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. 2023 Aug 15:16:3517-3531.
doi: 10.2147/IJGM.S420127. eCollection 2023.

MALAT1 in Liquid Biopsy: The Diagnostic and Prognostic Promise for Colorectal Cancer and Adenomas?

Klara Cervena  1   2 , Anna Siskova  1   2 , Jiri Jungwirth  3   4 , Marin Volarić  5 , Jan Kral  6 , Pavel Kohout  7 , Miroslav Levy  8 , Veronika Vymetalkova  1   2   9
Affiliations

MALAT1 in Liquid Biopsy: The Diagnostic and Prognostic Promise for Colorectal Cancer and Adenomas?

Klara Cervena et al. Int J Gen Med. .

Abstract

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.

Keywords: MALAT1; colorectal adenomas; colorectal cancer; liquid biopsy; plasma.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic workflow of the study. RT-qPCR analysis of MALAT1 was performed in the tumour tissue and adjacent mucosa of CA patients (n=14) who were part of the pilot study and further in the plasma of CFI (n=48), CA patients (n=97) and CRC patients (n=101).
Figure 2
Figure 2
The expression levels of MALAT1 in the tissue of CA patients from the pilot phase. No significant difference was observed between the groups with and without MALAT1 amplification (p=0.08, 2.08-fold-change).
Figure 3
Figure 3
The expression level of MALAT1 in plasma. There are significant differences between CA and CRC patients compared to CFI (CA vs CFI – p<0.001, 5.25- fold change; CRC vs CFI – p<0.001, 5.16-fold change). The asterisk indicator (***) represents p ≤ 0.001.
Figure 4
Figure 4
The expression level of MALAT1 in different types of adenomas. There was a significant difference between hyperplastic (H; n=9) and tubulovillous/villous (TLV; n=30) adenomas (p=0.002, 6.14-fold change). Tubular (T; n=50) adenomas did not show a significant difference in MALAT1 expression (p=0.15, 3.09-fold change). The asterisk indicator (**) represents p ≤ 0.01.
Figure 5
Figure 5
The expression level of MALAT1 in CRC patients divided according to therapy response. There was a significant difference between good (n=52) and poor responders (n=42; p=0.04, 1.86-fold change). The asterisk indicator (*) represents p ≤ 0.05.
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