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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2019

01-12-2019 | Pancreatic Cancer | Pancreatic Tumors

MiR-194-5p in Pancreatic Ductal Adenocarcinoma Peritoneal Washings is Associated with Peritoneal Recurrence and Overall Survival in Peritoneal Cytology-Negative Patients

Authors: Hirokazu Kubo, MD, Yukihiko Hiroshima, MD, PhD, Ryutaro Mori, MD, PhD, Yusuke Saigusa, PhD, Takashi Murakami, MD, PhD, Yasuhiro Yabushita, MD, PhD, Yu Sawada, MD, PhD, Yuki Homma, MD, PhD, Takafumi Kumamoto, MD, PhD, Ryusei Matsuyama, MD, PhD, Itaru Endo, MD, PhD

Published in: Annals of Surgical Oncology | Issue 13/2019

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Abstract

Background

Peritoneal dissemination is one of the major recurrence patterns in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with poor prognosis. Here, we assessed the diagnostic potential of microRNA (miRNA) profiles in peritoneal washings for prediction of peritoneal dissemination in PDAC.

Patients and Methods

From January 2016 to July 2017, peritoneal washings were obtained prospectively from 59 patients with PDAC undergoing surgery the Yokohama City University Hospital. MiRNA expression was evaluated by Agilent human miRNA microarray and quantitative reverse-transcription polymerase chain reaction.

Results

Microarray analysis identified upregulated and downregulated miRNAs in peritoneal washings of patients with peritoneal dissemination. We validated four miRNAs (miR-141-3p, miR-194-3p, miR-194-5p, and miR-200c-3p) with high expression in peritoneal washings. The cumulative incidence rate of peritoneal recurrence in peritoneal cytology-negative patients in the miR-194-5p high group was significantly higher than that in the miR-194-5p low group (p = 0.002). Univariate and multivariate analyses revealed that high miR-194-5p was associated with overall survival (OS).

Conclusions

High expression of miR-194-5p in peritoneal washings is associated with peritoneal recurrence and poor OS in patients with peritoneal cytology-negative PDAC.
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Literature
1.
Malvezzi M, Carioli G, Bertuccio P, et al. European cancer mortality predictions for the year 2016 with focus on leukaemias. Ann Oncol. 2016;27(4):725–731.PubMed
2.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: Cancer J Clin. 2017;67(1):7–30.
3.
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921.PubMed
4.
Asagi A, Ohta K, Nasu J, et al. Utility of contrast-enhanced FDG-PET/CT in the clinical management of pancreatic cancer: impact on diagnosis, staging, evaluation of treatment response, and detection of recurrence. Pancreas. 2013;42(1):11–19.PubMed
5.
Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet (London, England). 2016;388(10041):248–257.
6.
Hoshimoto S, Hishinuma S, Shirakawa H, et al. Prognostic significance of intraoperative peritoneal washing cytology for patients with potentially resectable pancreatic ductal adenocarcinoma. Pancreatol. IAP. 2017;17(1):109–114.
7.
Satoi S, Murakami Y, Motoi F, et al. Reappraisal of peritoneal washing cytology in 984 patients with pancreatic ductal adenocarcinoma who underwent margin-negative resection. J Gastrointest Surg. 2015;19(1):6–14 (discussion 14).PubMed
8.
Simojoki M, Santala M, Vuopala S, Kauppila A. The prognostic value of peritoneal cytology in ovarian cancer. Eur J Gynaecol Oncol. 1999;20(5–6):357–360.
9.
Ikoma N, Blum M, Chiang YJ, et al. Yield of staging laparoscopy and lavage cytology for radiologically occult peritoneal carcinomatosis of gastric cancer. Ann Surg Oncol. 2016;23(13):4332–4337.PubMed
10.
Chiu CC, Chen JJ, Su SB, Wang JJ. Value of peritoneal cytology in potentially resectable pancreatic cancer (Br J Surg 2013; 100: 1791–1796). Br J Surg. 2014;101(8):1031.PubMed
11.
Yoshioka R, Saiura A, Koga R, et al. The implications of positive peritoneal lavage cytology in potentially resectable pancreatic cancer. World J Surg. 2012;36(9):2187–2191.PubMed
12.
Yachida S, Fukushima N, Sakamoto M, Matsuno Y, Kosuge T, Hirohashi S. Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer. Br J Surg. 2002;89(5):573–578.PubMed
13.
Aoyama T, Katayama Y, Murakawa M, et al. Clinical implication of peritoneal cytology in the pancreatic cancer patients who underwent curative resection followed by adjuvant gemcitabine or S-1 chemotherapy. Hepato-gastroenterology. 2015;62(137):200–206.PubMed
14.
Cao F, Li J, Li A, Li F. Prognostic significance of positive peritoneal cytology in resectable pancreatic cancer: a systemic review and meta-analysis. Oncotarget. 2017;8(9):15004–15013.PubMedPubMedCentral
15.
Hirabayashi K, Imoto A, Yamada M, et al. Positive intraoperative peritoneal lavage cytology is a negative prognostic factor in pancreatic ductal adenocarcinoma: a retrospective single-center study. Front Oncol. 2015;5:182.PubMedPubMedCentral
16.
Iwagami Y, Eguchi H, Wada H, et al. Implications of peritoneal lavage cytology in resectable left-sided pancreatic cancer. Surg Today. 2015;45(4):444–450.PubMed
17.
Sato K, Mori R, Hiroshima Y, et al. RT-PCR of peritoneal washings predicts peritoneal pancreatic cancer recurrence. J Surg Res. 2018;226:122–130.PubMed
18.
19.
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.PubMed
20.
Song B, Zheng K, Ma H, et al. miR-429 determines poor outcome and inhibits pancreatic ductal adenocarcinoma growth by targeting TBK1. Cell Physiol Biochem. 2015;35(5):1846–1856.PubMed
21.
Tokuhisa M, Ichikawa Y, Kosaka N, et al. Exosomal miRNAs from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer. PLoS One. 2015;10(7):e0130472.PubMedPubMedCentral
22.
Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–196.PubMed
23.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–213.PubMedPubMedCentral
24.
Tsukamoto M, Iinuma H, Yagi T, Matsuda K, Hashiguchi Y. Circulating exosomal microRNA-21 as a biomarker in each tumor stage of colorectal cancer. Oncology. 2017;92(6):360–370.PubMed
25.
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.PubMed
26.
Tempero MA, Arnoletti JP, Behrman S, et al. Pancreatic adenocarcinoma. J Natl Comp Cancer Netw. 2010;8(9):972–1017.
27.
Ariake K, Motoi F, Ohtsuka H, et al. Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention. Surg Today. 2017;47(12):1434–1442.PubMed
28.
Zhang J, Zhao CY, Zhang SH, et al. Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma. Oncol Rep. 2014;31(3):1157–1164.PubMed
29.
Mees ST, Mardin WA, Wendel C, et al. EP300–a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. Int J Cancer. 2010;126(1):114–124.PubMed
30.
Wei R, Ding C, Rodriguez RA, Del Mar Requena Mullor M. The SOX2OT/miR-194-5p axis regulates cell proliferation and mobility of gastric cancer through suppressing epithelial-mesenchymal transition. Oncol Lett. 2018;16(5):6361–6368.PubMedPubMedCentral
31.
Jiang JH, Liu C, Cheng H, et al. Epithelial-mesenchymal transition in pancreatic cancer: Is it a clinically significant factor? Biochim Biophys Acta. 2015;1855(1):43–49.PubMed
32.
33.
Nieto MA, Huang RY, Jackson RA, Thiery JP. EMT: 2016. Cell. 2016;166(1):21–45.PubMed
34.
Scheel C, Weinberg RA. Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Sem Cancer Biol. 2012;22(5-6):396–403.
35.
Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–142.PubMed
36.
Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–2406.PubMed
37.
Roland CL, Yang AD, Katz MH, et al. Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer. Ann Surg Oncol. 2015;22(4):1168–1175.PubMed
38.
Bradley A, Van Der Meer R. Upfront surgery versus neoadjuvant therapy for resectable pancreatic cancer: systematic review and Bayesian network meta-analysis. Sci Rep. 2019;9(1):4354.PubMedPubMedCentral
39.
Bradley A, Van Der Meer R. Neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic cancer: a Markov decision analysis. PLoS One. 2019;14(2):e0212805.PubMedPubMedCentral
40.
Motoi F, Satoi S, Honda G, et al. A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study. J Gastroenterol. 2019;54(2):194–203.PubMed
41.
Vietsch EE, van Eijck CH, Wellstein A. Circulating DNA and micro-RNA in patients with pancreatic cancer. Pancreatic Disorders Ther. 2015;5:2.
42.
Meng J, Zhang D, Pan N, et al. Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis. PeerJ. 2015;3:e971.PubMedPubMedCentral
43.
van der Ree MH, Jansen L, Kruize Z, et al. Plasma microRNA levels are associated with hepatitis B e antigen status and treatment response in chronic hepatitis B patients. J Infect Dis. 2017;215(9):1421–1429.PubMed
Metadata
Title
MiR-194-5p in Pancreatic Ductal Adenocarcinoma Peritoneal Washings is Associated with Peritoneal Recurrence and Overall Survival in Peritoneal Cytology-Negative Patients
Authors
Hirokazu Kubo, MD
Yukihiko Hiroshima, MD, PhD
Ryutaro Mori, MD, PhD
Yusuke Saigusa, PhD
Takashi Murakami, MD, PhD
Yasuhiro Yabushita, MD, PhD
Yu Sawada, MD, PhD
Yuki Homma, MD, PhD
Takafumi Kumamoto, MD, PhD
Ryusei Matsuyama, MD, PhD
Itaru Endo, MD, PhD
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2019
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07793-y

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