The relationship between Epstein-Barr virus infection and the expressions of serum KISS-1 and MMP2 in patients with colon cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YU Fei , WANG Tao , SHI Zhen , SONG Jian , SHAN Yazhou

Department of Gastrointestinal Surgery, Huanghe Sanmenxia Hospital, Sanmenxia, Henan 472000, P. R. China;

Corresponding author：

YU Fei, Email: yjh75hua@163.com

Keywords：

colon cancer; Epstein-Barr virus; kisspeptin-1; matrix metalloproteinase 2

DOI：

10.7507/1007-9424.202105035

Video：

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Objective To explore the relationship between Epstein-Barr virus (EBV) infection with serum human kissin-1 (KISS-1) and matrix metalloproteinase 2 (MMP2) levels and prognosis in patients with colon cancer. Methods A total of 86 colon cancer patients who were hospitalized in our hospital from April 2015 to April 2016 were selected as the colon cancer group; in the same period, 84 cases of physical examination person in our hospital were selected as the control group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to test colon cancer patients for EBV DNA, and divided the patients into EBV DNA negative group and EBV DNA positive group according to the test results. Enzyme-linked immunosorbent (ELISA) method was used to detect serum KISS-1 and MMP2 levels. Pearson method was used to analyze the correlation between serum KISS-1 and MMP2 levels in patients with colon cancer infected with EBV. The survival curve was drawn by Kaplan-Meier method, and the relationship between EBV infection and prognosis of colon cancer patients was analyzed by log-rank test. Multivariate Cox regression analysis were used to analyze the factors affecting the prognosis of colon cancer patients. Results Compared with the control group, the positive rate of EBV DNA in the colon cancer group was higher (χ²=21.854, P<0.001). The EBV DNA positive rate of patients with lymph node metastasis, TNM stage Ⅲ–Ⅳ, tumor low differentiation and tumor infiltration T3–T4 was higher than those without lymph node metastasis, TNM stage Ⅰ–Ⅱ, tumor high/medium differentiation and tumor infiltration T1–T2 (P<0.05). Compared with the EBV DNA negative group, the serum KISS-1 level of the EBV DNA positive group decreased, and the MMP2 level increased (P<0.001). There was a negative correlation between serum KISS-1 and MMP2 levels in colon cancer patients with EBV infection (r=–0.510, P<0.001). The 5-year survival rates of colon cancer patients in the EBV DNA-negative group and the EBV DNA-positive group were 52.94% (27/51) and 14.29% (5/35), respectively, the difference between the two groups was statistically significant (χ²=13.274, P<0.001). EBV infection, MMP2 high expression, and lymph node metastasis were independent risk factors affecting the prognosis of colon cancer patients (P<0.05), and KISS-1 low expression was a protective factor affecting the prognosis of colon cancer patients (P<0.05). Conclusions EBV infection is closely related to the progression and prognosis of colon cancer. The down-regulation of KISS-1 and the up-regulation of MMP2 may be related to EBV infection.

Citation： YU Fei, WANG Tao, SHI Zhen, SONG Jian, SHAN Yazhou. The relationship between Epstein-Barr virus infection and the expressions of serum KISS-1 and MMP2 in patients with colon cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(2): 226-231. doi: 10.7507/1007-9424.202105035 Copy

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2.	赵帅华, 董卫红, 杨敬, 等. ABHD5过表达对结肠癌细胞侵袭、迁移及AMPK/mTOR通路的影响. 中国普外基础与临床杂志, 2021, 28(7): 850-855.
3.	勾静娴, 姜相君, 曲海霞, 等. 补体C1q/肿瘤坏死因子相关蛋白6在结肠癌中的表达. 胃肠病学和肝病学杂志, 2019, 28(3): 313-316.
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5.	Huang YH, Zhang CZ, Huang QS, et al. Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma. J Hepatol, 2021, 74(4): 838-849.
6.	卫美蓉, 王笑峰, 罗兵. lncRNA HOTAIR和H19 SNPs与胃癌及EB病毒相关胃癌遗传易感性的关系. 中国病理生理杂志, 2020, 36(11): 2030-2036.
7.	Wang XQ, Fang PF, Zhang C, et al. Low KISS1 expression predicts poor prognosis for patients with colorectal cancer: A meta-analysis. Clin Exp Pharmacol Physiol, 2019, 46(7): 625-634.
8.	康清杰, 向征. 胶质瘤相关癌基因同源蛋白2促进结肠癌细胞系SW620的上皮-间质转化. 中国癌症杂志, 2020, 30(4): 254-260.
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10.	杜兴冉, 徐喨, 蔡洁, 等. EB病毒相关噬血细胞性淋巴组织细胞增生症的临床特征及预后危险因素分析. 中华临床感染病杂志, 2014, 7(2): 111-115.
11.	马晓朋. 儿童EB病毒感染相关淋巴增生性疾病的诊治进展. 国际儿科学杂志, 2021, 48(3): 150-154.
12.	Hedström AK, Huang J, Michel A, et al. High levels of Epstein-Barr virus nuclear antigen-1-specific antibodies and infectious mononucleosis act both independently and synergistically to increase multiple sclerosis risk. Front Neurol, 2020, 10: 1368-1382.
13.	彭垒, 贺建华. 微生物感染与食管癌的相关性研究进展. 世界最新医学信息文摘, 2019, 19(6): 66-67, 72.
14.	Ghasemi F, Tessier TM, Gameiro SF, et al. High MHC- Ⅱ expression in Epstein-Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation. Sci Rep, 2020, 10(1): 14786. doi: 10.1038/s41598-020-71775-4.
15.	Osumi H, Kawachi H, Yoshio T, et al. Clinical impact of Epstein-Barr virus status on the incidence of lymph node metastasis in early gastric cancer. Dig Endosc, 2020, 32(3): 316-322.
16.	赵天源, 常延河, 张艳敏, 等. 非小细胞肺癌中KiSS-1、MMP-2和MVD的表达及意义. 临床与实验病理学杂志, 2020, 36(2): 199-202.
17.	Ly T, Harihar S, Welch DR. KISS1 in metastatic cancer research and treatment: potential and paradoxes. Cancer Metastasis Rev, 2020, 39(3): 739-754.
18.	王哲彦, 孟玉秋, 刘春玲, 等. KISS1与KAI1在结肠癌中的表达及临床意义. 临床与病理杂志, 2019, 39(3): 509-514.
19.	赵津, 丁佩剑. 基质金属蛋白酶在结直肠癌中的研究进展. 医疗装备, 2019, 32(10): 193-194.
20.	Wu H, Liu L, Zhu JM. MiR-93-5p inhibited proliferation and metastasis of glioma cells by targeting MMP2. Eur Rev Med Pharmacol Sci, 2019, 23(21): 9517-9524.
21.	Scherer D, Deutelmoser H, Balavarca Y, et al. Polymorphisms in the angiogenesis-related genes EFNB2, MMP2 and JAG1 are associated with survival of colorectal cancer patients. Int J Mol Sci, 2020, 21(15): 5395. doi: 10.3390/ijms21155395.

1. Lai HT, Chiang CT, Tseng WK, et al. GATA6 enhances the stemness of human colon cancer cells by creating a metabolic symbiosis through upregulating LRH-1 expression. Mol Oncol, 2020, 14(6): 1327-1347.
2. 赵帅华, 董卫红, 杨敬, 等. ABHD5过表达对结肠癌细胞侵袭、迁移及AMPK/mTOR通路的影响. 中国普外基础与临床杂志, 2021, 28(7): 850-855.
3. 勾静娴, 姜相君, 曲海霞, 等. 补体C1q/肿瘤坏死因子相关蛋白6在结肠癌中的表达. 胃肠病学和肝病学杂志, 2019, 28(3): 313-316.
4. Caetano BFR, Jorge BAS, Müller-Coan BG, et al. Epstein-Barr virus microRNAs in the pathogenesis of human cancers. Cancer Lett, 2021, 499: 14-23.
5. Huang YH, Zhang CZ, Huang QS, et al. Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma. J Hepatol, 2021, 74(4): 838-849.
6. 卫美蓉, 王笑峰, 罗兵. lncRNA HOTAIR和H19 SNPs与胃癌及EB病毒相关胃癌遗传易感性的关系. 中国病理生理杂志, 2020, 36(11): 2030-2036.
7. Wang XQ, Fang PF, Zhang C, et al. Low KISS1 expression predicts poor prognosis for patients with colorectal cancer: A meta-analysis. Clin Exp Pharmacol Physiol, 2019, 46(7): 625-634.
8. 康清杰, 向征. 胶质瘤相关癌基因同源蛋白2促进结肠癌细胞系SW620的上皮-间质转化. 中国癌症杂志, 2020, 30(4): 254-260.
9. 中华人民共和国国家卫生健康委员会. 中国结直肠癌诊疗规范(2020版). 中华消化外科杂志, 2020, 19(6): 563-588.
10. 杜兴冉, 徐喨, 蔡洁, 等. EB病毒相关噬血细胞性淋巴组织细胞增生症的临床特征及预后危险因素分析. 中华临床感染病杂志, 2014, 7(2): 111-115.
11. 马晓朋. 儿童EB病毒感染相关淋巴增生性疾病的诊治进展. 国际儿科学杂志, 2021, 48(3): 150-154.
12. Hedström AK, Huang J, Michel A, et al. High levels of Epstein-Barr virus nuclear antigen-1-specific antibodies and infectious mononucleosis act both independently and synergistically to increase multiple sclerosis risk. Front Neurol, 2020, 10: 1368-1382.
13. 彭垒, 贺建华. 微生物感染与食管癌的相关性研究进展. 世界最新医学信息文摘, 2019, 19(6): 66-67, 72.
14. Ghasemi F, Tessier TM, Gameiro SF, et al. High MHC- Ⅱ expression in Epstein-Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation. Sci Rep, 2020, 10(1): 14786. doi: 10.1038/s41598-020-71775-4.
15. Osumi H, Kawachi H, Yoshio T, et al. Clinical impact of Epstein-Barr virus status on the incidence of lymph node metastasis in early gastric cancer. Dig Endosc, 2020, 32(3): 316-322.
16. 赵天源, 常延河, 张艳敏, 等. 非小细胞肺癌中KiSS-1、MMP-2和MVD的表达及意义. 临床与实验病理学杂志, 2020, 36(2): 199-202.
17. Ly T, Harihar S, Welch DR. KISS1 in metastatic cancer research and treatment: potential and paradoxes. Cancer Metastasis Rev, 2020, 39(3): 739-754.
18. 王哲彦, 孟玉秋, 刘春玲, 等. KISS1与KAI1在结肠癌中的表达及临床意义. 临床与病理杂志, 2019, 39(3): 509-514.
19. 赵津, 丁佩剑. 基质金属蛋白酶在结直肠癌中的研究进展. 医疗装备, 2019, 32(10): 193-194.
20. Wu H, Liu L, Zhu JM. MiR-93-5p inhibited proliferation and metastasis of glioma cells by targeting MMP2. Eur Rev Med Pharmacol Sci, 2019, 23(21): 9517-9524.
21. Scherer D, Deutelmoser H, Balavarca Y, et al. Polymorphisms in the angiogenesis-related genes EFNB2, MMP2 and JAG1 are associated with survival of colorectal cancer patients. Int J Mol Sci, 2020, 21(15): 5395. doi: 10.3390/ijms21155395.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The relationship between Epstein-Barr virus infection and the expressions of serum KISS-1 and MMP2 in patients with colon cancer

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