Independent prognostic value of HIF‑1α expression in radiofrequency ablation of lung cancer

Wan,Jun; Ling,Xiean; Rao,Zhanpeng; Peng,Bin; Ding,Guanggui

doi:10.3892/ol.2019.11130

Independent prognostic value of HIF‑1α expression in radiofrequency ablation of lung cancer

Authors:
- Jun Wan
- Xiean Ling
- Zhanpeng Rao
- Bin Peng
- Guanggui Ding
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Affiliations: Department of Thoracic Surgery, The Shenzhen People's Hospital, The Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong 518020, P.R. China
Published online on: November 21, 2019 https://doi.org/10.3892/ol.2019.11130
Pages: 849-857
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiofrequency ablation (RFA) is widely used in the treatment of lung cancer. Hypoxia‑inducible factor‑1α (HIF‑1α) is a crucial transcription factor regulating oxygen homeostasis that is involved in tumor cell metastasis. The present study investigated the impact of HIF‑1α expression and other factors, such as postoperative blood CD4+/CD8+ ratio, on the prognosis of patients with lung cancer who had received RFA treatment. A total of 80 patients with lung cancer were recruited between January 2011 and October 2016 at The Shenzhen People's Hospital. Lung cancer was confirmed following pathological or histological examination. All patients underwent RFA treatment. Patients were followed up for 6‑66 months. HIF‑1α expression in lung cancer tissues was assessed by immunohistochemistry. Multivariate survival analysis was performed using Cox proportional hazards model. The results demonstrated that HIF‑1α level was low in 36 patients and overexpressed in 44 patients with lung cancer. Kaplan‑Meier (KM) curve analysis demonstrated that the overall survival time of patients with high HIF‑1α expression was significantly shorter compared with patients with low HIF‑1α expression (P<0.05). Furthermore, the results from the KM model and log‑rank test revealed that age, Union for International Cancer Control stage, primary or metastatic cancer, chemotherapy, postoperative blood CD4+/CD8+ ratio, Eastern Cooperative Oncology Group performance status and HIF‑1α expression had significant effects on overall survival of patients with lung cancer. The results from Cox analysis demonstrated that high HIF‑1α expression, advanced age, clinical staging and chemotherapy were independent risk factors for the prognosis of lung cancer following RFA treatment, and that high HIF‑1α expression was associated with the increased risk (5.91‑fold) of mortality. In conclusion, the present study demonstrated that HIF‑1α expression was increased in lung cancer tissues and was associated with the prognosis of patients with lung cancer who were treated with RFA. These findings suggest that HIF‑1α expression may be considered as a marker for evaluating the prognosis of these patients.

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1	Chen WQ, Zuo TT, Zheng RS, Zeng HM, Zhang SW and He J: Lung cancer incidence and mortality in China in 2013. Zhonghua Zhong Liu Za Zhi. 39:795–800. 2017.(In Chinese). PubMed/NCBI
2	Wang X and Adjei AA: Lung cancer and metastasis: New opportunities and challenges. Cancer Metastasis Rev. 34:169–171. 2015. View Article : Google Scholar : PubMed/NCBI
3	Riihimäki M, Hemminki A, Fallah M, Thomsen H, Sundquist K, Sundquist J and Hemminki K: Metastatic sites and survival in lung cancer. Lung Cancer. 86:78–84. 2014. View Article : Google Scholar : PubMed/NCBI
4	Yan X, Jiao SC, Zhang GQ, Guan Y and Wang JL: Tumor-associated immune factors are associated with recurrence and metastasis in non-small cell lung cancer. Cancer Gene Ther. 24:57–63. 2017. View Article : Google Scholar : PubMed/NCBI
5	Wan J and Wu W: Hyperthermia induced HIF-1α expression of lung cancer through AKT and ERK signaling pathways. J Exp Clin Cancer Res. 35:1192016. View Article : Google Scholar : PubMed/NCBI
6	Zhou H, Chen A, Shen J, Zhang X, Hou M, Li J, Chen J, Zou H, Zhang Y, Deng Q, et al: Long non-coding RNA LOC285194 functions as a tumor suppressor by targeting p53 in non-small celllung cancer. Oncol Rep. 41:15–26. 2019.PubMed/NCBI
7	Sasaki M, Sugio K, Kuwabara Y, Koga H, Nakagawa M, Chen T, Kaneko K, Hayashi K, Shioyama Y, Sakai S and Honda H: Alterations of tumor suppressor genes (Rb, p16, p27 and p53) and an increased FDG uptake in lung cancer. Ann Nucl Med. 17:189–196. 2003. View Article : Google Scholar : PubMed/NCBI
8	Lee TG, Jeong EH, Kim SY, Kim HR, Kim H and Kim CH: Fhit, a tumor suppressor protein, induces autophagy via 14-3-3τ in non-small cell lung cancer cells. Oncotarget. 8:31923–31937. 2017.PubMed/NCBI
9	Wang H, Ye L, Xing Z, Li H, Lv T, Liu H, Zhang F and Song Y: CDCA7 promotes lung adenocarcinoma proliferation via regulating the cell cycle. Pathol Res Pract. 215:1525592019. View Article : Google Scholar : PubMed/NCBI
10	Qian X, Song X, He Y, Yang Z, Sun T, Wang J, Zhu G, Xing W and You C: CCNB2 overexpression is a poor prognostic biomarker in Chinese NSCLC patients. Biomed Pharmacother. 74:222–227. 2015. View Article : Google Scholar : PubMed/NCBI
11	Duan J, Huang W and Shi H: Positive expression of KIF20A indicates poor prognosis of glioma patients. Onco Targets Ther. 9:6741–6749. 2016. View Article : Google Scholar : PubMed/NCBI
12	E L, Lu L, Li L, Yang H, Schwartz LH and Zhao B: Radiomics for classification of lung cancer histological subtypes based on nonenhanced computed tomography. Acad Radiol. 26:1245–1252. 2019. View Article : Google Scholar : PubMed/NCBI
13	Yeo MK, Choi SY, Seong IO, Suh KS, Kim JM and Kim KH: Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma. Hum Pathol. 68:103–111. 2017. View Article : Google Scholar : PubMed/NCBI
14	Haga A, Takahashi W, Aoki S, Nawa K, Yamashita H, Abe O and Nakagawa K: Classification of early stage non-small cell lung cancers on computed tomographic images into histological types using radiomic features: Interobserver delineation variability analysis. Radiol Phys Technol. 11:27–35. 2018. View Article : Google Scholar : PubMed/NCBI
15	Lee G, Lee HY, Park H, Schiebler ML, van Beek EJR, Ohno Y, Seo JB and Leung A: Radiomics and its emerging role in lung cancer research, imaging biomarkers and clinical management: State of the art. Eur J Radiol. 86:297–307. 2017. View Article : Google Scholar : PubMed/NCBI
16	Shen R, Olshen AB and Ladanyi M: Integrative clustering of multiple genomic data types using a joint latent variable model with application to breast and lung cancer subtype analysis. Bioinformatics. 25:2906–2912. 2009. View Article : Google Scholar : PubMed/NCBI
17	Cui H, Seubert B, Stahl E, Dietz H, Reuning U, Moreno-Leon L, Ilie M, Hofman P, Nagase H, Mari B and Kruger A: Tissue inhibitor of metalloproteinases-1 induces a pro-tumourigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene. 34:3640–3650. 2015. View Article : Google Scholar : PubMed/NCBI
18	Person RJ, Tokar EJ, Xu Y, Orihuela R, Ngalame NN and Waalkes MP: Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells. Toxicol Appl Pharmacol. 273:281–288. 2013. View Article : Google Scholar : PubMed/NCBI
19	Goda N, Dozier SJ and Johnson RS: HIF-1 in cell cycle regulation, apoptosis, and tumor progression. Antioxid Redox Signal. 5:467–473. 2003. View Article : Google Scholar : PubMed/NCBI
20	Wan J, Chai H, Yu Z, Ge W, Kang N, Xia W and Che Y: HIF-1α effects on angiogenic potential in human small cell lung carcinoma. J Exp Clin Cancer Res. 30:772011. View Article : Google Scholar : PubMed/NCBI
21	Lee CH, Lee MK, Kang CD, Kim YD, Park DY, Kim JY, Sol MY and Suh KS: Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable Non-small cell lung carcinomas. J Korean Med Sci. 18:196–203. 2003. View Article : Google Scholar : PubMed/NCBI
22	Zhang H, Zhang Z, Xu Y, Xing L, Liu J, Li J and Tan Q: The expression of hypoxia inducible factor 1-alpha in lung cancer and its correlation with P53 and VEGF. J Huazhong Univ Sci Technolog Med Sci. 24:124–127. 2004. View Article : Google Scholar : PubMed/NCBI
23	Khan MN, Haggag YA, Lane ME, McCarron PA and Tambuwala MM: Polymeric Nano-encapsulation of curcumin enhances its anti-cancer activity in breast (MDA-MB231) and lung (A549) cancer cells through reduction in expression of HIF-1α and nuclear p65 (Rel A). Curr Drug Deliv. 15:286–295. 2018. View Article : Google Scholar : PubMed/NCBI
24	Jun W and Jian W: Current progression of radiofrequency ablation (RFA) in clinical application of lung cancer therapy. J Biomater Tissue Eng. 9:417–426. 2019. View Article : Google Scholar
25	Luo W, Zhou P and Li W: Advances in diagnosis and treatment of multiple primary lung cancer. Zhongguo Fei Ai Za Zhi. 18:640–643. 2015.(In Chinese). PubMed/NCBI
26	de Baère T, Aupérin A, Deschamps F, Chevallier P, Gaubert Y, Boige V, Fonck M, Escudier B and Palussiére J: Radiofrequency ablation is a valid treatment option for lung metastases: Experience in 566 patients with 1037 metastases. Ann Oncol. 26:987–991. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hiraki T, Gobara H, Iguchi T, Fujiwara H, Matsui Y and Kanazawa S: Radiofrequency ablation for early-stage nonsmall cell lung cancer. Biomed Res Int. 2014:1520872014. View Article : Google Scholar : PubMed/NCBI
28	Qi H and Fan W: Value of ablation therapy in the treatment of lung metastases. Thorac Cancer. 9:199–207. 2018. View Article : Google Scholar : PubMed/NCBI
29	Li G, Xue M, Chen W and Yi S: Efficacy and safety of radiofrequency ablation for lung cancers: A systematic review and meta-analysis. Eur J Radiol. 100:92–98. 2018. View Article : Google Scholar : PubMed/NCBI
30	Liu B, Ye X, Fan W, Li X, Feng W, Lu Q, Mao Y, Lin Z, Li L, Zhuang Y, et al: Expert consensus for image-guided radiofrequency ablation of pulmonary tumors (2018 version). Zhongguo Fei Ai Za Zhi. 21:76–88. 2018.(In Chinese). PubMed/NCBI
31	Palussière J, Catena V and Buy X: Percutaneous thermal ablation of lung tumors-Radiofrequency, microwave and cryotherapy: Where are we going? Diagn Interv Imaging. 98:619–625. 2017. View Article : Google Scholar : PubMed/NCBI
32	Yamamoto A, Hamamoto S, Matsuoka T, Kageyama K, Jogo A, Sohgawa E, Okuma T, Hamuro M, Toyoshima M, Kawabe J, et al: Spontaneous regression of untreated tumors with immuno-radiofrequency ablation, RF ablation in combination with local injection of OK-432, in a patient with lung metastases of colon cancer. J Vasc Interv Radiol. 28:477–479. 2017. View Article : Google Scholar : PubMed/NCBI
33	Wan J, Wu W and Zhang RQ: Local recurrence of small cell lung cancer following radiofrequency ablation is induced by HIF-1α expression in the transition zone. Oncol Rep. 35:1297–1308. 2016. View Article : Google Scholar : PubMed/NCBI
34	Lin CS, Liu TC, Lee MT, Yang SF and Tsao TC: Independent prognostic value of hypoxia-inducible factor 1-alpha expression in small cell lung cancer. Int J Med Sci. 14:785–790. 2017. View Article : Google Scholar : PubMed/NCBI
35	Shin JW, Cho DG, Choi SY, Park JK, Lee KY and Moon Y: Prognostic factors in stage IIB Non-small cell lung cancer according to the 8th edition of TNM Staging System. Korean J Thorac Cardiovasc Surg. 52:131–140. 2019. View Article : Google Scholar : PubMed/NCBI
36	Beland MD, Wasser EJ, Mayo-Smith WW and Dupuy DE: Primary non-small cell lung cancer: Review of frequency, location, and time of recurrence after radiofrequency ablation. Radiology. 254:301–317. 2010. View Article : Google Scholar : PubMed/NCBI
37	Poch FGM, Rieder C, Ballhausen H, Knappe V, Ritz JP, Gemeinhardt O, Kreis ME and Lehmann KS: Finding optimal ablation parameters for multipolar radiofrequency ablation. Surg Innov. 24:205–213. 2017. View Article : Google Scholar : PubMed/NCBI
38	Prud'homme C, Deschamps F, Moulin B, Hakime A, Al-Ahmar M, Moalla S, Roux C, Teriitehau C, de Baere T and Tselikas L: Image-guided lung metastasis ablation: A literature review. Int J Hyperthermia. 36:37–45. 2019. View Article : Google Scholar : PubMed/NCBI
39	Baisi A, Raveglia F, De Simone M and Cioffi U: Palliative role ofpercutaneous radiofrequency ablation for severe hemoptysisin an elderly patient with inoperable lung cancer. J Thorac Cardiovasc Surg. 140:1196–1197. 2010. View Article : Google Scholar : PubMed/NCBI
40	Tong Y, Yang H, Xu X, Ruan J, Liang M, Wu J and Luo B: Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion. Cancer Sci. 108:753–762. 2017. View Article : Google Scholar : PubMed/NCBI
41	Mees G, Sathekge M, Maes A and Van de Wiele C: Radiolabelled probes targeting tumor hypoxia for personalized medicine. Curr Pharm Des. 20:2308–2318. 2014. View Article : Google Scholar : PubMed/NCBI
42	Wan J, Wu W, Chen Y, Kang N and Zhang R: Insufficient radiofrequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1α signals. Acta Biochim Biophys Sin (Shanghai). 48:371–377. 2016. View Article : Google Scholar : PubMed/NCBI
43	Wan J, Wu W, Huang Y, Ge W and Liu S: Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α. Oncol Rep. 36:659–668. 2016. View Article : Google Scholar : PubMed/NCBI
44	Pinato DJ, Black JR, Trousil S, Dina RE, Trivedi P, Mauri FA and Sharma R: Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: Relationship with the hypoxic response, immune evasion and malignant behavior. Oncoimmunology. 6:e13583322017. View Article : Google Scholar : PubMed/NCBI
45	Cai FF, Xu C, Pan X, Cai L, Lin XY, Chen S and Biskup E: Prognostic value of plasma levels of HIF-1α and PGC-1a in breast cancer. Oncotarget. 7:77793–77806. 2016. View Article : Google Scholar : PubMed/NCBI
46	Wan L, Huang J, Chen J, Wang R, Dong C, Lu S and Wu X: Expression and significance of FOXP1, HIF-1α and VEGF in renal clear cell carcinoma. J BUON. 20:188–195. 2015.PubMed/NCBI
47	Wachters JE, Schrijvers ML, Slagter-Menkema L, Mastik M, de Bock GH, Langendijk JA, Kluin PM, Schuuring E, van der Laan BF and van der Wal JE: Prognostic significance of HIF-1α, CA-IX, and OPN in T1-T2 laryngeal carcinoma treated with radiotherapy. Laryngoscope. 123:2154–2160. 2013. View Article : Google Scholar : PubMed/NCBI
48	Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression ofhypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI
49	Kong J, Kong J, Pan B, Ke S, Dong S, Li X, Zhou A, Zheng L and Sun WB: Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1α/VEGFA. PLoS One. 7:e372662012. View Article : Google Scholar : PubMed/NCBI
50	Morine Y, Shimada M, Utsunomiya T, Imura S, Ikemoto T, Mori H, Hanaoka J, Kanamoto M, Iwahashi S and Miyake H: Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma. Hepatogastroenterology. 58:1439–1444. 2011. View Article : Google Scholar : PubMed/NCBI
51	Kitajima Y and Miyazaki K: The Critical impact of HIF-1α on gastric cancer biology. Cancers (Basel). 5:15–26. 2013. View Article : Google Scholar : PubMed/NCBI
52	Zhao X, Fu X, Blumenthal C, Wang YT, Jenkins MW, Snyder C, Arruda M and Rollins AM: Integrated RFA/PSOCT catheter for real-time guidance of cardiac radio-frequency ablation. Biomed Opt Express. 9:6400–6411. 2018. View Article : Google Scholar : PubMed/NCBI
53	Wu W, Wan J, Xia R, Huang Z, Ni J and Yang M: Functional role of regulatory T cells in B cell lymphoma and related mechanisms. Int J Clin Exp Pathol. 8:9133–9139. 2015.PubMed/NCBI
54	Bagrodia A, Krabbe LM, Gayed BA, Kapur P, Bernstein I, Xie XJ, Wood CG, Karam JA, Weizer AZ, Raman JD, et al: Evaluation of the prognostic significance of altered mammalian target of rapamycin pathway biomarkers in upper tract urothelial carcinoma. Urology. 84:1134–1140. 2014. View Article : Google Scholar : PubMed/NCBI
55	Karagoz B, Bilgi O, Gumus M, Erikci AA, Sayan O, Turken O, Kandemir EG, Oztürk A and Yaylaci M: CD8+CD28-cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol. 27:29–33. 2010. View Article : Google Scholar : PubMed/NCBI
56	Ke X, Zhang S, Xu J, Liu G, Zhang L, Xie E, Gao L, Li D, Sun R, Wang F and Pan S: Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation. Cancer Immunol Immunother. 65:587–599. 2016. View Article : Google Scholar : PubMed/NCBI