Expression and clinical significance of circ-MFN2 in pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 LI Siqiao , CHANG Qingtan , LIU Haichao , LIU Shaopeng

Department of Hepatobiliary Surgery, Luoyang Central Hospital, Affiliated to Zhengzhou University, Luoyang, Henan 471000, P. R. China;

Corresponding author：

LI Siqiao, Email: 316245839@qq.com

Keywords：

pancreatic cancer; circular mitochondrial fusin 2; prognosis

DOI：

10.7507/1007-9424.202009025

Video：

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Objective To investigate the expression of circular RNA mitochondrial fusin 2 (circ-MFN2) in pancreatic cancer and analyze its correlation with clinicopathological features and prognosis.Methods The expressions of circ-MFN2 miRNA in 55 cases of pancreatic cancer tissues and serum were detected by qRT-PCR, and analyzed the correlation between circ-MFN2 and clinicopathological factors of pancreatic cancer and prognosis. The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA in the diagnosis of pancreatic cancer were statistically analyzed. ROC curve was used to analyze its efficacy as a biomarker for early diagnosis of pancreatic cancer.Results Compared with paracancerous tissues of pancreatic cancer and serum of healthy control group, circ-MFN2 miRNA was highly expressed in pancreatic cancer tissues and serum, and the difference were all statistically significant (all P<0.05). Chi square test showed that the expression of circ-MFN2 miRNA in pancreatic cancer tissues was not related to age, gender, tumor size, pathological type, and tumor site (P>0.05), but was significantly related to CA19-9 level, TNM stage, tumor differentiation and lymph node metastasis (P<0.05). The sensitivity, specificity and accuracy of expression of circ-MFN2 miRNA for pancreatic cancer were 72.7%, 70.9% and 83.6% respectively, which were all higher than that of CA19-9 (54.5%, 50.9% and 52.7%, P<0.05). Kaplan-Meier analysis showed that the median survival time of pancreatic cancer patients with high expression of circ-MFN2 miRNA was significantly shorter than that of patients with low expression (9.1 months vs 22.3 months, P<0.05). The area under ROC curve of circ-MFN2 miRNA as a serum biomarker for the diagnosis of pancreatic cancer was 0.861 [95%CI (0.775, 1.157), P=0.000]. Cox multivariate analysis showed that the expression of cirC-MFN2 miRNA and lymph node metastasis were independent risk factors for the prognosis of pancreatic cancer patients.Conclusions Circ-MFN2 miRNA is highly expressed in pancreatic cancer tissues, and it is related to the clinical characteristics and prognosis of patients. It is expected to be a new molecular marker to predict the prognosis of pancreatic cancer.

Citation： LI Siqiao, CHANG Qingtan, LIU Haichao, LIU Shaopeng. Expression and clinical significance of circ-MFN2 in pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(6): 762-767. doi: 10.7507/1007-9424.202009025 Copy

1.	吕少诚, 贺强, 郎韧, 等. 外科手术在伴有门静脉系统侵犯的胰腺癌治疗中的临床价值. 中华胰腺病杂志, 2020, 20(4): 254-258.
2.	张太平, 刘悦泽, 曹喆. 新辅助治疗背景下胰腺癌扩大切除术的应用价值. 中华外科杂志, 2020, 58(7): 481-485.
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5.	Bunch H. Gene regulation of mammalian long non-coding RNA. Mol Genet Genomics, 2018, 293(1): 1-15.
6.	Li X, Li C, Liu Z, et al. Circular RNA circ-FoxO3 inhibits myoblast cells differentiation. Cells, 2019, 8(6): 616.
7.	高哈尔, 刘芬, 马峻岭, 等. 血清环状 RNA 表达与胃癌关系的探索性研究. 中华流行病学杂志, 2019, 40(12): 1527-1532.
8.	赵静, 杨兴武, 李京涛, 等. 基于高通量测序的肝癌 circRNA-miRNA-mRNA 调控网络构建及功能富集分析. 临床肝胆病杂志, 2019, 35(8): 1740-1744.
9.	李丽仙, 何永鹏, 陈霞, 等. 环状 RNAs 在乳腺癌中的研究进展. 中华乳腺病杂志(电子版), 2020, 14(3): 173-179.
10.	Roitinger E, Hofer M, Köcher T, et al. Quantitative phosphoproteomics of the ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia-mutated and rad3-related (ATR) dependent DNA damage response in Arabidopsis thaliana. Mol Cell Proteomics, 2015, 14(3): 556-571.
11.	Wang L, Long H, Zheng Q, et al. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer, 2019, 18(1): 119.
12.	Li GF, Li L, Yao ZQ, et al. Hsa_circ_0007534/miR-761/ZIC5 regulatory loop modulates the proliferation and migration of glioma cells. Biochem Biophys Res Commun, 2018, 499(4): 765-771.
13.	刘彦, 周超, 杨永学. ciRS-7/miR-7 轴调控肿瘤生长转移的研究进展. 中国普通外科杂志, 2015, 24(7): 1027-1031.
14.	王婷婷, 韩影, 高芳芳, 等. 环状RNA circ-SOD2 对肠上皮屏障和溃疡性结肠炎的作用. 北京大学学报(医学版), 2019, 51(5): 805-812.
15.	Du WW, Yang W, Li X, et al. A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy. Oncogene, 2018, 37(44): 5829-5842.
16.	杨帆. 环状 RNAcirc-MFN2 在胰腺癌中作为新型诊断生物标志物及其通过 miR-133a-3p/SLC39A4 调控胰腺癌发生发展的机制研究. 中国医科大学, 2018.
17.	曹锋, 李非. 腹腔镜技术在胰腺癌术中再分期的应用. 中华消化外科杂志, 2020, 19(5): 505-510.
18.	雷鹏, 唐超峰, 卜稳平, 等. 溶质载体转运蛋白 22A3 基因 rs7758229 多态性与胰腺癌预后的关系. 中华实验外科杂志, 2020, 37(1): 22-24.
19.	言方荣, 朱惠红, 蒋丽芸, 等. 生物等效性评价早期停止条件研究. 中国卫生统计, 2017, 34(5): 825-828, 831.
20.	Qian L, Li Q, Baryeh K, et al. Biosensors for early diagnosis of pancreatic cancer: a review. Transl Res, 2019, 213: 67-89.
21.	Sabater L, Muñoz E, Roselló S, et al. Borderline resectable pancreatic cancer. Challenges and controversies. Cancer Treat Rev, 2018, 68: 124-135.
22.	Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta, 2015, 444: 132-136.
23.	张鹤达, 李伟, 钟山亮, 等. GEO 数据库分析环状 RNA 在乳腺癌组织中的表达. 中国肿瘤外科杂志, 2019, 11(6): 401-405.
24.	刘喻萍, 张莉, 刘诗意, 等. circRNA 生物学特性及其在肿瘤中的研究进展. 武汉大学学报(医学版), 2020, 41(3): 438-443.
25.	Li D, Yang Y, Li ZQ, et al. Circular RNAs: from biogenesis and function to diseases. Chin Med J (Engl), 2019, 132(20): 2457-2464.
26.	Xu X, Zhang J, Tian Y, et al. CircRNA inhibits DNA damage repair by interacting with host gen. Mol Cancer, 2020, 19(1): 128.
27.	刘乘熙, 王奕智, 郭俊超. 环状 RNA 的研究进展及胰腺癌中的应用. 中华实验外科杂志, 2020, 37(1): 5-11.

1. 吕少诚, 贺强, 郎韧, 等. 外科手术在伴有门静脉系统侵犯的胰腺癌治疗中的临床价值. 中华胰腺病杂志, 2020, 20(4): 254-258.
2. 张太平, 刘悦泽, 曹喆. 新辅助治疗背景下胰腺癌扩大切除术的应用价值. 中华外科杂志, 2020, 58(7): 481-485.
3. Suzuki F, Fujiwara Y, Hamura R, et al. Combination of distance from superior mesenteric artery and serum CA19-9 as a novel prediction of local recurrence in patients with pancreatic cancer following resection. Anticancer Res, 2019, 39(3): 1469-1478.
4. Li R, Jiang J, Shi H, et al. CircRNA: a rising star in gastric cancer. Cell Mol Life Sci, 2020, 77(9): 1661-1680.
5. Bunch H. Gene regulation of mammalian long non-coding RNA. Mol Genet Genomics, 2018, 293(1): 1-15.
6. Li X, Li C, Liu Z, et al. Circular RNA circ-FoxO3 inhibits myoblast cells differentiation. Cells, 2019, 8(6): 616.
7. 高哈尔, 刘芬, 马峻岭, 等. 血清环状 RNA 表达与胃癌关系的探索性研究. 中华流行病学杂志, 2019, 40(12): 1527-1532.
8. 赵静, 杨兴武, 李京涛, 等. 基于高通量测序的肝癌 circRNA-miRNA-mRNA 调控网络构建及功能富集分析. 临床肝胆病杂志, 2019, 35(8): 1740-1744.
9. 李丽仙, 何永鹏, 陈霞, 等. 环状 RNAs 在乳腺癌中的研究进展. 中华乳腺病杂志(电子版), 2020, 14(3): 173-179.
10. Roitinger E, Hofer M, Köcher T, et al. Quantitative phosphoproteomics of the ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia-mutated and rad3-related (ATR) dependent DNA damage response in Arabidopsis thaliana. Mol Cell Proteomics, 2015, 14(3): 556-571.
11. Wang L, Long H, Zheng Q, et al. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer, 2019, 18(1): 119.
12. Li GF, Li L, Yao ZQ, et al. Hsa_circ_0007534/miR-761/ZIC5 regulatory loop modulates the proliferation and migration of glioma cells. Biochem Biophys Res Commun, 2018, 499(4): 765-771.
13. 刘彦, 周超, 杨永学. ciRS-7/miR-7 轴调控肿瘤生长转移的研究进展. 中国普通外科杂志, 2015, 24(7): 1027-1031.
14. 王婷婷, 韩影, 高芳芳, 等. 环状RNA circ-SOD2 对肠上皮屏障和溃疡性结肠炎的作用. 北京大学学报(医学版), 2019, 51(5): 805-812.
15. Du WW, Yang W, Li X, et al. A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy. Oncogene, 2018, 37(44): 5829-5842.
16. 杨帆. 环状 RNAcirc-MFN2 在胰腺癌中作为新型诊断生物标志物及其通过 miR-133a-3p/SLC39A4 调控胰腺癌发生发展的机制研究. 中国医科大学, 2018.
17. 曹锋, 李非. 腹腔镜技术在胰腺癌术中再分期的应用. 中华消化外科杂志, 2020, 19(5): 505-510.
18. 雷鹏, 唐超峰, 卜稳平, 等. 溶质载体转运蛋白 22A3 基因 rs7758229 多态性与胰腺癌预后的关系. 中华实验外科杂志, 2020, 37(1): 22-24.
19. 言方荣, 朱惠红, 蒋丽芸, 等. 生物等效性评价早期停止条件研究. 中国卫生统计, 2017, 34(5): 825-828, 831.
20. Qian L, Li Q, Baryeh K, et al. Biosensors for early diagnosis of pancreatic cancer: a review. Transl Res, 2019, 213: 67-89.
21. Sabater L, Muñoz E, Roselló S, et al. Borderline resectable pancreatic cancer. Challenges and controversies. Cancer Treat Rev, 2018, 68: 124-135.
22. Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta, 2015, 444: 132-136.
23. 张鹤达, 李伟, 钟山亮, 等. GEO 数据库分析环状 RNA 在乳腺癌组织中的表达. 中国肿瘤外科杂志, 2019, 11(6): 401-405.
24. 刘喻萍, 张莉, 刘诗意, 等. circRNA 生物学特性及其在肿瘤中的研究进展. 武汉大学学报(医学版), 2020, 41(3): 438-443.
25. Li D, Yang Y, Li ZQ, et al. Circular RNAs: from biogenesis and function to diseases. Chin Med J (Engl), 2019, 132(20): 2457-2464.
26. Xu X, Zhang J, Tian Y, et al. CircRNA inhibits DNA damage repair by interacting with host gen. Mol Cancer, 2020, 19(1): 128.
27. 刘乘熙, 王奕智, 郭俊超. 环状 RNA 的研究进展及胰腺癌中的应用. 中华实验外科杂志, 2020, 37(1): 5-11.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and clinical significance of circ-MFN2 in pancreatic cancer

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