients with lymphatic metastasis was higher than in patients without metastasis. The expression rate of P-gp in adenocarcinoma was higher than that in squamous carcinoma. The detection rate of HPV DNA was 45.83 and 3.70% in the study and control groups, respectively. The HPV infection and differentiation degree had relevance to lymphatic metastasis in the study group. The HPV DNA detection rate in the well‑differentiated samples was lower than that in the moderate or poorly differentiated samples. The HPV DNA detection rate in patients with lymphatic metastasis was higher than that in patients with no lymphatic metastasis. There was a close link between HIF-1α, P-gp expression and NSCLC occurrence, and the development of multidrug resistance. In conclusion, the detection of HIF-1α and P-gp expression can effectively predict drug resistance during chemotherapy in NSCLC, and these proteins can be used in drug prognosis.

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1	Xie J, Liu J, Liu H, Liang S, Lin M, Gu Y, Liu T, Wang D, Ge H and Mo SL: The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line. Acta Pharm Sin B. 5:554–563. 2015. View Article : Google Scholar : PubMed/NCBI
2	Liang G-K, Yao Z-T, Zhang J-Q, Chen X, Liu R-Y, Chen H-H, Wu H-H, Jin L and Ding L: Statins enhance anti-tumor effect of suberoylanilide hydroxamic acid on human non-small cell lung carcinoma cells. Zhejiang Da Xue Xue Bao Yi Xue Ban. 44:500–505. 2015.(In Chinese). PubMed/NCBI
3	Wei L, Li X and Yu Z: Mutations of EGFR gene and EML4-ALK fusion gene in superficial lymph node of non-small cell lung cancer. Zhonghua Yi Xue Za Zhi. 95:2070–2073. 2015.(In Chinese). PubMed/NCBI
4	Fan H, Shao ZY, Xiao YY, Xie ZH, Chen W, Xie H, Qin GY and Zhao NQ: Incidence and survival of non-small cell lung cancer in Shanghai: a population-based cohort study. BMJ Open. 5:e0094192015. View Article : Google Scholar : PubMed/NCBI
5	Revannasiddaiah S, Joshi SC, Pandey KC, Rastogi M, Sharma M and Gupta M: The results with the addition of metronomic cyclophosphamide to palliative radiotherapy for the treatment of non-small cell lung carcinoma. Ann Transl Med. 3:3052015.PubMed/NCBI
6	Park SY, Yoon JK, Park KJ and Lee SJ: Prediction of occult lymph node metastasis using volume-based PET parameters in small-sized peripheral non-small cell lung cancer. Cancer Imaging. 15:212015. View Article : Google Scholar : PubMed/NCBI
7	Zhao Q, Mao A, Yan J, Sun C, Di C, Zhou X, Li H, Guo R and Zhang H: Downregulation of Nrf2 promotes radiation-induced apoptosis through Nrf2 mediated Notch signaling in non-small cell lung cancer cells. Int J Oncol. 48:765–773. 2016.PubMed/NCBI
8	Dai W, Luo B, Wu Z, Chen J, Feng G and Guan P: A multi-center phase II study of nintedanib as second-line therapy for patients with advanced non-small-cell lung cancer in China. Am J Cancer Res. 5:3270–3275. 2015.PubMed/NCBI
9	Ma L, Wang R, Nan Y, Li W, Wang Q and Jin F: Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases. Int J Oncol. 48:843–853. 2016.PubMed/NCBI
10	Paulsen EE, Kilvaer T, Khanehkenari MR, Maurseth RJ, Al-Saad S, Hald SM, Al-Shibli K, Andersen S, Richardsen E, Busund LT, et al: CD45RO(+) memory T lymphocytes - a candidate marker for TNM-immunoscore in squamous non-small cell lung cancer. Neoplasia. 17:839–848. 2015. View Article : Google Scholar : PubMed/NCBI
11	Imai H, Kaira K, Mori K, Ono A, Akamatsu H, Matsumoto S, Taira T, Kenmotsu H, Harada H, Naito T, et al: Prognostic significance of diabetes mellitus in locally advanced non-small cell lung cancer. BMC Cancer. 15:9892015. View Article : Google Scholar : PubMed/NCBI
12	Cho HJ, Kim HR, Park YS, Kim YH, Kim DK and Park SI: Prognostic value of survivin expression in stage III non-small cell lung cancer patients treated with platinum-based therapy. Surg Oncol. 24:329–334. 2015. View Article : Google Scholar : PubMed/NCBI
13	Chattopadhyay N, Berger AJ, Koenig E, Bannerman B, Garnsey J, Bernard H, Hales P, Maldonado Lopez A, Yang Y, Donelan J, et al: KRAS genotype correlates with proteasome inhibitor ixazomib activity in preclinical in vivo models of colon and non-small cell lung cancer: potential role of tumor metabolism. PLoS One. 10:e01448252015. View Article : Google Scholar : PubMed/NCBI
14	Horinouchi H, Goto Y, Kanda S, Fujiwara Y, Nokihara H, Yamamoto N, Sumi M, Tamura T and Ohe Y: Candidates for intensive local treatment in cIIIA-N2 non-small cell lung cancer: deciphering the heterogeneity. Int J Radiat Oncol Biol Phys. 94:155–162. 2016. View Article : Google Scholar : PubMed/NCBI
15	Deek MP, Benenati B, Kim S, Chen T, Ahmed I, Zou W, Aisner J and Jabbour SK: Thoracic vertebral body irradiation contributes to acute hematologic toxicity during chemoradiation therapy for non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 94:147–154. 2016. View Article : Google Scholar : PubMed/NCBI
16	Vashi PG, Edwin P, Popiel B and Gupta D: The relationship between circulating 25-hydroxyvitamin D and survival in newly diagnosed advanced non-small-cell lung cancer. BMC Cancer. 15:10122015. View Article : Google Scholar : PubMed/NCBI
17	Zhong S, Zhang H, Bai D, Gao D, Zheng J and Ding Y: Detection of ALK, ROS1 and RET fusion genes in non-small cell lung cancer patients and its clinicopathologic correlation. Zhonghua Bing Li Xue Za Zhi. 44:639–643. 2015.(In Chinese). PubMed/NCBI
18	Mullins K: Stereotactic body radiotherapy for early-stage non-small cell lung cancer: when and why is it appropriate therapy? J Adv Pract Oncol. 6:351–354. 2015.PubMed/NCBI
19	Li X, Qin N, Wang J, Yang X, Zhang X, Lv J, Wu Y, Zhang H, Nong J, Zhang Q, et al: Clinical observation of icotinib hydrochloride for advanced non-small cell lung cancer patients with EGFR status identified. Zhongguo Fei Ai Za Zhi. 18:734–739. 2015.(In Chinese). PubMed/NCBI
20	Liang H and Wang M: Mechanism of c-MET in non-small cell lung cancer and its treatment and testing. Zhongguo Fei Ai Za Zhi. 18:745–751. 2015.(In Chinese). PubMed/NCBI
21	Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, Watanabe H, Wu YL, Zielinski M, Ball D, et al: International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Board Members, and Participating Institutions: The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol. 10:1675–1684. 2015. View Article : Google Scholar : PubMed/NCBI
22	Lee C, Usenko D, Frampton GM, McMahon C, Ali SM and Weiss J: MET 14 deletion in sarcomatoid non-small-cell lung cancer detected by next-generation sequencing and successfully treated with a MET inhibitor. J Thorac Oncol. 10:e113–e114. 2015. View Article : Google Scholar : PubMed/NCBI