ISSN: 2008-2258
Vol 15, No 2 (2022): Spring
Prognostic value of HIF-1α in digestive system malignancies: Evidence from a systematic review and meta-analysis
Gastroenterology and Hepatology from Bed to Bench,
,
https://doi.org/10.22037/ghfbb.vi.2351
Abstract
Background/aims: Numerous studies have demonstrated that hypoxia-inducible factor-1α (HIF-1α) is abnormally expressed in various solid tumors. However, the clinicopathological features and prognostic value of HIF-1α expression in patients with digestive system malignancies remain controversial. Accordingly, this meta-analysis was aimed to evaluate the association of HIF-1α expression with clinicopathological features and overall survival (OS) of patients with digestive system malignancies.
Methods: A literature search in PubMed, Web of Science, and Scopus databases was performed to identify all relevant studies published in English until 15 October 2020. Pooled effect was calculated to evaluate the association between HIF-1α expression and clinicopathological features and overall survival in cancer patients. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence interval (CI) were calculated using either fixed- or random-effects model.
Results: A total of 44 eligible studies with 5,964 patients were included. Pooled results indicated positive correlation of HIF-1α overexpression with poor overall survival (OS) (HR=1.990, 95% CI: 1.615-2.453, P<0.001) and disease free survival (DFS) (HR=1.90, 95% CI: 1.084-3.329, P=0.043). Meta-results showed that HIF-1α level expression was significantly associated with positive lymph node metastasis (OR=1.869, 95% CI: 1.488-2.248, P<0.001), distance metastasis (OR=2.604, 95% CI: 1.500-4.519, P<0.001), tumor stage (OR=1.801, 95% CI: 1.437-2.257, P<0.001) and tumor size (OR=1.392. 95% CI: 1.068-1.815, P=0.014).
Conclusions: This meta-data suggest that HIF-1α expression might serve as an independent prognostic marker and a promising therapeutic target in patients with digestive system malignancies.
Keywords:
- HIF-1α; cancer; digestive system; prognosis
References
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4. Mohammadi M, Mianabadi F, Mehrad‐Majd H. Circulating visfatin levels and cancers risk: A systematic review and meta‐analysis. Journal of cellular physiology. 2019;234(4):5011-22.
5. Arjmand M-H, Moradi A, Akbari A, Mehrad-Majd H. Clinical significance of circulating omentin levels in various malignant tumors: Evidence from a systematic review and meta-analysis. Cytokine. 2020;125:154869.
6. Banin Hirata BK, Oda JMM, Losi Guembarovski R, Ariza CB, Oliveira CECd, Watanabe MAE. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior. Disease Markers. 2014;2014:513158.
7. Harris AL. Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2(1):38-47.
8. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721-32.
9. Dai C-X, Gao Q, Qiu S-J, Ju M-J, Cai M-Y, Xu Y-F, et al. Hypoxia-inducible factor-1 alpha, in association with inflammation, angiogenesis and MYC, is a critical prognostic factor in patients with HCC after surgery. BMC cancer. 2009;9(1):418.
10. Wigerup C, Påhlman S, Bexell D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacology & therapeutics. 2016;164:152-69.
11. Ping W, Sun W, Zu Y, Chen W, Fu X. Clinicopathological and prognostic significance of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma: a meta-analysis. Tumor Biology. 2014;35(5):4401-9.
12. Ogawa K, Chiba I, Morioka T, Shimoji H, Tamaki W, Takamatsu R, et al. Clinical significance of HIF-1α expression in patients with esophageal cancer treated with concurrent chemoradiotherapy. Anticancer research. 2011;31(6):2351-9.
13. Ogane N, Yasuda M, Shimizu M, Miyazawa M, Kamoshida S, Ueda A, et al. Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma. Annals of diagnostic pathology. 2010;14(1):23-9.
14. Kuwai T, Kitadai Y, Tanaka S, Onogawa S, Matsutani N, Kaio E, et al. Expression of hypoxia‐inducible factor‐1α is associated with tumor vascularization in human colorectal carcinoma. International journal of cancer. 2003;105(2):176-81.
15. Kwon HC, Kim SH, Oh SY, Lee S, Kwon KA, Lee JH, et al. Clinicopathological significance of nuclear factor‐kappa B, HIF‐1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer. Cancer science. 2010;101(6):1557-61.
16. Ma J, Zhang L, Ru G-Q, Zhao Z-S, Xu W-J. Upregulation of hypoxia inducible factor 1α mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma. World journal of gastroenterology: WJG. 2007;13(11):1680.
17. Hu X, Lin S, Zheng J, Guo R, Li H, You C. Clinicopathological significance of hypoxia-inducible factor-1 alpha polymorphisms in cancers: evidence from a meta-analysis. Tumor Biology. 2013;34(5):2477-87.
18. Zhang J, Wu Y, Lin Y-H, Guo S, Ning P-F, Zheng Z-C, et al. Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer. World journal of gastroenterology. 2018;24(22):2381.
19. Sun H-C, Qiu Z-J, Liu J, Sun J, Jiang T, Huang K-J, et al. Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis. International journal of oncology. 2007;30(6):1359-67.
20. Xiang Z-L, Zeng Z-C, Fan J, Tang Z-Y, He J, Zeng H-Y, et al. The expression of HIF-1α in primary hepatocellular carcinoma and its correlation with radiotherapy response and clinical outcome. Molecular biology reports. 2012;39(2):2021-9.
21. Yang SL, Liu LP, Jiang JX, Xiong ZF, He QJ, Wu C. The correlation of expression levels of HIF-1α and HIF-2α in hepatocellular carcinoma with capsular invasion, portal vein tumor thrombi and patients' clinical outcome. Jpn J Clin Oncol. 2014;44(2):159-67.
22. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. European journal of epidemiology. 2010;25(9):603-5.
23. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in medicine. 1998;17(24):2815-34.
24. Williamson PR, Smith CT, Hutton JL, Marson AG. Aggregate data meta‐analysis with time‐to‐event outcomes. Statistics in medicine. 2002;21(22):3337-51.
25. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8(1):16.
26. Galbraith RF. A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med. 1988;7(8):889-94.
27. Chen L, Shi Y, Yuan J, Han Y, Qin R, Wu Q, et al. HIF-1 alpha overexpression correlates with poor overall survival and disease-free survival in gastric cancer patients post-gastrectomy. PLoS One. 2014;9(3):e90678.
28. Lu X-X, Chen Y-T, Feng B, Mao X-B, Yu B, Chu X-Y. Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma. World journal of gastroenterology: WJG. 2013;19(12):1912.
29. Isobe T, Aoyagi K, Koufuji K, Shirouzu K, Kawahara A, Taira T, et al. Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer. International journal of clinical oncology. 2013;18(2):293-304.
30. Qiu M-z, Han B, Luo H-y, Zhou Z-w, Wang Z-q, Wang F-h, et al. Expressions of hypoxia-inducible factor-1α and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features. Tumor Biology. 2011;32(1):159-66.
31. Oh SY, Kwon H-C, Kim S-H, Jang JS, Kim MC, Kim KH, et al. Clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer. BMC cancer. 2008;8(1):123.
32. KolevY U, TakagiY S. Lactate Dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-Inducible factor (HIF-1a) pathway, angiogenic factors production and poor prognosis. Ann surg oncol. 2008;15(8):2336-44.
33. Griffiths EA, Pritchard S, Valentine HR, Whitchelo N, Bishop P, Ebert M, et al. Hypoxia-inducible factor-1 α expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas. British journal of cancer. 2007;96(1):95-103.
34. Sumiyoshi Y, Kakeji Y, Egashira A, Mizokami K, Orita H, Maehara Y. Overexpression of hypoxia-inducible factor 1α and p53 is a marker for an unfavorable prognosis in gastric cancer. Clinical cancer research. 2006;12(17):5112-7.
35. Urano N, Fujiwara Y, Doki Y, Tsujie M, Yamamoto H, Miyata H, et al. Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric cancer. 2006;9(1):44-9.
36. Mizokami K, Kakeji Y, Oda S, Irie K, Yonemura T, Konishi F, et al. Clinicopathologic significance of hypoxia‐inducible factor 1α overexpression in gastric carcinomas. Journal of surgical oncology. 2006;94(2):149-54.
37. Saka B, Ekinci O, Dursun A, Akyurek N. Clinicopathologic and prognostic significance of immunohistochemical expression of HIF-1α, CXCR4 and CA9 in colorectal carcinoma. Pathology-Research and Practice. 2017;213(7):783-92.
38. Shimomura M, Hinoi T, Kuroda S, Adachi T, Kawaguchi Y, Sasada T, et al. Overexpression of hypoxia inducible factor-1 alpha is an independent risk factor for recurrence after curative resection of colorectal liver metastases. Annals of surgical oncology. 2013;20(3):527-36.
39. Xie YQ, Fu D, He ZH, Tan QD. Prognostic value of Annexin A3 in human colorectal cancer and its correlation with hypoxia‑inducible factor‑1α. Oncology letters. 2013;6(6):1631-5.
40. Shioya M, Takahashi T, Ishikawa H, Sakurai H, Ebara T, Suzuki Y, et al. Expression of hypoxia-inducible factor 1α predicts clinical outcome after preoperative hyperthermo-chemoradiotherapy for locally advanced rectal cancer. Journal of radiation research. 2011;52(6):821-7.
41. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Koike Y, et al. Clinical significance of CD133 and hypoxia inducible factor-1α gene expression in rectal cancer after preoperative chemoradiotherapy. Clinical Oncology. 2011;23(5):323-32.
42. Baba Y, Nosho K, Shima K, Irahara N, Chan AT, Meyerhardt JA, et al. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. The American journal of pathology. 2010;176(5):2292-301.
43. Cao D, Hou M, Guan Y-s, Jiang M, Yang Y, Gou H-f. Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications. BMC cancer. 2009;9(1):432.
44. Jubb A, Turley H, Moeller H, Steers G, Han C, Li J, et al. Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. British journal of cancer. 2009;101(10):1749-57.
45. Rajaganeshan R, Prasad R, Guillou P, Scott N, Poston G, Jayne D. Expression patterns of hypoxic markers at the invasive margin of colorectal cancers and liver metastases. European Journal of Surgical Oncology (EJSO). 2009;35(12):1286-94.
46. Rasheed S, Harris A, Tekkis P, Turley H, Silver A, McDonald P, et al. Hypoxia-inducible factor-1α and-2α are expressed in most rectal cancers but only hypoxia-inducible factor-1α is associated with prognosis. British journal of cancer. 2009;100(10):1666-73.
47. Lu X-g, Xing C-g, Feng Y-z, Chen J, Deng C. Clinical significance of immunohistochemical expression of hypoxia-inducible Factor–1α as a prognostic marker in rectal adenocarcinoma. Clinical colorectal cancer. 2006;5(5):350-3.
48. Theodoropoulos GE, Lazaris AC, Theodoropoulos VE, Papatheodosiou K, Gazouli M, Bramis J, et al. Hypoxia, angiogenesis and apoptosis markers in locally advanced rectal cancer. International journal of colorectal disease. 2006;21(3):248-57.
49. Yoshimura H, Dhar DK, Kohno H, Kubota H, Fujii T, Ueda S, et al. Prognostic impact of hypoxia-inducible factors 1α and 2α in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression. Clinical cancer research. 2004;10(24):8554-60.
50. Kuwai T, Kitadai Y, Tanaka S, Kuroda T, Ochiumi T, Matsumura S, et al. Single nucleotide polymorphism in the hypoxia-inducible factor-1α gene in colorectal carcinoma. Oncology reports. 2004;12(5):1033-7.
51. Chen Y, Lu Y, Lu C, Zhang L. Beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1α expression. Pathology & Oncology Research. 2009;15(3):487.
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