Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis

Abstract

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.

Keywords

non-small cell lung cancer / small cell lung cancer / hypoxia-inducible factor-1 alpha / vascular endothelial growth factor / epidermal growth factor receptor

References

[1] SiegelR, NaishadhamD, JemalA. Cancer statistics, 2013. CA Cancer J Clin, 2013, 63(1): 11-30 PMID: 23335087

[2] SiegelR, DeSantisC, VirgoK, et al. . Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin, 2012, 62(4): 220-241 PMID: 22700443

[3] ZhongH, SemenzaGL, SimonsJW, et al. . Up-regulation of hypoxia-inducible factor 1alpha is an early event in prostate carcinogenesis. Cancer Detect Prev, 2004, 28(2): 88-93 PMID: 15068831

[4] VolmM, KoomagiR. Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer. Anticancer Res, 2000, 20(3): 1527-1533 PMID: 10928066

[5] GiatromanolakiA, OukourakisM, SivridisE, et al. . Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer, 2001, 85(6): 881-890 PMID: 11556841 PMCID: 2375073

[6] LeeCH, LeeMK, KangCD, et al. . 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, 2003, 18(2): 196-203 PMID: 12692416 PMCID: 3055010

[7] HiramiY, AoeM, TsukudaK, et al. . Relation of epidermal growth factor receptor, phosphorylated-Akt, and hypoxia-inducible factor-1alpha in non-small cell lung cancers. Cancer Lett, 2004, 214(2): 157-164 PMID: 15363541

[8] SwinsonDE, JonesJL, CoxG, et al. . Hypoxia-inducible factor-1 alpha in non small cell lung cancer: relation to growth factor, protease and apoptosis pathways. Int J Cancer, 2004, 111(1): 43-50 PMID: 15185341

[9] KimSJ, RabbaniZN, DewhirstMW, et al. . Expression of HIF-1alpha, CAIX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer, 2005, 49(3): 325-335 PMID: 15935515

[10] EnatsuS, IwasakiA, ShirakusaT, et al. . Expression of hypoxia-inducible factor-1 alpha and its prognostic significance in small-sized adenocarcinomas of the lung. Eur J Cardiothorac Surg, 2006, 29(6): 891-895 PMID: 16675263

[11] ZuoS, JiY, WangJ, et al. . Expression and clinical implication of HIF-1alpha and VEGF-C in non-small cell lung cancer. J Huazhong Univ Sci Technolog Med Sci, 2008, 28(6): 674-676 PMID: 19107364

[12] ChenYQ, ZhaoCL, LiW. Effect of hypoxia-inducible factor-1alpha on transcription of survivin in non-small cell lung cancer. J Exp Clin Cancer Res, 2009, 28(1): 29 PMID: 19245702 PMCID: 2663545

[13] HungJJ, YangMH, HsuHS, et al. . Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer. Thorax, 2009, 64(12): 1082-1089 PMID: 19778933

[14] IoannouM, PapamichaliR, KouvarasE, et al. . Hypoxia inducible factor-1 alpha and vascular endothelial growth factor in biopsies of small cell lung carcinoma. Lung, 2009, 187(5): 321-329 PMID: 19707816

[15] YohenaT, YoshinoI, TakenakaT, et al. . Upregulation of hypoxia-inducible factor-1alpha mRNA and its clinical significance in non-small cell lung cancer. J Thorac Oncol, 2009, 4(3): 284-290 PMID: 19190516

[16] AndersenS, EilertsenM, DonnemT, et al. . Diverging prognostic impacts of hypoxic markers according to NSCLC histology. Lung Cancer, 2011, 72(3): 294-302 PMID: 21075472

[17] ParkS, HaSY, ChoHY, et al. . Prognostic implications of hypoxia-inducible factor-1alpha in epidermal growth factor receptor-negative non-small cell lung cancer. Lung Cancer, 2011, 72(1): 100-107 PMID: 20822827

[18] WuXH, QianC, YuanK. Correlations of hypoxia-inducible factor-1alpha/hypoxia-inducible factor-2alpha expression with angiogenesis factors expression and prognosis in non-small cell lung cancer. Chin Med J (Engl), 2011, 124(1): 11-18

[19] KaretsiE, IoannouMG, KerenidiT, et al. . Differential expression of hypoxia-inducible factor 1alpha in non-small cell lung cancer and small cell lung cancer. Clinics (Sao Paulo), 2012, 67(12): 1373-1378

[20] LeeGW, GoSI, ChoYJ, et al. . Hypoxia-inducible factor-1alpha and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: a retrospective study. J Thorac Oncol, 2012, 7(3): 528-534 PMID: 22258474

[21] MunksgaardPM, JohanssonME, MonsefN, et al. . HIF-2alpha expression is suppressed in SCLC cells, which survive in moderate and severe hypoxia when HIF-1alpha is repressed. Am J Pathol, 2012, 180(2): 494-504

[22] LuanY, GaoC, MiaoY, et al. . Clinicopathological and prognostic significance of HIF-1alpha and HIF-2alpha expression in small cell lung cancer. Pathol Res Pract, 2013, 209(3): 184-189 PMID: 23375698

[23] PingW, JiangWY, ChenWS, et al. . Expression and significance of hypoxia inducible factor-1alpha and lysyl oxidase in non-small cell lung cancer. Asian Pac J Cancer Prev, 2013, 14(6): 3613-3618 PMID: 23886154

[24] MinakataK, TakahashiF, NaraT, et al. . Hypoxia induces gefitinib resistance in non-small-cell lung cancer with both mutant and wild-type epidermal growth factor receptors. Cancer Sci, 2012, 103(11): 1946-1954 PMID: 22863020

[25] HongueroMA, ArnauOA, FigueroaAS, et al. . Prognostic value of the expression of vascular endothelial growth factor A and hypoxia-inducible factor 1alpha in patients undergoing surgery for non-small cell lung cancer. Med Clin (Barc), 2014, 142(10): 432-437

[26] StroupDF, BerlinJA, MortonSC, et al. . Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA, 2000, 283(15): 2008-2012 PMID: 10789670

[27] HigginsJP, ThompsonSG, DeeksJJ, et al. . Measuring inconsistency in meta-analyses. BMJ, 2003, 327(7414): 557-560 PMID: 12958120 PMCID: 192859

[28] DerSimonianR, LairdN. Meta-analysis in clinical trials. Control Clin Trials, 1986, 7(3): 177-188 PMID: 3802833

[29] LauSK, BoutrosPC, PintilieM, et al. . Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol, 2007, 25(35): 5562-5569 PMID: 18065728

[30] JubbAM, PhamTQ, HanbyAM, et al. . Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. J Clin Pathol, 2004, 57(5): 504-512 PMID: 15113858 PMCID: 1770303

[31] GhattassK, AssahR, El-SabbanM, et al. . Targeting hypoxia for sensitization of tumors to radio-and chemotherapy. Curr Cancer Drug Targets, 2013, 13(6): 670-685 PMID: 23687923

[32] CaoS, YangS, WuC, et al. . Protein expression of hypoxia-inducible factor-1 alpha and hepatocellular carcinoma: a systematic review with meta-analysis. Clin Res Hepatol Gastroenterol, 2014, 38(5): 598-603 PMID: 24835771

[33] BabaY, NoshoK, ShimaK, et al. . HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol, 2010, 176(5): 2292-2301 PMID: 20363910 PMCID: 2861094

[34] HoffmannAC, MoriR, VallbohmerD, et al. . High expression of HIF1a is a predictor of clinical outcome in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA, VEGF, and bFGF. Neoplasia, 2008, 10(7): 674-679 PMID: 18592007 PMCID: 2435004

[35] TangCM, YuJ. Hypoxia-inducible factor-1 as a therapeutic target in cancer. J Gastroenterol Hepatol, 2013, 28(3): 401-405 PMID: 23173651

[36] ChenD, ZhangYJ, ZhuKW, et al. . A systematic review of vascular endothelial growth factor expression as a biomarker of prognosis in patients with osteosarcoma. Tumour Biol, 2013, 34(3): 1895-1899 PMID: 23589053

[37] LoHW. Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications. Discov Med, 2010, 10(50): 44-51 PMID: 20670598 PMCID: 3637667

[38] PengXH, KarnaP, CaoZ, et al. . Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem, 2006, 281(36): 25903-25914 PMID: 16847054 PMCID: 3132567

[39] SwinsonDE, O'ByrneKJ. Interactions between hypoxia and epidermal growth factor receptor in non-small-cell lung cancer. Clin Lung Cancer, 2006, 7(4): 250-256 PMID: 16512978