A pan‐cancer analysis reveals genetic alterations, molecular mechanisms, and clinical relevance of m 5 C regulators

Abstract

5 C regulators in pan-cancer. A, The writers, readers, and erasers diagram of m 5 C regulators. B, The gene expression alterations of m 5 C regulators across 23 cancer types selected from the TCGA database, fold changes are shown by a heat map, the upregulated genes are represented as red, and downregulated genes are represented as blue. C, The box diagrams showing NSUN1 expression across 17 cancer types from the TCGA database, and t-test was used to calculate the significance level of differences by comparing tumor groups with normal groups. * P-value < .05; **P-value < .01; ***P-value < .001; ****P-value < .0001. D, The mutation frequency across 33 cancer types. The x axis indicates cancer types and y axis indicates m 5 C regulators. E, The CNV gain and loss frequency across 33 cancer types. The CNV gain frequency is colored by dark red; the CNV loss frequency is colored by midnight-blue. The x-axis indicates cancer types, and the y-axis indicates m 5 C regulators. F, Correlation between CNV and mRNA expression across 33 cancer types from TCGA database. The point diagram is depicted to show the relationship, the size of a point is represented the P-value, the correlation coefficient was colored by red; the greater the correlation, the deeper the red. The x-axis indicates cancer types, and y-axis indicates m 5 C regulators that they might be affected by each other (Figure 2C and D; Table S9). We further excavated the regulators-prognosis correlation utilizing the TCGA clinical data. We found that at least one regulator was correlated with the patients' prognosis in 22 cancers (Figure 3A). Intriguingly, we observed that NSUN1 represented high hazard ratios in many cancers, and patients with high NSUN1 expression showed poorer survival probabilities across nine cancers (Figures S7 and S8). Other regulators, NSUN2, NSUN5, and ALYREF, also showed high hazard ratios in several cancers. Noticeably, YBX1 had a slight expression alteration but still represented high hazard ratios in many cancers (Table S10). Moreover, more regulators were related to the prognosis of KIRC, LIHC, ACC, and LGG patients. In KIRC, some regulators (NSUN1, NSUN2, NSUN5, NSUN6, ALYREF, and YBX1) showed risky functions, and others showed protective functions (Figure S9A). However, almost all regulators acted as an oncogene in LIHC, LGG, and ACC (Figure S9B and C).