Overexpression of microRNA‑130a predicts adverse prognosis of primary gastrointestinal diffuse large B‑cell lymphoma

Chen,Leiyuan; Kan,Yutian; Wang,Xinyuan; Ge,Peng; Ding,Tingting; Zhai,Qiongli; Wang,Yafei; Yu,Yong; Wang,Xiaofang; Zhao,Zhigang; Yang,Hongliang; Liu,Xianming; Li,Lanfang; Qiu,Lihua; Zhang,Huilai; Qian,Zhengzi; Zhao,Haifeng

doi:10.3892/ol.2020.11954

Overexpression of microRNA‑130a predicts adverse prognosis of primary gastrointestinal diffuse large B‑cell lymphoma

Authors:
- Leiyuan Chen
- Yutian Kan
- Xinyuan Wang
- Peng Ge
- Tingting Ding
- Qiongli Zhai
- Yafei Wang
- Yong Yu
- Xiaofang Wang
- Zhigang Zhao
- Hongliang Yang
- Xianming Liu
- Lanfang Li
- Lihua Qiu
- Huilai Zhang
- Zhengzi Qian
- Haifeng Zhao
View Affiliations

Affiliations: Department of Hematology and Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Laboratory, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Pathology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China, Department of Lymphoma, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Clinical Research Center for Cancer, Tianjin 300060, P.R. China
Published online on: August 6, 2020 https://doi.org/10.3892/ol.2020.11954
Article Number: 93
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Primary gastrointestinal diffuse large B‑cell lymphoma (PGI‑DLBCL) is a highly heterogeneous type of non‑Hodgkin lymphoma. A number of studies have demonstrated that microRNA‑130a (miR‑130a) serves a role in the tumorigenesis and prognosis of numerous human tumors. However, to the best of our knowledge, the prognostic significance of miR‑130a in PGI‑DLBCL remains unknown. The present study explored the association between miR‑130a and the clinical outcomes of PGI‑DLBCL. Relative miR‑130a expression was assessed by reverse transcription‑quantitative PCR. Immunohistochemistry was used to detect expression levels of BCL‑2, c‑MYC, neprilysin, B‑cell lymphoma 6 protein, PWWP domain‑containing DNA repair factor 3A and proliferation marker protein Ki‑67. A receiver operating characteristic curve was constructed to analyze the specificity and sensitivity of microRNA levels in the diagnosis of PGI‑DLBCL. Survival curves were constructed using the Kaplan‑Meier method. In the present study, miR‑130a expression was notably higher in patients with PGI‑DLBCL compared with in the controls (P<0.0001). miR‑130a overexpression was closely associated with a high International Prognostic Index score (3‑5) and drug resistance (P=0.017 and P=0.044, respectively). No significant difference in other clinical features was observed. Patients with increased expression levels of miR‑130a had lower overall survival [hazard ratio (HR), 2.998; 95% CI, 1.347‑6.673; P=0.007] and progression‑free survival (HR, 3.325; 95% CI, 1.488‑7.429; P=0.003) compared with patients who had lower expression levels of miR‑130a. Furthermore, multivariate Cox regression analysis suggested that miR‑130a was a negative prognostic parameter in PGI‑DLBCL. Therefore, upregulation of miR‑130a could become a potential prognostic marker for PGI‑DLBCL. Additionally, further study of these results may have important guiding significance for the prognosis of patients with PGI‑DLBCL in the clinical setting.

View Figures

View References

1	Freeman C, Berg JW and Cutler SJ: Occurrence and prognosis of extranodal lymphomas. Cancer. 29:252–260. 1972. View Article : Google Scholar : PubMed/NCBI
2	Berglund M, Hedström G, Amini RM, Enblad G and Thunberg U: High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma. Oncol Rep. 29:720–724. 2013. View Article : Google Scholar : PubMed/NCBI
3	Papaxoinis G, Papageorgiou S, Rontogianni D, Kaloutsi V, Fountzilas G, Pavlidis N, Dimopoulos M, Tsatalas C, Xiros N and Economopoulos T: Primary gastrointestinal non-Hodgkin's lymphoma: A clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG). Leuk Lymphoma. 47:2140–2146. 2006. View Article : Google Scholar : PubMed/NCBI
4	Herrmann R, Panahon AM, Barcos MP, Walsh D and Stutzman L: Gastrointestinal involvement in non-Hodgkin's lymphoma. Cancer. 46:215–222. 1980. View Article : Google Scholar : PubMed/NCBI
5	Müller AM, Ihorst G, Mertelsmann R and Engelhardt M: Epidemiology of non-Hodgkin's lymphoma (NHL): Trends, geographic distribution, and etiology. Ann Hematol. 84:1–12. 2005. View Article : Google Scholar : PubMed/NCBI
6	Malipatel R, Patil M, Pritilata Rout P, Correa M and Devarbhavi H: Primary gastric lymphoma: Clinicopathological profile. Euroasian J Hepatogastroenterol. 8:6–10. 2018.PubMed/NCBI
7	Xia B, Zhang L, Guo SQ, Li XW, Qu FL, Zhao HF, Zhang LY, Sun BC, You J and Zhang YZ: Coexpression of MYC and BCL-2 predicts prognosis in primary gastrointestinal diffuse large B-cell lymphoma. World J Gastroenterol. 21:2433–2442. 2015. View Article : Google Scholar : PubMed/NCBI
8	Peng JC, Zhong L and Ran ZH: Primary lymphomas in the gastrointestinal tract. J Dig Dis. 16:169–176. 2015. View Article : Google Scholar : PubMed/NCBI
9	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
10	Zhao H, Zhang L, Guo S, Yuan T, Xia B, Qu F, Zhang L and Zhang Y: Downregulated expression of Dicer1 predicts inferior survival in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab. Med Oncol. 31:2062014. View Article : Google Scholar : PubMed/NCBI
11	Treiber T, Treiber N and Meister G: Regulation of microRNA biogenesis and function. Thromb Haemost. 107:605–610. 2012. View Article : Google Scholar : PubMed/NCBI
12	Chen X, Lu P, Wang DD, Yang SJ, Wu Y, Shen HY, Zhong SL, Zhao JH and Tang JH: The role of miRNAs in drug resistance and prognosis of breast cancer formalin-fixed paraffin-embedded tissues. Gene. 595:221–226. 2016. View Article : Google Scholar : PubMed/NCBI
13	Wang D, Qiu C, Zhang H, Wang J, Cui Q and Yin Y: Human microRNA oncogenes and tumor suppressors show significantly different biological patterns: from functions to targets. PLoS One. 5:e130672010. View Article : Google Scholar : PubMed/NCBI
14	Xiong J, Wei B, Ye Q and Liu W: MiR-30a-5p/UBE3C axis regulates breast cancer cell proliferation and migration. Biochem Biophys Res Commun. 516:1013–1018. 2016. View Article : Google Scholar : PubMed/NCBI
15	Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, et al: A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 353:1793–1801. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, et al: Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 141:672–675. 2008. View Article : Google Scholar : PubMed/NCBI
17	Zhang HD, Jiang LH, Sun DW, Li J and Ji ZL: The role of miR-130a in cancer. Breast Cancer. 24:521–527. 2017. View Article : Google Scholar : PubMed/NCBI
18	Jiang H, Yu WW, Wang LL and Peng Y: miR-130a acts as a potential diagnostic biomarker and promotes gastric cancer migration, invasion and proliferation by targeting RUNX3. Oncol Rep. 34:1153–1161. 2015. View Article : Google Scholar : PubMed/NCBI
19	Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, Li HC and Wu XN: Differential expression of miRNAs in esophageal cancer tissue. Oncol Lett. 5:1639–1642. 2013. View Article : Google Scholar : PubMed/NCBI
20	Ishihara K, Sasaki D, Tsuruda K, Inokuchi N, Nagai K, Hasegawa H, Yanagihara K and Kamihira S: Impact of miR-155 and miR-126 as novel biomarkers on the assessment of disease progression and prognosis in adult T-cell leukemia. Cancer Epidemiol. 36:560–565. 2012. View Article : Google Scholar : PubMed/NCBI
21	Ding C, Chen SN, Macleod RAF, Drexler HG, Nagel S, Wu DP, Sun AN and Dai HP: MiR-130a is aberrantly overexpressed in adult acute myeloid leukemia with t(8;21) and its suppression induces AML cell death. Ups J Med Sci. 123:19–27. 2018. View Article : Google Scholar : PubMed/NCBI
22	Yuan WX, Gui YX, Na WN, Chao J and Yang X: Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients. Oncol Lett. 11:423–432. 2016. View Article : Google Scholar : PubMed/NCBI
23	Li B, Huang P, Qiu J, Liao Y, Hong J and Yuan Y: MicroRNA-130a is down-regulated in hepatocellular carcinoma and associates with poor prognosis. Med Oncol. 31:2302014. View Article : Google Scholar : PubMed/NCBI
24	Kovaleva V, Mora R, Park YJ, Plass C, Chiramel AI, Bartenschlager R, Döhner H, Stilgenbauer S, Pscherer A, Lichter P and Seiffert M: miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells. Cancer Res. 72:1763–1772. 2012. View Article : Google Scholar : PubMed/NCBI
25	Borges NM, do Vale Elias M, Fook-Alves VL, Andrade TA, de Conti ML, Macedo MP, Begnami MD, Campos AH, Etto LY, Bortoluzzo AB, et al: Angiomirs expression profiling in diffuse large B-Cell lymphoma. Oncotarget. 7:4806–4816. 2016. View Article : Google Scholar : PubMed/NCBI
26	Tomonaga M: Outline and direction of revised WHO classification of tumors of haematopoietic and lymphoid tissues. Rinsho Ketsueki. 50:1401–1406. 2009.PubMed/NCBI
27	Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, Lister TA, Norton A, Salem P, Shipp M, et al: Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann. Oncol. 5:397–400. 1994.
28	Sok M, Zavrl M, Greif B and Srpčič M: Objective assessment of WHO/ECOG performance status. Support Care Cancer. 27:3793–3798. 2019. View Article : Google Scholar : PubMed/NCBI
29	Ghimire P, Wu GY and Zhu L: Primary gastrointestinal lymphoma. World J. Gastroenterol. 17:697–707. 2011.
30	Chen F, Liu S, Zhou Y, Shen H and Zuo X: Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma. Hematology. 21:399–403. 2016. View Article : Google Scholar : PubMed/NCBI
31	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
32	Muris JJ, Meijer CJ, Vos W, van Krieken JH, Jiwa NM, Ossenkoppele GJ and Oudejans JJ: Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol. 208:714–723. 2006. View Article : Google Scholar : PubMed/NCBI
33	Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, et al: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 103:275–282. 2004. View Article : Google Scholar : PubMed/NCBI
34	Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, Klapper W, Hummel M, Stein H, Hansmann ML, et al: MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 121:2253–2263. 2013. View Article : Google Scholar : PubMed/NCBI
35	Juarez-Salcedo LM, Sokol L, Chavez JC and Dalia S: Primary gastric lymphoma, epidemiology, clinical diagnosis, and treatment. Cancer Control. 25:1–12. 2018. View Article : Google Scholar
36	Ahmadvand M, Eskandari M, Pashaiefar H, Yaghmaie M, Manoochehrabadi S, Khakpour G, Sheikhsaran F and Montazer Zohour M: Over expression of circulating miR-155 predicts prognosis in diffuse large B-cell lymphoma. Leuk Res. 70:45–48. 2018. View Article : Google Scholar : PubMed/NCBI
37	Craig VJ, Tzankov A, Flori M, Schmid CA, Bader AG and Muller A: Systemic microRNA-34a delivery induces apoptosis and abrogates growth of diffuse large B-cell lymphoma in vivo. Leukemia. 26:2421–2424. 2012. View Article : Google Scholar : PubMed/NCBI
38	Craig VJ, Cogliatti SB, Imig J, Renner C, Neuenschwander S, Rehrauer H, Schlapbach R, Dirnhofer S, Tzankov A and Müller A: Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 117:6227–6236. 2011. View Article : Google Scholar : PubMed/NCBI
39	Yang F, Miao L, Mei Y and Wu M: Retinoic acid-induced HOXA5 expression is co-regulated by HuR and miR-130a. Cell Signal. 25:1476–1485. 2013. View Article : Google Scholar : PubMed/NCBI
40	Zhou YM, Liu J and Sun W: MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac. J Cancer Prev. 15:1391–1406. 2014.
41	Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q and Zhang J: Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell. Biochem Biophys Res Commun. 425:468–472. 2012. View Article : Google Scholar : PubMed/NCBI
42	Yu X and Li Z: New insights into MicroRNAs involves in drug resistance in diffuse large B cell lymphoma. Am J Transl Res. 7:2536–2542. 2015.PubMed/NCBI
43	Kawamoto K, Miyoshi H, Yoshida N, Nakamura N, Ohshima K, Sone H and Takizawa J: MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B-cell lymphoma. Cancer Sci. 107:853–861. 2016. View Article : Google Scholar : PubMed/NCBI
44	Plati J, Bucur O and Khosravi-Far R: Apoptotic cell signaling in cancer progression and therapy. Integr Biol. 3:279–96. 2011. View Article : Google Scholar
45	Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, Liu WM, Visco C, Li Y, Miranda RN, et al: MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: A report from The International DLBCL Rituximab-CHOP consortium program. Blood. 121:4021–4031. 2013. View Article : Google Scholar : PubMed/NCBI
46	Lim KH, Yang Y and Staudt LM: Pathogenetic importance and therapeutic implications of NF-kB in lymphoid malignancies. Immunol Rev. 246:359–378. 2012. View Article : Google Scholar : PubMed/NCBI
47	Feng Y, Zhou S, Li G, Hu C, Zou W, Zhang H and Sun L: Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog. Arch Biochem Biophys. 598:57–65. 2016. View Article : Google Scholar : PubMed/NCBI
48	Wang Y, Zhang X, Tang W, Lin Z, Xu L, Dong R, Li Y, Li J, Zhang Z, Li X, et al: miR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-κB in high-grade serous ovarian carcinoma. Cell Death Differ. 24:2089–2100. 2017. View Article : Google Scholar : PubMed/NCBI
49	Filip D and Mraz M: The role of MYC in the transformation and aggressiveness of ‘indolent’ B-cell malignancies. Leuk. Lymphoma. 61:510–524. 2019. View Article : Google Scholar
50	Zhu J, Zheng X and Yang X: Diagnostic and mechanistic values of microRNA-130a and microRNA-203 in patients with papillary thyroid carcinoma. J Cell Biochem. 121:3657–3666. 2020. View Article : Google Scholar
51	Nguyen L, Papenhausen P and Shao H: The Role of c-MYC in B-cell lymphomas: Diagnostic and molecular aspects. Genes (Basel). 8:1162017. View Article : Google Scholar
52	Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, et al: Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 30:3452–3459. 2012. View Article : Google Scholar : PubMed/NCBI
53	Lee SH, Jung YD, Choi YS and Lee YM: Targeting of RUNX3 by miR-130a and miR-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. Oncotarget. 6:33269–33278. 2015. View Article : Google Scholar : PubMed/NCBI
54	Wang XC, Tian LL, Wu HL, Jiang XY, Du LQ, Zhang H, Wang YY, Wu HY, Li DG, She Y, et al: Expression of miRNA-130a in nonsmall cell lung cancer. Am J Med Sci. 340:385–388. 2010. View Article : Google Scholar : PubMed/NCBI
55	Zhao H, Zhang LE, Guo S, Yuan T, Xia B, Zhang L and Zhang Y: Overexpression of DNA methyltransferase 1 as a negative independent prognostic factor in primary gastrointestinal diffuse large B-cell lymphoma treated with CHOP-like regimen and rituximab. Oncol Lett. 9:2307–2312. 2015. View Article : Google Scholar : PubMed/NCBI
56	Pallasch CP, Patz M, Park YJ, Hagist S, Eggle D, Claus R, Debey-Pascher S, Schulz A, Frenzel LP, Claasen J, et al: miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia. Blood. 114:3255–3264. 2009. View Article : Google Scholar : PubMed/NCBI
57	Kanagal-Shamanna R: Digital PCR: Principles and Applications. Methods Mol Biol. 1392:43–50. 2016. View Article : Google Scholar : PubMed/NCBI
58	Cao L, Cui X, Hu J, Li Z, Choi JR, Yang Q, Lin M, Ying Hui L and Xu F: Advances in digital polymerase chain reaction (dPCR) and its emerging biomedical applications. Biosens Bioelectron. 90:459–474. 2017. View Article : Google Scholar : PubMed/NCBI