Analysis of expression of m 6A regulators in colorectal tumor samples based on TCGA and GEO databases / 中国基层医药

ABSTRACT

Objective:To detect the expression of N6-methyladenosine (m 6A) regulators in colorectal tumor samples and its clinical significance. Methods:From September to December 2021, the data regarding the expression of m 6A regulators in colorectal tumor samples were collected using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and the expression of m 6A regulators was compared between different clinical pathological characteristics and between different molecular subtypes. Survival analysis was conducted in patients with colorectal cancer with different m 6A expression levels. Results:In TCGA, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) were higher in colorectal tumor samples than normal tissue samples (TCGA-COAD IGF2BP3 12.80 vs. 204.46, logFC = 4.00, P = 0.003; YTHDF1 2 347.56 vs. 3712.77, logFC = 0.66, P < 0.001; TCGA-READ IGF2BP1 6.20 vs. 359.32, logFC = 5.82, P = 0.007; YTHDF1 2 470.10 vs. 4 369.09, logFC = 0.82, P = 0.020). The intersection of TCGA and GEO databases showed that methyltransferase like 14 (METTL14), YTH domain m 6A RNA binding protein 3 (YTHDF3), and α-ketoglutarate dependent dioxygenase AlkB homolog 5 (ALKBH5) were downregulated in colorectal tumor samples compared with normal tissue samples (TCGA-COAD METTL14 1 051.56 vs. 711.40, logFC = -0.56, P < 0.001; YTHDF34 613.85 vs. 3 155.05, logFC = -0.55, P < 0.001, ALKBH5 4 250.10 vs. 2 555.55, logFC = -0.73, P < 0.001; TCGA-READ vs. METTL14 1 113.3 vs. 674.36, logFC = -0.72, P < 0.001; YTHDF3 5 034.30 vs. 3 331.95, logFC = -0.60, P = 0.004; ALKBH5 4 902.20 vs. 2 529.71, logFC = -0.95, P < 0.001; GEO-CRC vs. METTL14 6.58 vs. 6.33, logFC = -0.06, P < 0.001; YTHDF3 6.28 vs. 6.20, logFC = -0.02, P = 0.002; ALKBH5 5.07 vs. 4.98, logFC = -0.02, P < 0.001). In colorectal tumor samples of different molecular subtypes, IGF2BP2, HNRNPC, TP53 and YTHDF2 expression was low in KRAS (IGF2BP2 48.53 vs. 44.04, t = 2.64, P = 0.008; HNRNPC 121.30 vs. 112.60, t = 2.32, P = 0.020; TP53 65.30 vs. 60.26, t = 2.11, P = 0.034; YTHDF2 54.07 vs. 51.19; t = 1.97, P = 0.048). Different clinical pathological characteristics showed that IGF2BP1 was higher in colorectal cancer with positive lymph nodes (8.97 vs. 6.11, W = 20 008, P = 0.002), distant metastasis (8.94 vs. 6.41, W = 19 104, P = 0.009), or stage Ⅲ-Ⅳ (7.46 vs. 7.13, W = 8 779, P = 0.025) than normal tissue. ALKBH5 overexpression, advanced age, presence of vascular invasion, and late pathological staging were significantly related to a short survival period (high ALKBH5 expression vs. low ALKBH5 expression 5.85 years vs. not available, HR 1.63, 95% CI 1.071-2.491, P = 0.021; > 68 years vs. < 68 years 6.78 years vs. not available, HR 1.59, 95% CI 1.049-2.422, P = 0.047; stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ 4.55 years vs. 8.33 years, HR 2.89, 95% CI 1.895-4.425, P < 0.001; presence of vein invasion vs. absence of vein invasion 5.48 years vs. not available, HR 2.82, 95% CI 1.672-4.783, P < 0.001). Conclusion:Some of the m 6A regulators are associated with the biological characteristics and prognosis of colorectal cancer.