胃癌组织中HIF-1α,CD68及CD206在胃癌及癌旁组织中的表达及临床意义

doi:10.3969/j.issn.1009-976X.2021.01.015

摘要/Abstract

摘要： 目的分析低氧诱导分子-1α（HIF-1α）及肿瘤相关巨噬细胞（TAM）相关抗原CD68、CD206在胃癌及癌旁组织中的表达情况。方法利用免疫组化技术检测43例胃癌和癌旁组织中HIF-1α、CD68、CD206的表达状态,计算三种蛋白表达的阳性率及阳性细胞数,揭示其与临床因素的相关性。结果 HIF-1α、CD68、CD206的阳性表达率分别为58.1%、69.8%、51.2%,均高于癌旁组织（P<0.05）。胃癌、癌旁组织中每个视野下CD68⁺细胞数分别为（39.7±7.6）、（8.5±2.8）个;CD206⁺阳性细胞数分别为（32.0±9.2）、（3.4±1.8）个;HIF-1α⁺细胞数（22.9±5.6）、（2.1±1.2）个;组间比较差异均有统计学意义（P<0.01）。胃癌组织中CD206⁺细胞数与HIF-1α⁺细胞数表达呈正相关（P<0.01,R²=0.641）。三种蛋白的表达与胃癌病理分期、淋巴结转移明显相关（P<0.05）。结论胃癌组织中CD68、CD206、HIF-1α表达率及阳性细胞数明显增加,且CD206与HIF-1α表达呈正相关。胃癌缺氧区域对M2型巨噬细胞有趋化作用,促进胃癌发生发展。

关键词: 胃癌, 缺氧诱导因子, 肿瘤相关巨噬细胞, CD68, CD206

Abstract: Objective To analyze the expression of hypoxic-induced molecule-1 α（HIF-1α） and tumor-associated macrophages （TAM） related antigens CD68 and CD206 in gastric cancer and adjacent tissues. Methods Immunohistochemistry was used to detect the expression status of HIF-1α, CD68 and CD206 in 43 cases of gastric cancer and adjacent tissues, and the positive rate and number of positive cells of the three proteins were calculated to reveal their correlation with clinical factors. Results The positive expression rates of HIF-1, CD68 and CD206 were 58.1%, 69.8% and 51.2%, respectively, which were higher than that of adjacent tissues （P<0.05）. In gastric cancer and adjacent tissues, the number of CD68⁺ cells in each field was （39.7±7.6） and （8.5±2.8）, respectively; the number of CD206⁺ positive cells was （32.0±9.2） and （3.4±1.8）, respectively; the number of HIF-1α⁺ cells was （22.9±5.6） and （2.1±1.2）, respectively; the differences between groups were statistically significant （P<0.01）. The number of CD206⁺ cells in gastric cancer tissues was positively correlated with the expression of HIF-1α⁺ cells （P<0.01,R²=0.641）. The expression of the three proteins was related to pathological stage and lymph node metastasis（P<0.05）. Conclusion The expression rates and the number of positive cells of CD68, CD206 and HIF-1αin gastric cancer tissues were significantly increased, and CD206 was positively correlated with the expression of HIF-1α. The hypoxia area of gastric cancer has chemotaxis effect on M2 macrophages and promotes the occurrence and development of gastric cancer.

Key words: gastric cancer, hypoxia induction factor, tumor-associated macrophages, CD68, CD206

中图分类号:

R735.2

周太成, 马宁, 黄恩民, 马涛, 陈嘉林, 陈双. 胃癌组织中HIF-1α,CD68及CD206在胃癌及癌旁组织中的表达及临床意义[J]. 岭南现代临床外科, 2021, 21(01): 87-90.

ZHOU Tai-cheng, TANG Fu-xin, MA Ning, HUANG En-min, MA Tao, CHEN Jia-lin, CHEN Shuang. Expression of HIF-1, CD68 and CD206 in gastric cancer and its clinical significance[J]. Lingnan Modern Clinics In Surgery, 2021, 21(01): 87-90.

参考文献

[1] Su CY, Fu XL, Duan W, et al.High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression[J]. Oncol Lett, 2018, 15(5):6217-6224.
[2] Brahimi-Horn MC, Chiche J, Pouysségur J.Hypoxia and cancer[J]. J Mol Med (Berlin, Germany), 2007, 85(12):1301-1307.
[3] Paget S.The distribution of secondary growths in cancer of the breast. 1889[J]. Cancer Metastasis Rev, 1989, 8(2):98-101.
[4] Turley SJ, Cremasco V, Astarita JL.Immunological hallmarks of stromal cells in the tumour microenvironment[J]. Nat Rev Immunol, 2015, 15:669-682.
[5] Zhang WJ, Chen C, Zhou ZH, et al.Hypoxia-inducible factor-1 alpha Correlates with Tumor-Associated Macrophages Infiltration, Influences Survival of Gastric Cancer Patients[J]. J Cancer, 2017, 8(10):1818-1825.
[6] Allavena P, Sica A, Solinas G,et al.The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages[J]. Crit Rev Oncol Hematol, 2008, 66(1):1-9.
[7] Gentles AJ, Newman AM, Liu CL, et al.The prognostic landscape of genes and infiltrating immune cells across human cancers[J]. Nat Med, 2015, 21(8):938-945.
[8] Osinsky S, Bubnovskaya L, Ganusevich I, et al.Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival[J]. Clin Transl Oncol, 2011, 13(2):133-138.
[9] Mantovani A, Schioppa T, Porta C, et al.Role of tumor-associated macrophages in tumor progression and invasion[J]. Cancer Metastasis Rev, 2006, 25(3):315-322.
[10] Rohwer N, Cramer T.HIFs as central regulators of gastric cancer pathogenesis[J]. Cancer Biol Ther, 2010, 10(4):383-385.
[11] Isobe T, Aoyagi K, Koufuji K, et al.Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer[J]. Int J Clin Oncol, 2013, 18(2):293-304.
[12] Henze AT, Mazzone M.The impact of hypoxia on tumor-associated macrophages[J]. J Clin Invest, 2016, 126(10):3672-3679.
[13] Jamiyan T, Kuroda H, Yamaguchi R, et al.CD68- and CD163-positive tumor-associated macrophages in triple negative cancer of the breast[J]. Virchows Arch, 2020, 477(6):767-775.
[14] Lissbrant IF, Stattin P, Wikstrom P, et al.Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival[J]. Int J Oncol, 2000, 17(3):445-451.
[15] Kerr KM, Johnson SK, King G, et al.Partial regression in primary carcinoma of the lung: does it occur?[J]. Histopathology, 1998, 33(1):55-63.
[16] Leung SY, Wong MP, Chung LP, et al.Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas[J]. Acta Neuropathol, 1997, 93(3):518-527.
[17] Riethdorf L, Riethdorf S, Gützlaff K, et al.Differential expression of the monocyte chemoattractant protein-1 gene in human papillomavirus-16-infected squamous intraepithelial lesions and squamous cell carcinomas of the cervix uteri[J]. Am J Pathol, 1996, 149(5):1469-1476.
[18] Boström MM, Irjala H, Mirtti T, et al.Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer[J]. PLoS One, 2015, 10(7):e0133552.
[19] Jubb AM, Soilleux EJ, Turley H, et al.Expression of vascular notch ligand delta-like 4 and inflammatory markers in breast cancer[J]. Am J Pathol, 2010, 176(4):2019-2028.
[20] Fu XL, Duan W, Su CY, et al.Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression[J]. Cancer Immunol Immunother, 2017, 66(12):1597-1608.