Differential expression of IL-8 in triple negative breast cancer and its clinical significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TANG Yunhui , HOU Lingmi , QIAN Shuangqiang , CHEN Jingtai , PU Hongyu ,  GAO Yanchun

Department of Thyroid and Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;

Corresponding author：

GAO Yanchun, Email: boyang11111@163.com

Keywords：

triple negative breast cancer; interleukin-8; inflammatory cytokine

DOI：

10.7507/1007-9424.202103026

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the relationship between the expression of IL-8 protein in triple negative breast cancer (TNBC) and clinicopathological features and survival prognosis.Methods The expression of IL-8 protein in 80 cases of TNBC was detected by immunohistochemical staining, and the relationship between the expression of IL-8 protein and clinicopathological features and prognosis of TNBC patients was analyzed by χ² test, log-rank test, and Cox proportional hazards regression.Results In 80 TNBC patients, the high expression of IL-8 protein accounted for 22.5% (18/80). The expression level of IL-8 protein in TNBC tumor tissue was correlated with T stage, clinical stage, Ki-67 expression, WHO grade and lymph node metastasis (P<0.05). However, it was not related to age, menopausal status, pathological type of tumor and whether they had received neoadjuvant chemotherapy (P>0.05). The results of log-rank analysis showed that the disease-free survival rate (DFS) of high expression group of IL-8 protein was poor than that of low expression group of IL-8 protein (P<0.05). Multivariate Cox proportional hazards regression analysis showed that the expression of IL-8 protein was an independent factor affecting the survival and prognosis of TNBC patients [HR=1.180, 95%CI (1.001, 1.391), P=0.049]. The prognosis of TNBC patients with high expression of IL-8 protein was poor.Conclusion The expression level of IL-8 protein is an independent risk factor affecting the survival and prognosis of patients with TNBC.

Citation： TANG Yunhui, HOU Lingmi, QIAN Shuangqiang, CHEN Jingtai, PU Hongyu, GAO Yanchun. Differential expression of IL-8 in triple negative breast cancer and its clinical significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(11): 1462-1468. doi: 10.7507/1007-9424.202103026 Copy

1.	陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况. 中国肿瘤临床, 2015, 42(13): 668-674.
2.	Clinton SK, Giovannucci EL, Hursting SD. The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions. J Nutr, 2020, 150(4): 663-671.
3.	Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med, 2010, 363(20): 1938-1948.
4.	牟成金, 潘武, 李娟, 等. 干扰 IL-8 表达对乳腺癌细胞侵袭、迁移能力的影响. 免疫学杂志, 2018, 34(9): 765-771.
5.	Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res, 2008, 14(21): 6735-6741.
6.	柴瑛. 骨肉瘤患者白细胞介素 8 表达及其对骨肉瘤细胞增殖、迁移的作用和机制. 中国老年学杂志, 2018, 38(10): 2475-2476.
7.	罗先荣, 彭家清, 熊燕, 等. IL-8 通过下调 miR-199a-3p 对肾癌细胞迁移、侵袭及上皮-间质转化的影响. 免疫学杂志, 2019, 35(12): 1037-1042.
8.	Cheng XS, Li YF, Tan J, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett, 2014, 348(1-2): 77-87.
9.	Sanguinete MMM, Oliveira PH, Martins-Filho A, et al. Serum IL-6 and IL-8 correlate with prognostic factors in ovarian cancer. Immunol Invest, 2017, 46(7): 677-688.
10.	杨青, 张香梅, 翁晨刚, 等. 敲低 MDA-MB-231 中 IL-8 的表达影响其增殖和 EMT 过程的相关研究. 第十三届全国免疫学学术大会, 上海, 2018.
11.	朱江, 赵春英, 顾伟, 等. 乳腺癌白介素 8 基因表达及其临床意义. 肿瘤, 2005, 25(4): 386-389.
12.	Bendrik C, Dabrosin C. Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo. J Immunol, 2009, 182(1): 371-378.
13.	Cho EY, Chang MH, Choi YL, et al. Potential candidate biomarkers for heterogeneity in triple-negative breast cancer (TNBC). Cancer Chemother Pharmacol, 2011, 68(3): 753-761.
14.	Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer, 2010.
15.	Lakhani SR, Ellis IO, Schnitt SJ, et al. WHO classification of tumours of the breast. Lyon: IABC Press, 2012: 13-15.
16.	Yerushalmi R, Woods R, Ravdin PM, et al. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol, 2010, 11(2): 174-183.
17.	肖培, 叶英楠, 宁俊雅, 等. IL-8 诱导的肿瘤相关巨噬细胞对肝细胞肝癌侵袭转移的影响. 中国肿瘤临床, 2018, 45(2): 55-62.
18.	杨青, 张香梅, 翁晨刚, 等. IL-8 及其受体在肿瘤进展与治疗中的研究进展. 肿瘤防治研究, 2019, 46(1): 81-84.
19.	杨青, 张香梅, 何明, 等. 下调 IL-8 表达抑制食管鳞状细胞癌 KYSE170 细胞的迁移能力及其相关机制. 中国肿瘤生物治疗杂志, 2018, 25(8): 785-790.
20.	方复, 毛华辉, 卢国春, 等. IL-8 在胃癌组织上皮间质转化过程中表达增强. 基础医学与临床, 2019, 39(10): 1444-1448.
21.	Shibakura M, Niiya K, Kiguchi T, et al. Induction of IL-8 and monoclyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. International journal of cancer, 2003, 103(3): 380-386.
22.	Tobin RP, Jordan KR, Kapoor P, et al. IL-6 and IL-8 are linked with myeloid-derived suppressor cell accumulation and correlate with poor clinical outcomes in melanoma patients. Front Oncol, 2019, 9: 1223.
23.	Duffy MJ, Harbeck N, Nap M, et al. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer, 2017, 75: 284-298.
24.	谭敏华, 雷伟华, 胡志雄, 等. 乳腺癌组织中 p53 和 Ki67 蛋白的表达及意义. 广东医学, 2017, 38(S2): 101-104.
25.	Lin Y, Huang R, Chen L, et al. Identification of interleukin-8 as estrogen receptor-regulated factor involved in breast cancer invasion and angiogenesis by protein arrays. Int J Cancer, 2004, 109(4): 507-515.
26.	王若珺, 初明, 岑羽捷, 等. 新生淋巴管与乳腺癌淋巴管转移相关性的研究进展. 生理科学进展, 2014, 45(1): 49-54.
27.	Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6): 1471-1474.
28.	黄琳, 滕美君, 徐竟男, 等. HIF-1α、ALDH1 和 Hedgehog 信号通路协同促进三阴性乳腺癌中癌症干细胞活化的相关性研究. 中国免疫学杂志, 2017, 33(5): 697-701.
29.	Sharma B, Singh S, Varney ML, et al. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin Ther Targets, 2010, 14(4): 435-442.
30.	Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, et al. Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treat Rev, 2017, 60: 24-31.
31.	David JM, Dominguez C, Hamilton DH, et al. The IL-8/IL-8R axis: a double agent in tumor immune resistance. Vaccines (Basel), 2016, 4(3): 22.
32.	Dey N, De P, Leyland-Jones B. PI3K-AKT-mTOR inhibitors in breast cancers: from tumor cell signaling to clinical trials. Pharmacol Ther, 2017, 175: 91-106.
33.	Balacescu O, Balacescu L, Virtic O, et al. Blood genome-wide transcriptional profiles of her2 negative breast cancers patients. Mediators Inflamm, 2016, 2016: 3239167.
34.	Fu XT, Dai Z, Song K, et al. Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway. Int J Oncol, 2015, 46(2): 587-596.
35.	黄佳欢, 陈俊青, 杨紫烟, 等. PI3K/AKT/mTOR 信号通路在三阴性乳腺癌中的作用及靶向治疗研究进展. 肿瘤学杂志, 2020, 26(9): 784-790.
36.	景文江, 赵新汉, 马武, 等. mTOR 蛋白和 Beclin1 蛋白在三阴性乳腺癌组织中的表达及临床意义. 现代肿瘤医学, 2019, 27(10): 1745-1749.
37.	Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.

1. 陈万青, 郑荣寿. 中国女性乳腺癌发病死亡和生存状况. 中国肿瘤临床, 2015, 42(13): 668-674.
2. Clinton SK, Giovannucci EL, Hursting SD. The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions. J Nutr, 2020, 150(4): 663-671.
3. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med, 2010, 363(20): 1938-1948.
4. 牟成金, 潘武, 李娟, 等. 干扰 IL-8 表达对乳腺癌细胞侵袭、迁移能力的影响. 免疫学杂志, 2018, 34(9): 765-771.
5. Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res, 2008, 14(21): 6735-6741.
6. 柴瑛. 骨肉瘤患者白细胞介素 8 表达及其对骨肉瘤细胞增殖、迁移的作用和机制. 中国老年学杂志, 2018, 38(10): 2475-2476.
7. 罗先荣, 彭家清, 熊燕, 等. IL-8 通过下调 miR-199a-3p 对肾癌细胞迁移、侵袭及上皮-间质转化的影响. 免疫学杂志, 2019, 35(12): 1037-1042.
8. Cheng XS, Li YF, Tan J, et al. CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett, 2014, 348(1-2): 77-87.
9. Sanguinete MMM, Oliveira PH, Martins-Filho A, et al. Serum IL-6 and IL-8 correlate with prognostic factors in ovarian cancer. Immunol Invest, 2017, 46(7): 677-688.
10. 杨青, 张香梅, 翁晨刚, 等. 敲低 MDA-MB-231 中 IL-8 的表达影响其增殖和 EMT 过程的相关研究. 第十三届全国免疫学学术大会, 上海, 2018.
11. 朱江, 赵春英, 顾伟, 等. 乳腺癌白介素 8 基因表达及其临床意义. 肿瘤, 2005, 25(4): 386-389.
12. Bendrik C, Dabrosin C. Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo. J Immunol, 2009, 182(1): 371-378.
13. Cho EY, Chang MH, Choi YL, et al. Potential candidate biomarkers for heterogeneity in triple-negative breast cancer (TNBC). Cancer Chemother Pharmacol, 2011, 68(3): 753-761.
14. Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer, 2010.
15. Lakhani SR, Ellis IO, Schnitt SJ, et al. WHO classification of tumours of the breast. Lyon: IABC Press, 2012: 13-15.
16. Yerushalmi R, Woods R, Ravdin PM, et al. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol, 2010, 11(2): 174-183.
17. 肖培, 叶英楠, 宁俊雅, 等. IL-8 诱导的肿瘤相关巨噬细胞对肝细胞肝癌侵袭转移的影响. 中国肿瘤临床, 2018, 45(2): 55-62.
18. 杨青, 张香梅, 翁晨刚, 等. IL-8 及其受体在肿瘤进展与治疗中的研究进展. 肿瘤防治研究, 2019, 46(1): 81-84.
19. 杨青, 张香梅, 何明, 等. 下调 IL-8 表达抑制食管鳞状细胞癌 KYSE170 细胞的迁移能力及其相关机制. 中国肿瘤生物治疗杂志, 2018, 25(8): 785-790.
20. 方复, 毛华辉, 卢国春, 等. IL-8 在胃癌组织上皮间质转化过程中表达增强. 基础医学与临床, 2019, 39(10): 1444-1448.
21. Shibakura M, Niiya K, Kiguchi T, et al. Induction of IL-8 and monoclyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. International journal of cancer, 2003, 103(3): 380-386.
22. Tobin RP, Jordan KR, Kapoor P, et al. IL-6 and IL-8 are linked with myeloid-derived suppressor cell accumulation and correlate with poor clinical outcomes in melanoma patients. Front Oncol, 2019, 9: 1223.
23. Duffy MJ, Harbeck N, Nap M, et al. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer, 2017, 75: 284-298.
24. 谭敏华, 雷伟华, 胡志雄, 等. 乳腺癌组织中 p53 和 Ki67 蛋白的表达及意义. 广东医学, 2017, 38(S2): 101-104.
25. Lin Y, Huang R, Chen L, et al. Identification of interleukin-8 as estrogen receptor-regulated factor involved in breast cancer invasion and angiogenesis by protein arrays. Int J Cancer, 2004, 109(4): 507-515.
26. 王若珺, 初明, 岑羽捷, 等. 新生淋巴管与乳腺癌淋巴管转移相关性的研究进展. 生理科学进展, 2014, 45(1): 49-54.
27. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 2010, 17(6): 1471-1474.
28. 黄琳, 滕美君, 徐竟男, 等. HIF-1α、ALDH1 和 Hedgehog 信号通路协同促进三阴性乳腺癌中癌症干细胞活化的相关性研究. 中国免疫学杂志, 2017, 33(5): 697-701.
29. Sharma B, Singh S, Varney ML, et al. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin Ther Targets, 2010, 14(4): 435-442.
30. Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, et al. Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treat Rev, 2017, 60: 24-31.
31. David JM, Dominguez C, Hamilton DH, et al. The IL-8/IL-8R axis: a double agent in tumor immune resistance. Vaccines (Basel), 2016, 4(3): 22.
32. Dey N, De P, Leyland-Jones B. PI3K-AKT-mTOR inhibitors in breast cancers: from tumor cell signaling to clinical trials. Pharmacol Ther, 2017, 175: 91-106.
33. Balacescu O, Balacescu L, Virtic O, et al. Blood genome-wide transcriptional profiles of her2 negative breast cancers patients. Mediators Inflamm, 2016, 2016: 3239167.
34. Fu XT, Dai Z, Song K, et al. Macrophage-secreted IL-8 induces epithelial-mesenchymal transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway. Int J Oncol, 2015, 46(2): 587-596.
35. 黄佳欢, 陈俊青, 杨紫烟, 等. PI3K/AKT/mTOR 信号通路在三阴性乳腺癌中的作用及靶向治疗研究进展. 肿瘤学杂志, 2020, 26(9): 784-790.
36. 景文江, 赵新汉, 马武, 等. mTOR 蛋白和 Beclin1 蛋白在三阴性乳腺癌组织中的表达及临床意义. 现代肿瘤医学, 2019, 27(10): 1745-1749.
37. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 2011, 121(7): 2750-2767.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Differential expression of IL-8 in triple negative breast cancer and its clinical significance

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content