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

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.	趙帥華, 董衛紅, 楊敬, 等. ABHD5過表達對結腸癌細胞侵襲、遷移及AMPK/mTOR通路的影響. 中國普外基礎與臨床雜志, 2021, 28(7): 850-855.
3.	勾靜嫻, 姜相君, 曲海霞, 等. 補體C1q/腫瘤壞死因子相關蛋白6在結腸癌中的表達. 胃腸病學和肝病學雜志, 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.	衛美蓉, 王笑峰, 羅兵. lncRNA HOTAIR和H19 SNPs與胃癌及EB病毒相關胃癌遺傳易感性的關系. 中國病理生理雜志, 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. 膠質瘤相關癌基因同源蛋白2促進結腸癌細胞系SW620的上皮-間質轉化. 中國癌癥雜志, 2020, 30(4): 254-260.
9.	中華人民共和國國家衛生健康委員會. 中國結直腸癌診療規范(2020版). 中華消化外科雜志, 2020, 19(6): 563-588.
10.	杜興冉, 徐喨, 蔡潔, 等. EB病毒相關噬血細胞性淋巴組織細胞增生癥的臨床特征及預后危險因素分析. 中華臨床感染病雜志, 2014, 7(2): 111-115.
11.	馬曉朋. 兒童EB病毒感染相關淋巴增生性疾病的診治進展. 國際兒科學雜志, 2021, 48(3): 150-154.
12.	Hedstr?m 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.	彭壘, 賀建華. 微生物感染與食管癌的相關性研究進展. 世界最新醫學信息文摘, 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.	趙天源, 常延河, 張艷敏, 等. 非小細胞肺癌中KiSS-1、MMP-2和MVD的表達及意義. 臨床與實驗病理學雜志, 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.	王哲彥, 孟玉秋, 劉春玲, 等. KISS1與KAI1在結腸癌中的表達及臨床意義. 臨床與病理雜志, 2019, 39(3): 509-514.
19.	趙津, 丁佩劍. 基質金屬蛋白酶在結直腸癌中的研究進展. 醫療裝備, 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. 趙帥華, 董衛紅, 楊敬, 等. ABHD5過表達對結腸癌細胞侵襲、遷移及AMPK/mTOR通路的影響. 中國普外基礎與臨床雜志, 2021, 28(7): 850-855.
3. 勾靜嫻, 姜相君, 曲海霞, 等. 補體C1q/腫瘤壞死因子相關蛋白6在結腸癌中的表達. 胃腸病學和肝病學雜志, 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. 衛美蓉, 王笑峰, 羅兵. lncRNA HOTAIR和H19 SNPs與胃癌及EB病毒相關胃癌遺傳易感性的關系. 中國病理生理雜志, 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. 膠質瘤相關癌基因同源蛋白2促進結腸癌細胞系SW620的上皮-間質轉化. 中國癌癥雜志, 2020, 30(4): 254-260.
9. 中華人民共和國國家衛生健康委員會. 中國結直腸癌診療規范(2020版). 中華消化外科雜志, 2020, 19(6): 563-588.
10. 杜興冉, 徐喨, 蔡潔, 等. EB病毒相關噬血細胞性淋巴組織細胞增生癥的臨床特征及預后危險因素分析. 中華臨床感染病雜志, 2014, 7(2): 111-115.
11. 馬曉朋. 兒童EB病毒感染相關淋巴增生性疾病的診治進展. 國際兒科學雜志, 2021, 48(3): 150-154.
12. Hedstr?m 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. 彭壘, 賀建華. 微生物感染與食管癌的相關性研究進展. 世界最新醫學信息文摘, 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. 趙天源, 常延河, 張艷敏, 等. 非小細胞肺癌中KiSS-1、MMP-2和MVD的表達及意義. 臨床與實驗病理學雜志, 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. 王哲彥, 孟玉秋, 劉春玲, 等. KISS1與KAI1在結腸癌中的表達及臨床意義. 臨床與病理雜志, 2019, 39(3): 509-514.
19. 趙津, 丁佩劍. 基質金屬蛋白酶在結直腸癌中的研究進展. 醫療裝備, 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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