The expression levels and significance of serum microRNA-21 and microRNA-155 from patients and rats with pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIN Xianchao , WEN Shi , PAN Yu , TENG Tianhong , CHEN Fei ,  HUANG Heguang

Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China;

Corresponding author：

HUANG Heguang, Email: heguanghuang2@163.com

Keywords：

pancreatic cancer; diagnosis; serum biomarker; microRNA-21; microRNA-155

DOI：

10.7507/1007-9424.201804006

Video：

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Objectives To evaluate the expression levels of serum microRNA-21 (miRNA-21) and microRNA-155 (miRNA-155) from patients and rats with pancreatic cancer, and to explore its value in the diagnosis of pancreatic cancer. Methods The clinical materials and the serum samples from 18 patients with pancreatic cancer (pancreatic cancer group) and 12 patients with benign pancreatic disease (benign pancreatic disease group) admitted to Fujian Medical University Union Hospital between January 2016 and December 2016 were collected prospectively. The real-time fluorescent quantitative PCR was performed to detect the levels of serum miRNA-21 and miRNA-155. 7, 12-dimethylbenz (a) anthracene (DMBA)-induced pancreatic cancer rat models (n=20) and the models of the blank control group (sham operation, n=10) were established and the serum samples from the pancreatic cancer group and the blank control group were measured by the real-time fluorescent quantitative PCR, to detect the levels of miRNA-21 and miRNA-155. Results The median expression levels of serum miRNA-21 and miRNA-155 were 1.99 (1.43–5.30) and 7.06 (4.98–21.48) in the pancreatic cancer group, as well as 1.28 (0.58–2.01) and 2.20 (1.76–3.02) in the benign pancreatic disease group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the pancreatic cancer group (Z=–2.621,P=0.009; Z=–3.430,P=0.001). In animal studies, the rat models of pancreatic cancer were successfully established and 11 rats with pancreatic cancer were acquired, as well as 9 rats in the blank control group were acquired. The median expression levels of serum miRNA-21 and miRNA-155 were 2.12 (1.33–2.72) and 16.45 (7.18–25.40) in the rat pancreatic cancer group, as well as 1.00 (0.45–1.60) and 1.49 (1.25–1.97) in the blank control group. The expression levels of serum miRNA-21 and miRNA-155 were significantly higher in the rat pancreatic cancer group (Z=–2.621,P=0.009; Z=–3.609,P<0.001). For distinguishing pancreatic cancer from benign diseases, the best cutoff value of serum miRNA-21 level was 4.21 and the sensitivity and specificity were 75.0% and 61.1% respectively; the best cutoff value of serum miRNA-155 level was 4.67 and the sensitivity and specificity both were 83.3%. Conclusions The serum miRNA-21and miRNA-155 levels are elevated both in patients and rats with pancreatic cancer. Detection of serum miRNA-155 will be helpful to some extent to distinguish pancreatic cancer from benign diseases.

Citation： LIN Xianchao, WEN Shi, PAN Yu, TENG Tianhong, CHEN Fei, HUANG Heguang. The expression levels and significance of serum microRNA-21 and microRNA-155 from patients and rats with pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(10): 1171-1175. doi: 10.7507/1007-9424.201804006 Copy

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2.	Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
3.	姚汝铖, 郑军, 邢荣春. 微小RNA在胰腺癌中的研究进展. 中国普外基础与临床杂志, 2012, 19(8): 911-915.
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6.	Qu K, Zhang X, Lin T, et al. Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation. Sci Rep, 2017, 7(1): 1692.
7.	Duell EJ, Lujan-Barroso L, Sala N, et al. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. Int J Cancer, 2017, 141(5): 905-915.
8.	Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc, 2008, 3(6): 1101-1108.
9.	de la Santa LG, Retortillo JA, Miguel AC, et al. Radiology of pancreatic neoplasms: an update. World J Gastrointest Oncol, 2014, 6(9): 330-343.
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11.	Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol, 2012, 3(2): 105-119.
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13.	Duffy MJ, Sturgeon C, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol, 2010, 21(3): 441-447.
14.	Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol, 2007, 33(3): 266-270.
15.	Kawaguchi T, Komatsu S, Ichikawa D, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. Br J Cancer, 2013, 108(2): 361-369.
16.	Schultz NA, Dehlendorff C, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA, 2014, 311(4): 392-404.
17.	Meng QC, Qiu WW, Wen ZQ, et al. Novel blood-based microRNA biomarkers for diagnosis of pancreatic cancer: a meta-analysis. Tumori, 2015, 101(2): 199-205.
18.	Liu R, Chen X, Du Y, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem, 2012, 58(3): 610-618.
19.	Frampton AE, Giovannetti E, Jamieson NB, et al. A microRNA meta-signature for pancreatic ductal adenocarcinoma. Expert Rev Mol Diagn, 2014, 14(3): 267-271.
20.	Abue M, Yokoyama M, Shibuya R, et al. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol, 2015, 46(2): 539-547.
21.	du Rieu MC, Torrisani J, Selves J, et al. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem, 2010, 56(4): 603-612.
22.	Wang J, Chen J, Chang P, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila), 2009, 2(9): 807-813.
23.	Cote GA, Gore AJ, McElyea SD, et al. A pilot study to develop a diagnostic test for pancreatic ductal adenocarcinoma based on differential expression of select miRNA in plasma and bile. Am J Gastroenterol, 2014, 109(12): 1942-1952.
24.	Sempere LF, Preis M, Yezefski T, et al. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors. Clin Cancer Res, 2010, 16(16): 4246-4255.
25.	Ryu JK, Hong SM, Karikari CA, et al. Aberrant microRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatology, 2010, 10(1): 66-73.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
2. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
3. 姚汝铖, 郑军, 邢荣春. 微小RNA在胰腺癌中的研究进展. 中国普外基础与临床杂志, 2012, 19(8): 911-915.
4. Hernandez YG, Lucas AL. MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions. World J Gastrointest Oncol, 2016, 8(1): 18-29.
5. Xu J, Cao Z, Liu W, et al. Plasma miRNAs effectively distinguish patients with pancreatic cancer from controls: a multicenter study. Ann Surg, 2016, 263(6): 1173-1179.
6. Qu K, Zhang X, Lin T, et al. Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation. Sci Rep, 2017, 7(1): 1692.
7. Duell EJ, Lujan-Barroso L, Sala N, et al. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. Int J Cancer, 2017, 141(5): 905-915.
8. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc, 2008, 3(6): 1101-1108.
9. de la Santa LG, Retortillo JA, Miguel AC, et al. Radiology of pancreatic neoplasms: an update. World J Gastrointest Oncol, 2014, 6(9): 330-343.
10. Pietryga JA, Morgan DE. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol, 2015, 6(4): 343-357.
11. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol, 2012, 3(2): 105-119.
12. Decker GA, Batheja MJ, Collins JM, et al. Risk factors for pancreatic adenocarcinoma and prospects for screening. Gastroenterol Hepatol (N Y), 2010, 6(4): 246-254.
13. Duffy MJ, Sturgeon C, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol, 2010, 21(3): 441-447.
14. Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol, 2007, 33(3): 266-270.
15. Kawaguchi T, Komatsu S, Ichikawa D, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. Br J Cancer, 2013, 108(2): 361-369.
16. Schultz NA, Dehlendorff C, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA, 2014, 311(4): 392-404.
17. Meng QC, Qiu WW, Wen ZQ, et al. Novel blood-based microRNA biomarkers for diagnosis of pancreatic cancer: a meta-analysis. Tumori, 2015, 101(2): 199-205.
18. Liu R, Chen X, Du Y, et al. Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer. Clin Chem, 2012, 58(3): 610-618.
19. Frampton AE, Giovannetti E, Jamieson NB, et al. A microRNA meta-signature for pancreatic ductal adenocarcinoma. Expert Rev Mol Diagn, 2014, 14(3): 267-271.
20. Abue M, Yokoyama M, Shibuya R, et al. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol, 2015, 46(2): 539-547.
21. du Rieu MC, Torrisani J, Selves J, et al. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem, 2010, 56(4): 603-612.
22. Wang J, Chen J, Chang P, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila), 2009, 2(9): 807-813.
23. Cote GA, Gore AJ, McElyea SD, et al. A pilot study to develop a diagnostic test for pancreatic ductal adenocarcinoma based on differential expression of select miRNA in plasma and bile. Am J Gastroenterol, 2014, 109(12): 1942-1952.
24. Sempere LF, Preis M, Yezefski T, et al. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors. Clin Cancer Res, 2010, 16(16): 4246-4255.
25. Ryu JK, Hong SM, Karikari CA, et al. Aberrant microRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatology, 2010, 10(1): 66-73.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expression levels and significance of serum microRNA-21 and microRNA-155 from patients and rats with pancreatic cancer

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