Abstract
Effective biomarkers for the diagnosis of colorectal cancer (CRC) are essential for improving prognosis. Imbalance in regulation of N6-methyladenosine (m6A) RNA has been associated with a variety of cancers. However, whether the m6A RNA levels of peripheral blood can serve as a diagnostic biomarker for CRC is still unclear. In this research, we found that the m6A RNA levels of peripheral blood immune cells were apparently elevated in the CRC group compared with those in the normal controls (NCs) group. Furthermore, the m6A levels arose as CRC progressed and metastasized, while these levels decreased after treatment. The area under the curve (AUC) of the m6A levels was 0.946, which was significantly higher than the AUCs for carcinoembryonic antigen (CEA; 0.817), carbohydrate antigen 125 (CA125; 0.732), and carbohydrate antigen 19-9 (CA19-9; 0.771). Moreover, the combination of CEA, CA125, and CA19-9 with m6A levels improved the AUC to 0.977. Bioinformatics and qRT-PCR analysis further confirmed that the expression of m6A modifying regulator IGF2BP2 was markedly elevated in peripheral blood of CRC patients. Gene set variation analysis (GSVA) implied that monocyte was the most abundant m6A-modified immune cell type in CRC patients’ peripheral blood. Additionally, m6A modifications were negatively related to the immune response of monocytes. In conclusion, our results revealed that m6A RNA of peripheral blood immune cells was a prospective non-invasive diagnostic biomarker for CRC patients and might provide a valuable therapeutic target.
Highlights
Colorectal cancer (CRC) is a common malignancy and the fourth leading cause of cancer-related deaths globally [1]
Our data indicated that the m6A levels correlated with M classification (p < 0.001), but not with clinical stage, T classification, N classification, differentiation, tumor budding, as well as other common colorectal cancer (CRC) tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), and carbohydrate antigen 19-9 (CA19-9) (Table 1)
CRC patients with distant tumor metastasis (n = 26, 0.302 ± 0.063) had apparently increased m6A levels compared to those without distant metastasis (n = 57, 0.259 ± 0.041; Figure 1C). These results suggested that peripheral blood m6A RNA levels could partially distinguish the various pathological stages in patients with CRC
Summary
Colorectal cancer (CRC) is a common malignancy and the fourth leading cause of cancer-related deaths globally [1]. If diagnosed in the early stage, the 5-year survival rate of CRC patients is as high as 70%–90% [2]. CRC patients with tumor metastases present a worse prognosis, with a 5-year survival rate of only approximately 20% [3]. The identification of blood biomarkers has become an important issue because of the pain-free operation of blood biomarkers testing [6]. Blood biomarkers such as carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) are broadly applied for CRC detection [7, 8]. There is an urgent need to optimize the diagnosis of CRC by other efficient blood biomarkers
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