Prospects of differential diagnosis of focal lesion of pancreas by the microRNA assessment
https://doi.org/10.37748/2686-9039-2023-4-3-3
EDN: GUGSOK
Abstract
Purpose of the study. Identification of potential miRNA markers in material of focal pancreatic lesions.
Materials and methods. Samples of focal pancreatic lesions after histological evaluation were enrolled in the study including chronic pancreatitis (ChP) (n = 23), low-grade pancreatic intraepithelial neoplasia /PanIN‑1/2 (n = 19), high-grade pancreatic intraepithelial neoplasia /PanIN‑3 (n = 8), and invasive pancreatic ductal adenocarcinoma PDAC (n = 26). Workflow of research included the profiling of cancer-associated miRNA in pooled samples, the selection of potential marker miRNAs, the assessment of selected miRNAs expression in total collection of specimens, the identification of differentially expressed miRNAs, and the approbation of new algorithm of data interpretation via ratio of “reciprocal miRNA pair”. Consequent reactions of revers transcription and quantitative teal-time PCR were used.
Results. The expression levels of miR‑216a and miR‑217 were decreased in the following order: PanIN‑1/2 > PanIN‑3 > PDAC. Moreover, miR‑375 was up-regulated while miR‑143 was down-regulated in the PDAC. Differential diagnostics of PDAC versus focal chronic pancreatitis might be performed with high accuracy (AUC > 0.95) by assessment panel of four molecules: miR‑216a, miR‑217, miR‑1246 and Let‑7a.
Conclusion. The assessment of microRNAs in pancreatic lesions is a promising approach for the differential diagnosis of PDAC, but this technology requires further validation with an increase in the number of samples.
About the Authors
M. S. KniazevaRussian Federation
Margarita S. Kniazeva – junior researcher at the laboratory of sub-cellular technologies, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0002-2079-5061, SPIN: 1435-9601, AuthorID: 1170597, Scopus Author ID: 57201116352
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
T. M. Shestopalova
Russian Federation
Tatyana M. Shestopalova – MD, pathologist, physician at the clinical laboratory diagnostics, National Center for Clinical Morphological Diagnostics, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0001-8615-6273, SPIN: 7579-0951, AuthorID: 1183632
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
L. M. Zabegina
Russian Federation
Lidia M. Zabegina – junior researcher at the laboratory of sub-cellular technologies, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0003-0827-1641, SPIN: 9886-7610, AuthorID: 1108887, Scopus Author ID: 57218621246
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
A. V. Shalaev
Russian Federation
Andrey V. Shalaev – junior researcher at the laboratory of sub-cellular technologies, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0002-6148-6994, SPIN: 9971-1945, AuthorID: 1165260, Scopus Author ID: 57211294093
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
A. K. Ratnikova
Russian Federation
Anna K. Ratnikova – Cand. Sci. (Med.), MD, cardiologist of the highest category, junior researcher, North-Western District Scientific and Clinical Center named after L. G. Sokolov, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0003-3279-6448, SPIN: 4086-7164, AuthorID: 1076748
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
V. A. Kashchenko
Russian Federation
Victor A. Kashchenko – Dr. Sci. (Med.), professor, Deputy CEO for scientific and educational work, North-Western District Scientific and Clinical Center named after L. G. Sokolov, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0002-4958-5850, SPIN: 9814-3956, AuthorID: 340730, Researcher ID: K-8778-2015, Scopus Author ID: 7003374162
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
S. L. Vorobyev
Russian Federation
Sergey L. Vorobyev – Cand. Sci. (Med.), MD, pathologist, director, National Center for Clinical Morphological Diagnostics, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0002-7817-9069, SPIN: 5920-0603, AuthorID: 934523
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
A. V. Malek
Russian Federation
Anastasia V. Malek – Dr. Sci. (Med.), head of the laboratory of sub-cellular technologies, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russian Federation.
ORCID: https://orcid.org/0000-0001-5334-7292, SPIN: 6445-3432, AuthorID: 129474, ResearcherID: R-8804-2016, Scopus Author ID: 35741075000
Competing Interests:
the authors state that there are no conflicts of interest to disclose.
References
1. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Edited by A. D. Kaprin, V. V. Starinsky, A. O. Shakhzadova. Moscow: P. A. Herzen MNIOI – Branch of the National Medical Research Radiological Center, 2021, 252 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2021/11/zis-2020-elektronnaya-versiya.pdf, Accessed: 06/20/2023.
2. Merabishvili M. V. Survival of cancer patients. Issue two. Issue 2, part 1; St. Petersburg, 2011, 329 p. (In Russ.).
3. Kaprin AD. Clinical recommendations. Pancreatic cancer. Scientific Council of the Ministry of Health of the Russian Federation, 2019, 67 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2020/09/ rak_podzheludochnoj_zhelezy.pdf, Accessed: 06/20/2023.
4. Yang J, Xu R, Wang C, Qiu J, Ren B, You L. Early screening and diagnosis strategies of pancreatic cancer: a comprehensive review. Cancer Commun (Lond). 2021 Dec;41(12):1257–1274. https://doi.org/10.1002/cac2.12204
5. Sharma A, Kandlakunta H, Nagpal SJS, Feng Z, Hoos W, Petersen GM, et al. Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes. Gastroenterology. 2018 Sep;155(3):730–739.e3. https://doi.org/10.1053/j.gastro.2018.05.023
6. Madhavan B, Yue S, Galli U, Rana S, Gross W, Müller M, et al. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer. 2015 Jun 1;136(11):2616–2627. https://doi.org/10.1002/ijc.29324
7. Michálková L, Horník Š, Sýkora J, Habartová L, Setnička V. Diagnosis of pancreatic cancer via1H NMR metabolomics of human plasma. Analyst. 2018 Dec 3;143(24):5974–5978. https://doi.org/10.1039/c8an01310a
8. Bunganič B, Laclav M, Dvořáková T, Bradáč O, Traboulsi E, Suchánek Š, et al. Accuracy of EUS and CEH EUS for the diagnosis of pancreatic tumours. Scand J Gastroenterol. 2018;53(10–11):1411–1417. https://doi.org/10.1080/00365521.2018.1524023
9. Facciorusso A, Martina M, Buccino RV, Nacchiero MC, Muscatiello N. Diagnostic accuracy of fine-needle aspiration of solid pancreatic lesions guided by endoscopic ultrasound elastography. Ann Gastroenterol. 2018;31(4):513–518. https://doi.org/10.20524/aog.2018.0271
10. Mikhetko AA, Artemyeva AS, Ivko OV, Tkachenko OB, Grinkevich MV, Sidorova AN, et al. Endoscopic endosonography with fine needle aspiration biopsy in the diagnosis of pancreatic tumors. Questions of Oncology. 2021;67(3):397–404. (In Russ.). https://doi.org/10.37469/0507-3758-2021-67-3-397-404
11. Daoud, A.Z.; Mulholland, E.J.; Cole, G.; McCarthy, H.O. MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators. BMC Cancer 2019, 19, 1130. https://doi.org/10.1186/s12885-019-6284-y.
12. Ariston Gabriel AN, Wang F, Jiao Q, Yvette U, Yang X, Al-Ameri SA, et al. The involvement of exosomes in the diagnosis and treatment of pancreatic cancer. Mol Cancer. 2020 Aug 27;19(1):132. https://doi.org/10.1186/s12943-020-01245-y
13. Fathi M, Ghafouri-Fard S, Abak A, Taheri M. Emerging roles of miRNAs in the development of pancreatic cancer. Biomed Pharmacother. 2021 Sep;141:111914. https://doi.org/10.1016/j.biopha.2021.111914
14. O’Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol. 2021 Jul 14;27(26):4045–4087. https://doi.org/10.3748/wjg.v27.i26.4045
15. Sohrabi E, Rezaie E, Heiat M, Sefidi-Heris Y. An Integrated Data Analysis of mRNA, miRNA and Signaling Pathways in Pancreatic Cancer. Biochem Genet. 2021 Oct;59(5):1326–1358. https://doi.org/10.1007/s10528-021-10062-x
16. Androvic P, Valihrach L, Elling J, Sjoback R, Kubista M. Two-tailed RT-qPCR: a novel method for highly accurate miRNA quantification. Nucleic Acids Res. 2017 Sep 6;45(15):e144. https://doi.org/10.1093/nar/gkx588
17. Andersen CL, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res. 2004 Aug 1;64(15):5245–5250. https://doi.org/10.1158/0008-5472.CAN-04-0496
18. Keller A, Gröger L, Tschernig T, Solomon J, Laham O, Schaum N, et al. miRNATissueAtlas2: an update to the human miRNA tissue atlas. Nucleic Acids Res. 2022 Jan 7;50(D1):D211–D221. https://doi.org/10.1093/nar/gkab808
19. Yonemori K, Kurahara H, Maemura K, Natsugoe S. MicroRNA in pancreatic cancer. J Hum Genet. 2017 Jan;62(1):33–40. https://doi.org/10.1038/jhg.2016.59
20. Hasegawa S, Eguchi H, Nagano H, Konno M, Tomimaru Y, Wada H, et al. MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. Br J Cancer. 2014 Oct 14;111(8):1572–1580. https://doi.org/10.1038/bjc.2014.454
21. Ta N, Huang X, Zheng K, Zhang Y, Gao Y, Deng L, et al. miRNA-1290 Promotes Aggressiveness in Pancreatic Ductal Adenocarcinoma by Targeting IKK1. Cell Physiol Biochem. 2018;51(2):711–728. https://doi.org/10.1159/000495328
22. Szafranska AE, Davison TS, John J, Cannon T, Sipos B, Maghnouj A, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene. 2007 Jun 28;26(30):4442– 4452. https://doi.org/10.1038/sj.onc.1210228
23. Hong TH, Park IY. MicroRNA expression profiling of diagnostic needle aspirates from surgical pancreatic cancer specimens. Ann Surg Treat Res. 2014 Dec;87(6):290–297. https://doi.org/10.4174/astr.2014.87.6.290
24. Korobkina EA, Knyazeva MS, Kil YV, Titov SE, Malek AV. Comparative analysis of RT-qPCR based methodologies for microRNA detection. Klin Lab Diagn. 2018;63(11):722–728. https://doi.org/10.18821/0869-2084-2018-63-11-722-728
25. Marabita F, de Candia P, Torri A, Tegnér J, Abrignani S, Rossi RL. Normalization of circulating microRNA expression data obtained by quantitative real-time RT-PCR. Brief Bioinform. 2016 Mar;17(2):204–212. https://doi.org/10.1093/bib/bbv056
26. Knyazeva M, Korobkina E, Karizky A, Sorokin M, Buzdin A, Vorobyev S, et al. Reciprocal Dysregulation of MiR-146b and MiR451 Contributes in Malignant Phenotype of Follicular Thyroid Tumor. Int J Mol Sci. 2020 Aug 19;21(17):5950. https://doi.org/10.3390/ijms21175950
27. Xie F, Li C, Zhang X, Peng W, Wen T. MiR-143-3p suppresses tumorigenesis in pancreatic ductal adenocarcinoma by targeting KRAS. Biomed Pharmacother. 2019 Nov;119:109424. https://doi.org/10.1016/j.biopha.2019.109424
28. Hu Y, Ou Y, Wu K, Chen Y, Sun W. MiR-143 inhibits the metastasis of pancreatic cancer and an associated signaling pathway. Tumour Biol. 2012 Dec;33(6):1863–1870. https://doi.org/10.1007/s13277-012-0446-8
29. Wei J, Yang L, Wu YN, Xu J. Serum miR-1290 and miR-1246 as Potential Diagnostic Biomarkers of Human Pancreatic Cancer. J Cancer. 2020;11(6):1325–1333. https://doi.org/10.7150/jca.38048
30. Xu YF, Hannafon BN, Khatri U, Gin A, Ding WQ. The origin of exosomal miR-1246 in human cancer cells. RNA Biol. 2019 Jun;16(6):770–784. https://doi.org/10.1080/15476286.2019.1585738
31. Knyazeva MS, Zabelina LM, Koneva OM, Lyutynsky VV, Smirnova OA, Zhamoidik VI, et al. Assessment of the severity of cervical dysplasia by analyzing microRNA in the cervical smear material. Oncogynecology. 2022;(3(43)):57–68. https://doi.org/10.52313/22278710_2022_3_57, EDN: NCDHZF
Supplementary files
Review
For citations:
Kniazeva M.S., Shestopalova T.M., Zabegina L.M., Shalaev A.V., Ratnikova A.K., Kashchenko V.A., Vorobyev S.L., Malek A.V. Prospects of differential diagnosis of focal lesion of pancreas by the microRNA assessment. South Russian Journal of Cancer. 2023;4(3):20-35. https://doi.org/10.37748/2686-9039-2023-4-3-3. EDN: GUGSOK