Can Circulating MicroRNAs Predict Colorectal Cancer? Results from a Nested Case-control Study of Pre-diagnostic Serum Samples from Two Prospective Biobanks

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2025 Mar 14

PMID 40082755

Authors

Eva Hofsli

Pal Saetrom

Eivind Ness-Jensen

Helja-Marja Surcel

Robin Mjelle

Affiliations

Soon will be listed here.

Abstract

Background: This study aimed to investigate the potential of circulating small RNAs (sRNAs) as predictive biomarkers for future colorectal cancer (CRC). The study analyzed serum samples from pre-diagnostic CRC patients in two prospective biobanks.

Methods: Serum samples from 142 pre-diagnostic CRC patients, from the Finnish Maternity Cohort (FMC) and The HUNT Study (HUNT2), were subjected to small RNA sequencing. The study compared sRNA expression in CRC cases with controls, considering diverse sRNA classes.

Results: Analysis revealed diverse miRNA expression patterns with notable variations in future metastatic cases. Specifically, miR-223-3p and miR-21-5p showed significant up-regulation in future metastatic cases in the FMC cohort. Consistent changes were observed across cohorts, with miR-584-5p, miR-30c-5p, miR-146a-5p, miR-10a-5p, and miR-1306-5p showing up-regulation in future metastatic cases.

Conclusions: The study identified potential serum miRNA biomarkers associated with metastatic CRC, though statistical significance varied. These findings contribute to the understanding of miRNA profiles in pre-diagnostic CRC patients, emphasizing the need for further exploration of non-invasive biomarkers in large prospective studies.

References

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

MORSON B . The evolution of colorectal carcinoma. Clin Radiol. 1984; 35(6):425-31. DOI: 10.1016/s0009-9260(84)80033-1. View

OBrien M, Gibbons D . The adenoma-carcinoma sequence in colorectal neoplasia. Surg Oncol Clin N Am. 1996; 5(3):513-30. View

Petrelli F, Tomasello G, Borgonovo K, Ghidini M, Turati L, Dallera P . Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016; 3(2):211-219. DOI: 10.1001/jamaoncol.2016.4227. View

Roy Chowdhury M, Hone K, Prevost K, Balthazar P, Avino M, Arguin M . Optimizing Fecal Occult Blood Test (FOBT) Colorectal Cancer Screening Using Gut Bacteriome as a Biomarker. Clin Colorectal Cancer. 2023; 23(1):22-34.e2. DOI: 10.1016/j.clcc.2023.10.004. View

Moayyedi P, Achkar E . Does fecal occult blood testing really reduce mortality? A reanalysis of systematic review data. Am J Gastroenterol. 2006; 101(2):380-4. DOI: 10.1111/j.1572-0241.2006.00537.x. View

Mosadeghi S, Ren H, Catungal J, Yen I, Liu B, Wong R . Utilization of fecal occult blood test in the acute hospital setting and its impact on clinical management and outcomes. J Postgrad Med. 2016; 62(2):91-5. PMC: 4944357. DOI: 10.4103/0022-3859.180553. View

Blom J, Saraste D, Tornberg S, Jonsson H . Routine Fecal Occult Blood Screening and Colorectal Cancer Mortality in Sweden. JAMA Netw Open. 2024; 7(2):e240516. PMC: 10900849. DOI: 10.1001/jamanetworkopen.2024.0516. View

Lee M, Pourmorady J, Laine L . Use of Fecal Occult Blood Testing as a Diagnostic Tool for Clinical Indications: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2020; 115(5):662-670. DOI: 10.14309/ajg.0000000000000495. View

10.

Mitchell P, Parkin R, Kroh E, Fritz B, Wyman S, Pogosova-Agadjanyan E . Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008; 105(30):10513-8. PMC: 2492472. DOI: 10.1073/pnas.0804549105. View

11.

Schwarzenbach H, Nishida N, Calin G, Pantel K . Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014; 11(3):145-56. DOI: 10.1038/nrclinonc.2014.5. View

12.

Kupec T, Bleilevens A, Iborra S, Najjari L, Wittenborn J, Maurer J . Stability of circulating microRNAs in serum. PLoS One. 2022; 17(8):e0268958. PMC: 9432728. DOI: 10.1371/journal.pone.0268958. View

13.

Keller A, Leidinger P, Gislefoss R, Haugen A, Langseth H, Staehler P . Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis. RNA Biol. 2011; 8(3):506-16. DOI: 10.4161/rna.8.3.14994. View

14.

Peng Y, Croce C . The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2017; 1:15004. PMC: 5661652. DOI: 10.1038/sigtrans.2015.4. View

15.

Schetter A, Okayama H, Harris C . The role of microRNAs in colorectal cancer. Cancer J. 2012; 18(3):244-52. PMC: 3397427. DOI: 10.1097/PPO.0b013e318258b78f. View

16.

Hofsli E, Sjursen W, Prestvik W, Johansen J, Rye M, Trano G . Identification of serum microRNA profiles in colon cancer. Br J Cancer. 2013; 108(8):1712-9. PMC: 3668463. DOI: 10.1038/bjc.2013.121. View

17.

Mjelle R, Sellaeg K, Saetrom P, Thommesen L, Sjursen W, Hofsli E . Identification of metastasis-associated microRNAs in serum from rectal cancer patients. Oncotarget. 2017; 8(52):90077-90089. PMC: 5685733. DOI: 10.18632/oncotarget.21412. View

18.

Imaoka H, Toiyama Y, Fujikawa H, Hiro J, Saigusa S, Tanaka K . Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. Ann Oncol. 2016; 27(10):1879-86. DOI: 10.1093/annonc/mdw279. View

19.

Asvold B, Langhammer A, Rehn T, Kjelvik G, Grontvedt T, Sorgjerd E . Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol. 2022; 52(1):e80-e91. PMC: 9908054. DOI: 10.1093/ije/dyac095. View

20.

Lehtinen M, Surcel H, Natunen K, Pukkala E, Dillner J . Cancer Registry follow-up for 17 million person-years of a nationwide maternity cohort. Cancer Med. 2017; 6(12):3060-3064. PMC: 5727241. DOI: 10.1002/cam4.1222. View