• This record comes from PubMed

An Independent Validation Study of Candidate microRNAs as Predictive Biomarkers for Bevacizumab-based Therapy in Patients With Metastatic Colorectal Cancer

. 2021 Sep-Oct ; 35 (5) : 2809-2814.

Language English Country Greece Media print

Document type Journal Article

BACKGROUND/AIM: The monoclonal antibody bevacizumab is a standard drug used in combination with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) based chemotherapy in the first or second-line treatment of metastatic colorectal cancer (mCRC). Our previous study identified and subsequently validated 4 microRNAs in a small group of patients as predictors of the therapeutic response to bevacizumab combined with chemotherapy. The aim of this follow-up study is to confirm the predictive ability of these tissue miRNAs in a larger independent cohort of mCRC patients. PATIENTS AND METHODS: The retrospective study included 92 patients with generalized-radically inoperable tumors treated with the combined therapy of bevacizumab/FOLFOX in a standard regimen. RESULTS: Expression levels of candidate miRNA biomarkers (miR-92b-3p, miR-3156-5p, miR-10a-5p and miR-125a-5p) were determined in tumor tissue specimens and statistically evaluated. MiR-92b-3p and miR-125a-5p were confirmed to be associated with radiological response according to RECIST criteria (p=0.005 and 0.05, respectively) and to be up-regulated in responders to bevacizumab/FOLFOX therapy. Higher levels of miR-92b-3p were also significantly associated with extended progression-free survival (p=0.024). CONCLUSION: We have successfully confirmed miR-92b-3p to be up-regulated in tumor tissue of mCRC patients with good response to bevacizumab/FOLFOX therapy.

See more in PubMed

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F. Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer, 2018. . Available at: https://gco.iarc.fr/today. [Last accessed on June 8, 2021]

Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–2019. doi: 10.1200/JCO.2007.14.9930. PubMed DOI

Pai SG, Fuloria J. Novel therapeutic agents in the treatment of metastatic colorectal cancer. World J Gastrointest Oncol. 2016;8(1):99–104. doi: 10.4251/wjgo.v8.i1.99. PubMed DOI PMC

Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009;8:102. doi: 10.1186/1476-4598-8-102. PubMed DOI PMC

Annese T, Tamma R, De Giorgis M, Ribatti D. microRNAs biogenesis, functions and role in tumor angiogenesis. Front Oncol. 2020;10:581007. doi: 10.3389/fonc.2020.581007. PubMed DOI PMC

Goblirsch M, Richtig G, Slaby O, Berindan-Neagoe I, Gerger A, Pichler M. MicroRNAs as a tool to aid stratification of colorectal cancer patients and to guide therapy. Pharmacogenomics. 2017;18(10):1027–1038. doi: 10.2217/pgs-2017-0004. PubMed DOI

Kiss I, Mlčochová J, Součková K, Fabian P, Poprach A, Halamkova J, Svoboda M, Vyzula R, Slaby O. MicroRNAs as outcome predictors in patients with metastatic colorectal cancer treated with bevacizumab in combination with FOLFOX. Oncol Lett. 2017;14(1):743–750. doi: 10.3892/ol.2017.6255. PubMed DOI PMC

Fiala O, Pitule P, Hosek P, Liska V, Sorejs O, Bruha J, Vycital O, Buchler T, Poprach A, Topolcan O, Finek J. The association of miR-126-3p, miR-126-5p and miR-664-3p expression profiles with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. Tumour Biol. 2017;39(7):1010428317709283. doi: 10.1177/1010428317709283. PubMed DOI

Poel D, Gootjes EC, Bakkerus L, Trypsteen W, Dekker H, van der Vliet HJ, van Grieken NCT, Verhoef C, Buffart TE, Verheul HMW. A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer. Cancer Med. 2020;9(20):7558–7571. doi: 10.1002/cam4.3371. PubMed DOI PMC

Jiang L, Huang Q, Chang J, Wang E, Qiu X. MicroRNA HSA-miR-125a-5p induces apoptosis by activating p53 in lung cancer cells. Exp Lung Res. 2011;37(7):387–398. doi: 10.3109/01902148.2010.492068. PubMed DOI

Jiang L, Chang J, Zhang Q, Sun L, Qiu X. MicroRNA hsa-miR-125a-3p activates p53 and induces apoptosis in lung cancer cells. Cancer Invest. 2013;31(8):538–544. doi: 10.3109/07357907.2013.820314. PubMed DOI

Hsieh TH, Hsu CY, Tsai CF, Long CY, Chai CY, Hou MF, Lee JN, Wu DC, Wang SC, Tsai EM. miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis. Oncotarget. 2015;6(1):494–509. doi: 10.18632/oncotarget.2674. PubMed DOI PMC

Ma G, Jing C, Li L, Huang F, Ding F, Wang B, Lin D, Luo A, Liu Z. MicroRNA-92b represses invasion-metastasis cascade of esophageal squamous cell carcinoma. Oncotarget. 2016;7(15):20209–20222. doi: 10.18632/oncotarget.7747. PubMed DOI PMC

Long M, Zhan M, Xu S, Yang R, Chen W, Zhang S, Shi Y, He Q, Mohan M, Liu Q, Wang J. miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer. Mol Cancer. 2017;16(1):167. doi: 10.1186/s12943-017-0723-7. PubMed DOI PMC

Ye Z, Shi J, Ning Z, Hou L, Hu CY, Wang C. MiR-92b-3p inhibits proliferation and migration of C2C12 cells. Cell Cycle. 2020;19(21):2906–2917. doi: 10.1080/15384101.2020.1827511. PubMed DOI PMC

Xu T, Wang H, Jiang M, Yan Y, Li W, Xu H, Huang Q, Lu Y, Chen J. The E3 ubiquitin ligase CHIP/miR-92b/PTEN regulatory network contributes to tumorigenesis of glioblastoma. Am J Cancer Res. 2017;7(2):289–300. PubMed PMC

Gong L, Ren M, Lv Z, Yang Y, Wang Z. miR-92b-3p promotes colorectal carcinoma cell proliferation, invasion, and migration by inhibiting FBXW7 in vitro and in vivo. DNA Cell Biol. 2018;37(5):501–511. doi: 10.1089/dna.2017.4080. PubMed DOI

Zhang W, Duan W, Mo Z, Wang J, Yang W, Wu W, Li X, Lin S, Tan Y, Wei W. Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR-92b-3p. J Cell Biochem. 2020;121(2):1998–2008. doi: 10.1002/jcb.29434. PubMed DOI

Lee J, Heo J, Kang H. miR-92b-3p-TSC1 axis is critical for mTOR signaling-mediated vascular smooth muscle cell proliferation induced by hypoxia. Cell Death Differ. 2019;26(9):1782–1795. doi: 10.1038/s41418-018-0243-z. PubMed DOI PMC

Hao X, Ma C, Chen S, Dang J, Cheng X, Zhu D. Reverse the down regulation of miR-92b-3p by hypoxia can suppress the proliferation of pulmonary artery smooth muscle cells by targeting USP28. Biochem Biophys Res Commun. 2018;503(4):3064–3077. doi: 10.1016/j.bbrc.2018.08.095. PubMed DOI

Wang J, Wang C, Li Y, Li M, Zhu T, Shen Z, Wang H, Lv W, Wang X, Cheng X, Xie X. Potential of peptide-engineered exosomes with overexpressed miR-92b-3p in anti-angiogenic therapy of ovarian cancer. Clin Transl Med. 2021;11(5):e425. doi: 10.1002/ctm2.425. PubMed DOI PMC

Li M, Shan W, Hong B, Zou J, Li H, Han D, Zhang Y, Li L, Li D, Lin W. Circulating miR-92b and miR-375 for monitoring the chemoresistance and prognosis of small cell lung cancer. Sci Rep. 2020;10(1):12705. doi: 10.1038/s41598-020-69615-6. PubMed DOI PMC

Uotani K, Fujiwara T, Yoshida A, Iwata S, Morita T, Kiyono M, Yokoo S, Kunisada T, Takeda K, Hasei J, Numoto K, Nezu Y, Yonemoto T, Ishii T, Kawai A, Ochiya T, Ozaki T. Circulating MicroRNA-92b-3p as a novel biomarker for monitoring of synovial sarcoma. Sci Rep. 2017;7(1):14634. doi: 10.1038/s41598-017-12660-5. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...