INTRODUCTION: The development of colorectal cancer (CRC) is a multistep process accompanied by the accumulation of mutations that start from specific precancerous lesion - colorectal adenomas (CA). CRC incidence and mortality can be reduced by the early identification of these neoplasm. Colonoscopy is the most widely used screening method for CRC identification. Nowadays, clinical research interest is shifting to the use of liquid biopsy that may help with the early diagnosis of CA and CRC. In our previous study, we identified long non-coding RNA MALAT1 gene amplification associated with the development of CA. METHODS: This study aimed to describe the potential of MALAT1 expression levels in the adenoma tissue of patients used in the previous study by real-time qPCR. Furthermore, we analysed the plasma samples of an independent group of patients with CA (n=97), CRC (n=101), and cancer-free individuals (CFI, n=48). RESULTS: There was no difference in the MALAT1 expression level between CA patients with or without MALAT1 amplification. However, the plasma MALAT1 expression levels were significantly upregulated in patients with CRC and CA compared to CFI (for both p<0.001). Moreover, a correlation between MALAT1 expression and histological types of adenomas was identified- high-CRC-risk adenomas also displayed the highest MALAT1 expression levels. Furthermore, in CRC patients, MALAT1 levels were associated with a response to therapy. CONCLUSION: MALAT1 expression levels could serve as a promising circulating biomarker for early CA and CRC diagnosis, and even as a predictor of therapy response in CRC patients.

Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Pilsen 323 00 Czech Republic

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Prague 140 21 Czech Republic

Department of Internal Medicine 3rd Faculty of Medicine Charles University and Faculty Thomayer Hospital Prague Prague 140 00 Czech Republic

Department of Surgery 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Prague 140 59 Czech Republic

Department of Surgery Weiden Clinic Weiden in der Oberpfalz 92637 Germany

Institute of Biology and Medical Genetics 1st Medical Faculty Charles University Prague 128 00 Czech Republic

Institute of Experimental Medicine Czech Academy of Sciences Prague 142 00 Czech Republic

Institute of Physiology 1st Faculty of Medicine Charles University Prague 121 08 Czech Republic

Laboratory for Non Coding DNA Ruđer Bošković Institute Zagreb 10000 Croatia

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Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. PubMed DOI

Siskova A, Cervena K, Kral J, et al. Colorectal Adenomas-Genetics and Searching for New Molecular Screening Biomarkers. PubMed DOI PMC

Rubio CA, Jaramillo E, Lindblom A, et al. Classification of colorectal polyps: guidelines for the endoscopist. PubMed DOI

Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. PubMed DOI

Allescher HD, Weingart V. Optimizing Screening Colonoscopy: strategies and Alternatives. PubMed DOI PMC

Kim SY, Kim HS, Park HJ. Adverse events related to colonoscopy: global trends and future challenges. PubMed DOI PMC

Gonzalez-Kozlova EE. Molecular Profiling of Liquid Biopsies for Precision Oncology. PubMed

Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic - implementation issues and future challenges. PubMed DOI

Lone SN, Nisar S, Masoodi T, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. PubMed DOI PMC

Cervena K, Pardini B, Urbanova M, et al. Mutational landscape of plasma cell-free DNA identifies molecular features associated with therapeutic response in patients with colon cancer. A pilot study. PubMed DOI

Suraj S, Dhar C, Srivastava S. Circulating nucleic acids: an analysis of their occurrence in malignancies. PubMed DOI PMC

Szilagyi M, Pös O, Márton É, et al. Circulating Cell-Free Nucleic Acids: main Characteristics and Clinical Application. PubMed DOI PMC

Brannan CI, Dees EC, Ingram RS, et al. The product of the H19 gene may function as an RNA. PubMed DOI PMC

Kosinska-Selbi B, Mielczarek M, Szyda J. Review: long non-coding RNA in livestock. PubMed DOI

Cervena K, Vodenkova S, Vymetalkova V. MALAT1 in colorectal cancer: its implication as a diagnostic, prognostic, and predictive biomarker. PubMed DOI

Siskova A, Kral J, Drabova J, et al. Discovery of Long Non-Coding RNA MALAT1 Amplification in Precancerous Colorectal Lesions. PubMed DOI PMC

Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. PubMed DOI

Chaleshi V, Irani S, Alebouyeh M, et al. Association of lncRNA-p53 regulatory network (lincRNA-p21, lincRNA-ROR and MALAT1) and p53 with the clinicopathological features of colorectal primary lesions and tumors. PubMed DOI PMC

Xu Y, Zhang X, Hu X, et al. The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. PubMed DOI PMC

Schlemper RJ, Riddell RH, Kato YE, et al. The Vienna classification of gastrointestinal epithelial neoplasia. PubMed DOI PMC

Li JH, Liu S, Zhou H, et al. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. PubMed DOI PMC

Li J, Ma W, Zeng P, et al. LncTar: a tool for predicting the RNA targets of long noncoding RNAs. PubMed DOI

Mi H, Thomas P. PANTHER pathway: an ontology-based pathway database coupled with data analysis tools. PubMed PMC

He J, Wu F, Han Z, et al. Biomarkers (mRNAs and Non-Coding RNAs) for the Diagnosis and Prognosis of Colorectal Cancer - From the Body Fluid to Tissue Level. PubMed DOI PMC

Okugawa Y, Toiyama Y, Hur K, et al. Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. PubMed DOI PMC

Pang EJ, Yang R, Fu X-B, et al. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. PubMed DOI

Yue X, Wu W-Y, Dong M, et al. LncRNA MALAT1 promotes breast cancer progression and doxorubicin resistance via regulating miR-570-3p. PubMed DOI PMC

Arun G, Aggarwal D, Spector DL. MALAT1 Long Non-Coding RNA: functional Implications. PubMed DOI PMC

Tripathi V, Ellis JD, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. PubMed DOI PMC

Yang L, Lin C, Liu W, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. PubMed DOI PMC

Su X, Xing J, Wang Z, et al. microRNAs and ceRNAs: RNA networks in pathogenesis of cancer. PubMed DOI PMC

Tang Y, Xiao G, Chen Y, et al. LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling. PubMed DOI

Xie JJ, Li WH, Li X, et al. LncRNA MALAT1 promotes colorectal cancer development by sponging miR-363-3p to regulate EZH2 expression. PubMed

Guo J, Ding Y, Yang H, et al. Aberrant expression of lncRNA MALAT1 modulates radioresistance in colorectal cancer in vitro via miR-101-3p sponging. PubMed DOI

Ji Q, Cai G, Liu X, et al. MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 in colorectal cancer metastasis. PubMed DOI PMC

Liu Y, Yin Z, Lu P, et al. Lung Carcinoma Cells Secrete Exosomal MALAT1 to Inhibit Dendritic Cell Phagocytosis, Inflammatory Response, Costimulatory Molecule Expression and Promote Dendritic Cell Autophagy via AKT/mTOR Pathway. PubMed DOI PMC

Hewitson JP, West KA, James KR, et al. Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells. PubMed DOI PMC

Zhao G, Su Z, Song D, et al. The long noncoding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-kappaB. PubMed DOI

Wang QM, Lian G-Y, Song Y, et al. LncRNA MALAT1 promotes tumorigenesis and immune escape of diffuse large B cell lymphoma by sponging miR-195. PubMed DOI

Sun Z, Ou C, Liu J, et al. YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer. PubMed DOI PMC

Matheu A, Collado M, Wise C, et al. Oncogenicity of the developmental transcription factor Sox9. PubMed DOI PMC

Lu B, Fang Y, Xu J, et al. Analysis of SOX9 expression in colorectal cancer. PubMed DOI

Lizarraga-Verdugo E, Carmona T, Ramos-Payan R, et al. SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients. PubMed DOI PMC

Szulzewsky F, Holland EC, Vasioukhin V. YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance. PubMed DOI PMC

Jass JR. Gastrointestinal polyposes: clinical, pathological and molecular features. PubMed DOI

Zheng HT, Shi D-B, Wang Y-W, et al. High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. PubMed PMC

Wu X, Li R, Song Q, et al. JMJD2C promotes colorectal cancer metastasis via regulating histone methylation of MALAT1 promoter and enhancing beta-catenin signaling pathway. PubMed DOI PMC

Li Q, Dai Y, Wang F, et al. Differentially expressed long non-coding RNAs and the prognostic potential in colorectal cancer. PubMed DOI

Li P, Zhang X, Wang H, et al. MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2. PubMed DOI

Fan C, Yuan Q, Liu G, et al. Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells. PubMed DOI PMC

Kyula JN, Van Schaeybroeck S, Doherty J, et al. Chemotherapy-induced activation of ADAM-17: a novel mechanism of drug resistance in colorectal cancer. PubMed DOI PMC

Siddique H, Al-Ghafari A, Choudhry H, et al. Long Noncoding RNAs as Prognostic Markers for Colorectal Cancer in Saudi Patients. PubMed DOI

Radwan AF, Shaker OG, El-Boghdady NA, et al. Association of MALAT1 and PVT1 Variants, Expression Profiles and Target miRNA-101 and miRNA-186 with Colorectal Cancer: correlation with Epithelial-Mesenchymal Transition. PubMed DOI PMC

Li Y, Bao C, Gu S, et al. Associations between novel genetic variants in the promoter region of MALAT1 and risk of colorectal cancer. PubMed DOI PMC

Zhao K, Jin S, Wei B, et al. Association study of genetic variation of lncRNA MALAT1 with carcinogenesis of colorectal cancer. PubMed DOI PMC

Yang Q, Zheng W, Shen Z, et al. MicroRNA Binding Site Polymorphisms of the Long-Chain Noncoding RNA MALAT1 are Associated with Risk and Prognosis of Colorectal Cancer in Chinese Han Population. PubMed DOI

Wu S, Sun H, Wang Y, et al. MALAT1 rs664589 Polymorphism Inhibits Binding to miR-194-5p, Contributing to Colorectal Cancer Risk, Growth, and Metastasis. PubMed DOI