MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients
Abstract
:1. Introduction
1.1. Incidence and Mortality of CRC
1.2. Searching for New Markers
1.3. The Concept of Liquid Biopsy
1.4. Applying the Challenges of Modern Oncology Diagnostics
2. Results
2.1. Patients’ Characteristics
2.2. The Potential of CEA and CA 19-9 Concentrations in Discriminating against Pre-CRC and CRC Patients
2.3. The Potential of miRNA Expression Levels in Discriminating against Pre-CRC and CRC Patients
2.4. Logistic Regression
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Isolation of Tissue and Circulating miRNAs
4.3. qPCR (RT-qPCR)
4.4. Pathohistological Analysis
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Gašpar, M.Š.; Pavić, J. Prikaz incidencije i mortaliteta raka debelog crijeva u Republici Hrvatskoj. Croat. Nurs. J. 2023, 7, 173–182. [Google Scholar] [CrossRef]
- Santos, D.A.R.; Gaiteiro, C.; Santos, M.; Santos, L.; Dinis-Ribeiro, M.; Lima, L. MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening—A Comprehensive Review. Int. J. Mol. Sci. 2023, 24, 11023. [Google Scholar] [CrossRef] [PubMed]
- Howlader, N.; Noone, A.M.; Krapcho, M.; Miller, D.; Bishop, K.; Altekruse, S.F.; Kosary, C.L.; Yu, M.; Ruhl, J.; Tatalovich, Z.; et al. (Eds.) SEER Cancer Statistics Review, 1975–2013; National Cancer Institute: Bethesda, MD, USA, 2016; Based on November 2015 SEER Data Submission, Posted to the SEER Web Site, April 2016. Available online: https://seer.cancer.gov/archive/csr/1975_2013/ (accessed on 1 May 2024).
- Das, V.; Kalita, J.; Pal, M. Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges. Biomed. Pharmacother. 2017, 87, 8–19. [Google Scholar] [CrossRef] [PubMed]
- Locker, G.Y.; Hamilton, S.; Harris, J.; Jessup, J.M.; Kemeny, N.; Macdonald, J.S.; Somerfield, M.R.; Hayes, D.F.; Bast, R.C., Jr. ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. J. Clin. Oncol. 2006, 24, 5313–5327. [Google Scholar] [CrossRef] [PubMed]
- Duffy, M.; van Dalen, A.; Haglund, C.; Hansson, L.; Holinski-Feder, E.; Klapdor, R.; Lamerz, R.; Peltomaki, P.; Sturgeon, C.; Topolcan, O. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur. J. Cancer 2007, 43, 1348–1360. [Google Scholar] [CrossRef] [PubMed]
- Kawamura, Y.J.; Tokumitsu, A.; Mizokami, K.; Sasaki, J.; Tsujinaka, S.; Konishi, F. First Alert for Recurrence During Follow-up After Potentially Curative Resection for Colorectal Carcinoma: CA 19-9 Should Be Included in Surveillance Programs. Clin. Color. Cancer 2010, 9, 48–51. [Google Scholar] [CrossRef]
- Tan, E.; Gouvas, N.; Nicholls, R.J.; Ziprin, P.; Xynos, E.; Tekkis, P.P. Diagnostic precision of carcinoembryonic antigen in the detection of recurrence of colorectal cancer. Surg. Oncol. 2008, 18, 15–24. [Google Scholar] [CrossRef]
- Lee, W.-S.; Baek, J.-H.; Kim, K.K.; Park, Y.H. The prognostic significant of percentage drop in serum CEA post curative resection for colon cancer. Surg. Oncol. 2012, 21, 45–51. [Google Scholar] [CrossRef] [PubMed]
- Su, B.-B. Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection. World J. Gastroenterol. 2012, 18, 2121–2126. [Google Scholar] [CrossRef]
- Bartel, D.P. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef]
- Catalanotto, C.; Cogoni, C.; Zardo, G. MicroRNA in Control of Gene Expression: An Overview of Nuclear Functions. Int. J. Mol. Sci. 2016, 17, 1712. [Google Scholar] [CrossRef]
- Aghdam, S.G.; Ebrazeh, M.; Hemmatzadeh, M.; Seyfizadeh, N.; Shabgah, A.G.; Azizi, G.; Ebrahimi, N.; Babaie, F.; Mohammadi, H. The role of microRNAs in prostate cancer migration, invasion, and metastasis. J. Cell. Physiol. 2018, 234, 9927–9942. [Google Scholar] [CrossRef]
- Smid, D.; Kulda, V.; Srbecka, K.; Kubackova, D.; Dolezal, J.; Daum, O.; Kucera, R.; Topolcan, O.; Treska, V.; Skalicky, T.; et al. Tissue microRNAs as predictive markers for gastric cancer patients undergoing palliative chemotherapy. Int. J. Oncol. 2016, 48, 2693–2703. [Google Scholar] [CrossRef]
- Pratap, P.; Raza, S.T.; Abbas, S.; Mahdi, F. MicroRNA-associated carcinogenesis in lung carcinoma. J. Cancer Res. Ther. 2018, 14, 249–254. [Google Scholar] [CrossRef]
- Pan, C.; Yan, X.; Li, H.; Huang, L.; Yin, M.; Yang, Y.; Gao, R.; Hong, L.; Ma, Y.; Shi, C.; et al. Systematic literature review and clinical validation of circulating microRNAs as diagnostic biomarkers for colorectal cancer. Oncotarget 2017, 8, 68317–68328. [Google Scholar] [CrossRef]
- O’Sullivan, A.; Henrick, B.; Dixon, B.; Barile, D.; Zivkovic, A.; Smilowitz, J.; Lemay, D.; Martin, W.; German, J.B.; Schaefer, S.E. 21st century toolkit for optimizing population health through precision nutrition. Crit. Rev. Food Sci. Nutr. 2017, 58, 3004–3015. [Google Scholar] [CrossRef]
- Horgan, D.; Čufer, T.; Gatto, F.; Lugowska, I.; Verbanac, D.; Carvalho, Â.; Lal, J.A.; Kozaric, M.; Toomey, S.; Ivanov, H.Y.; et al. Accelerating the Development and Validation of Liquid Biopsy for Early Cancer Screening and Treatment Tailoring. Healthcare 2022, 10, 1714. [Google Scholar] [CrossRef]
- Song, X.; Li, W.; Shen, P.; Bai, B.; Cao, L.-L. miR-19 Is a Potential Clinical Biomarker for Gastrointestinal Malignancy: A Systematic Review and Meta-analysis. BioMed Res. Int. 2020, 2020, 2810150. [Google Scholar] [CrossRef]
- Tsuchida, A.; Ohno, S.; Wu, W.; Borjigin, N.; Fujita, K.; Aoki, T.; Ueda, S.; Takanashi, M.; Kuroda, M. miR-92 is a key oncogenic component of the miR-17–92 cluster in colon cancer. Cancer Sci. 2011, 102, 2264–2271. [Google Scholar] [CrossRef]
- Lin, M.; Zhang, Z.; Gao, M.; Yu, H.; Sheng, H.; Huang, J. MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression. Cancer Manag. Res. 2019, 11, 5353–5363. [Google Scholar] [CrossRef] [PubMed]
- Pekow, J.; Meckel, K.; Dougherty, U.; Huang, Y.; Chen, X.; Almoghrabi, A.; Mustafi, R.; Ayaloglu-Butun, F.; Deng, Z.; Haider, H.I.; et al. MiR-193a-3p Is a Key Tumor Suppressor in Ulcerative Colitis-Associated Colon Cancer and Promotes Carcinogenesis through Upregulation of IL17RD. Clin. Cancer Res. 2017, 23, 5281–5291. [Google Scholar] [CrossRef] [PubMed]
- Tagscherer, K.E.; Fassl, A.; Sinkovic, T.; Richter, J.; Schecher, S.; Macher-Goeppinger, S.; Roth, W. MicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen. Cancer Cell Int. 2016, 16, 42. [Google Scholar] [CrossRef] [PubMed]
- Bavelloni, A.; Ramazzotti, G.; Poli, A.; Piazzi, M.; Focaccia, E.; Blalock, W.; Faenza, I. MiRNA-210: A Current Overview. Anticancer Res. 2017, 37, 6511–6521. [Google Scholar] [PubMed]
- Epidemiologija Raka Debelog Crijeva u Hrvatskoj|Hrvatski Zavod Za Javno Zdravstvo. Available online: https://www.hzjz.hr/sluzba-epidemiologija-prevencija-nezaraznih-bolesti/epidemiologija-raka-debelog-crijeva-u-hrvatskoj/ (accessed on 29 August 2022).
- Abo-Elela, D.A.; Salem, A.M.; Swellam, M.; Hegazy, M.G. Potential diagnostic role of circulating MiRNAs in colorectal cancer. Int. J. Immunopathol. Pharmacol. 2023, 37, 1–10. [Google Scholar] [CrossRef]
- About Colorectal Cancer. Available online: https://www.cancer.org/cancer/types/colon-rectal-cancer/about.html (accessed on 24 May 2024).
- Triantafillidis, J.K.; Vagianos, C.; Malgarinos, G. Colonoscopy in Colorectal Cancer Screening: Current Aspects. Indian J. Surg. Oncol. 2015, 6, 237–250. [Google Scholar] [CrossRef]
- Čvorišćec, D. TUMORSKI BILJEZI U KLINIČKOJ PRAKSI. HKMB, 2012. Available online: https://hkmb.hr/dokumenti/2012/Tumorski-biljezi-u-klin-praksi_HKMB.pdf (accessed on 24 May 2024).
- Jelski, W.; Mroczko, B. Biochemical Markers of Colorectal Cancer—Present and Future. Cancer Manag. Res. 2020, 12, 4789–4797. [Google Scholar] [CrossRef]
- dos Santos, I.L.; Penna, K.G.B.D.; Carneiro, M.A.d.S.; Libera, L.S.D.; Ramos, J.E.P.; Saddi, V.A. Tissue micro-RNAs associated with colorectal cancer prognosis: A systematic review. Mol. Biol. Rep. 2021, 48, 1853–1867. [Google Scholar] [CrossRef] [PubMed]
- Baumhoer, D.; Zillmer, S.; Unger, K.; Rosemann, M.; Atkinson, M.J.; Irmler, M.; Beckers, J.; Siggelkow, H.; von Luettichau, I.; Jundt, G.; et al. MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma. Cancer Genet. 2012, 205, 212–219. [Google Scholar] [CrossRef]
- Kozaki, K.-I.; Imoto, I.; Mogi, S.; Omura, K.; Inazawa, J. Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer. Cancer Res. 2008, 68, 2094–2105. [Google Scholar] [CrossRef]
- Benjamin, H.; Lebanony, D.; Rosenwald, S.; Cohen, L.; Gibori, H.; Barabash, N.; Ashkenazi, K.; Goren, E.; Meiri, E.; Morgenstern, S.; et al. A Diagnostic Assay Based on MicroRNA Expression Accurately Identifies Malignant Pleural Mesothelioma. J. Mol. Diagn. 2010, 12, 771–779. [Google Scholar] [CrossRef] [PubMed]
- Ma, T.; Li, H.; Yang, W.; Liu, Q.; Yan, H. Over-Expression of MiR-193a-3p Regulates the Apoptosis of Colorectal Cancer Cells by Targeting PAK3. Am. J. Transl. Res. 2022, 14, 1361–1375. [Google Scholar]
- Zhao, B.; Wang, W.; Ye, H.; Wang, J.; Meng, K.; Yang, T. A novel miRNA-based signature as predictive tool of survival outcome of colorectal cancer patients. Chem. Biol. Drug Des. 2023, 102, 1024–1033. [Google Scholar] [CrossRef] [PubMed]
- Mamoori, A.; Wahab, R.; Islam, F.; Lee, K.; Vider, J.; Lu, C.-T.; Gopalan, V.; Lam, A.K.-Y. Clinical and biological significance of miR-193a-3p targeted KRAS in colorectal cancer pathogenesis. Hum. Pathol. 2018, 71, 145–156. [Google Scholar] [CrossRef] [PubMed]
- Lin, M.; Duan, B.; Hu, J.; Yu, H.; Sheng, H.; Gao, H.; Huang, J. Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer. Oncol. Lett. 2017, 14, 1061–1067. [Google Scholar] [CrossRef] [PubMed]
- Motoyama, K.; Inoube, H.; Takatsuno, Y.; Tanaka, F.; Mimori, K.; Uetake, H.; Sugihara, K.; Mori, M. Over- and under-Expressed MicroRNAs in Human Colorectal Cancer. Int. J. Oncol. 2009, 34, 1069–1075. [Google Scholar] [CrossRef]
- Romanowicz, H.; Hogendorf, P.; Majos, A.; Durczyński, A.; Wojtasik, D.; Smolarz, B. Analysis of miR-143, miR-1, miR-210 and let-7e Expression in Colorectal Cancer in Relation to Histopathological Features. Genes 2022, 13, 875. [Google Scholar] [CrossRef] [PubMed]
- Ng, E.K.O.; Chong, W.W.S.; Jin, H.; Lam, E.K.Y.; Shin, V.Y.; Yu, J.; Poon, T.C.W.; Ng, S.S.M.; Sung, J.J.Y. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut 2009, 58, 1375–1381. [Google Scholar] [CrossRef]
- Vacante, M.; Ciuni, R.; Basile, F.; Biondi, A. The Liquid Biopsy in the Management of Colorectal Cancer: An Overview. Biomedicines 2020, 8, 308. [Google Scholar] [CrossRef]
- Dohmen, J.; Semaan, A.; Kobilay, M.; Zaleski, M.; Branchi, V.; Schlierf, A.; Hettwer, K.; Uhlig, S.; Hartmann, G.; Kalff, J.C.; et al. Diagnostic Potential of Exosomal microRNAs in Colorectal Cancer. Diagnostics 2022, 12, 1413. [Google Scholar] [CrossRef]
- Yong, F.L.; Law, C.W.; Wang, C.W. Potentiality of a triple microRNA classifier: miR-193a-3p, miR-23a and miR-338-5p for early detection of colorectal cancer. BMC Cancer 2013, 13, 280. [Google Scholar] [CrossRef]
- Pesta, M.; Kucera, R.; Topolcan, O.; Karlikova, M.; Houfkova, K.; Polivka, J.; Macanova, T.; Machova, I.; Slouka, D.; Kulda, V. Plasma microRNA Levels Combined with CEA and CA19-9 in the Follow-Up of Colorectal Cancer Patients. Cancers 2019, 11, 864. [Google Scholar] [CrossRef]
- Conev, N.V.; Donev, I.S.; Konsoulova-Kirova, A.A.; Chervenkov, T.G.; Kashlov, J.K.; Ivanov, K.D. Serum expression levels of miR-17, miR-21, and miR-92 as potential biomarkers for recurrence after adjuvant chemotherapy in colon cancer patients. Biosci. Trends 2015, 9, 393–401. [Google Scholar] [CrossRef]
- Li, G.; Wang, Q.; Li, Z.; Shen, Y. Serum miR-21 and miR-210 as promising non-invasive biomarkers for the diagnosis and prognosis of colorectal cancer. Rev. Esp. Enferm. Dig. 2020, 112, 832–837. [Google Scholar] [CrossRef]
- Zhou, T.; Zhang, G.; Liu, Z.; Xia, S.; Tian, H. Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer. Int. J. Color. Dis. 2012, 28, 19–24. [Google Scholar] [CrossRef]
- Li, Z.-w.; Yang, Y.-m.; Du, L.-t.; Dong, Z.; Wang, L.-l.; Zhang, X.; Zhou, X.-j.; Zheng, G.-x.; Qu, A.-l.; Wang, C.-x. Overexpression of MiR-223 Correlates with Tumor Metastasis and Poor Prognosis in Patients with Colorectal Cancer. Med. Oncol. 2014, 31, 256. [Google Scholar] [CrossRef]
- Vrdoljak, E.; Pleština, S.; Omrcen, T.; Juretic, A.; Lovasic, I.B.; Krznaric, Ž.; Flam, J.; Šobat, H.; Šeparovic, R.; Bo-lanca, A.; et al. Clinical Guidelines for Diagnosis, Treatment and Monitoring Patients with Colorectal Cancer. Lijec. Vjesn. 2018, 140, 241–247. [Google Scholar]
- Demirović, A.; Krušlin, B. Recommendations for histopathology report of colorectal carcinoma specimens. Rad. Hrvat. Akad. Znan. Umjet. 2017, 530, 67–72. [Google Scholar] [CrossRef]
- Jakić-Razumović, J. Protocol for the primary colon and rectum carcinoma specimen examination. Med. Sci. 2015, 41, 117–130. [Google Scholar]
Parameter | pre-CRC Controls (n = 76) | CRC Patients (n = 52) | p-Value |
---|---|---|---|
Age | 67 (32–84) | 72 (37–90) | 0.0019 |
CA 19-9 (kIU/L) | 5.81 (2.59–11.72) * | 9.03 (6.70–18.95) ** | <0.0001 |
CEA (μg/L) | 1.73 (1.23–2.67) * | 3.50 (2.41–7.55) *** | <0.0001 |
Pathohistological Parameter | Pathohistological Subcategory | % of CRC Patients |
---|---|---|
MSI | MSS | 82.5 |
MSI-H | 17.5 | |
pTMN stage | 1 | 30 |
2 | 32 | |
3 | 32 | |
4 | 6 | |
gradus | Low | 95.8 |
high | 4.2 | |
subtype | NOS | 98 |
mucinous | 2 | |
tumor size in cm | ≤2 | 12 |
>2 ≤ 5 | 68 | |
>5 ≤ 10 | 20 |
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Fabijanec, M.; Hulina-Tomašković, A.; Štefanović, M.; Verbanac, D.; Ćelap, I.; Somborac-Bačura, A.; Grdić Rajković, M.; Demirović, A.; Ramić, S.; Krušlin, B.; et al. MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients. Int. J. Mol. Sci. 2024, 25, 8156. https://doi.org/10.3390/ijms25158156
Fabijanec M, Hulina-Tomašković A, Štefanović M, Verbanac D, Ćelap I, Somborac-Bačura A, Grdić Rajković M, Demirović A, Ramić S, Krušlin B, et al. MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients. International Journal of Molecular Sciences. 2024; 25(15):8156. https://doi.org/10.3390/ijms25158156
Chicago/Turabian StyleFabijanec, Marija, Andrea Hulina-Tomašković, Mario Štefanović, Donatella Verbanac, Ivana Ćelap, Anita Somborac-Bačura, Marija Grdić Rajković, Alma Demirović, Snježana Ramić, Božo Krušlin, and et al. 2024. "MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients" International Journal of Molecular Sciences 25, no. 15: 8156. https://doi.org/10.3390/ijms25158156