Comprehensive Analysis of N6-Methyladenosine-Related lncRNA Signature for Predicting Prognosis and Immune Cell Infiltration in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group (P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs. The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.

Zhao Z ，Yang YB ，Li XY ，Li XG ，Chu XD ，Lin ZB ，Zhang YR ，Guo YG ，Ding H ，Pan YL ，Wang L ，Pan JH ... -  《-》

N6-Methyladenosine-Related lncRNA Signature Predicts the Overall Survival of Colorectal Cancer Patients.

Song W ，Ren J ，Yuan W ，Xiang R ，Ge Y ，Fu T ... -  《Genes》

Construction of an N6-methyladenosine lncRNA- and immune cell infiltration-related prognostic model in colorectal cancer.

Yu ZL ，Zhu ZM 《-》

Analysis of N6-methyladenosine-related lncRNAs in the tumor immune microenvironment and their prognostic role in pancreatic cancer.

Pancreatic cancer (PC) is a rare solid malignancy with a poor prognosis. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and progression. However, little is known about the role of m6A-related lncRNAs in PC. m6A-related lncRNAs were extracted by Pearson analysis, and then prognosis-related lncRNAs were filtered from the m6A-related lncRNAs by univariate Cox regression analysis. Based on the expression patterns of the prognosis-related lncRNAs, samples were classified into distinct clusters. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct a m6A-lncRNA-related prognostic signature for PC patients. Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) values were used to evaluate the prognostic ability of the model. A total of 178 tumor and 4 normal samples were extracted from The Cancer Genome Atlas (TCGA) database in our study. Based on the expression of 12 filtered prognosis-related lncRNAs, two distinct clusters were eventually identified; these clusters were characterized by differences in the tumor immune microenvironment (TIME) and prognosis. A risk model comprising ten m6A-related lncRNAs was identified as an independent predictor of prognosis. ROC analysis revealed that this model had an acceptable prognostic value for PC patients. The prognostic signature was related to the TIME and the expression of critical immune checkpoint molecules. This study comprehensively assessed the expression pattern and prognostic value of m6A-related lncRNAs in PC. The different clusters correlated with distinct TIMEs and prognoses. The study also constructed a ten-gene signature prognostic model based on m6A-related lncRNAs, which showed good accuracy in predicting overall survival.

Liu Y ，Wang T ，Fang Z ，Kong J ，Liu J ... -  《-》

N6-methyladenosine-related lncRNAs identified as potential biomarkers for predicting the overall survival of Asian gastric cancer patients.

Gastric cancer (GC) is one of the most prevalent malignant tumors in Asian countries. Studies have proposed that lncRNAs can be used as diagnostic and prognostic indicators of GC due to the high specificity of lncRNAs expression involvement in GC. Recently, N6-methyladenosine (m6A) has also emerged as an important modulator of the expression of lncRNAs in GC. This study aimed at establishing a novel m6A-related lncRNAs prognostic signature that can be used to construct accurate models for predicting the prognosis of GC in the Asian population. First, the levels of m6A modification and m6A methyltransferases expression in GC samples were determined using dot blot and western blot analyses. Next, we evaluated the lncRNAs expression profiles and the corresponding clinical data of 88 Asian GC patients retrieved from The Cancer Genome Atlas (TCGA) database. Differential expression of m6A-related lncRNAs between GC and normal tissues was investigated. The relationship between these target lncRNAs and potential immunotherapeutic signatures was also analyzed. Gene set enrichment analysis (GSEA) was performed to identify the malignancy-associated pathways. Univariate Cox regression, LASSO regression, and multivariate Cox regression analyses were performed to establish a novel prognostic m6A-related lncRNAs prognostic signature. Moreover, we constructed a predictive nomogram and determined the expression levels of nine m6A-related lncRNAs in 12 pairs of clinical samples. We found that m6A methylation levels were significantly increased in GC tumor samples compared to adjacent normal tissues, and the increase was positively correlated with tumor stage. Patients were then divided into two clusters (cluster 1 and cluster 2) based on the differential expression of the m6A-related lncRNAs. Results showed that there was a significant difference in survival probability between the two clusters (p = 0.018). Notably, the low survival rate in cluster 2 may be associated with high expression of immune cells (resting memory CD4+ T cells, p = 0.027; regulatory T cells, p = 0.0018; monocytes, p = 0.00095; and resting dendritic cells, p = 0.015), and low expression of immune cells (resting NK cells, p = 0.033; and macrophages M1, p = 0.045). Enrichment analysis indicated that malignancy-associated biological processes were more common in the cluster 2 subgroup. Finally, the risk model comprising of six m6A-related lncRNAs was identified as an independent predictor of prognoses, which could divide patients into high- or low-risk groups. Time-dependent ROC analysis suggested that the risk score could accurately predict the prognosis of GC patients. Patients in the high-risk group had worse outcomes compared to patients in the low-risk group, and the risk score showed a positive correlation with immune cells (resting memory CD4+ T cells, R = 0.31, P = 0.038; regulatory T cells, R = 0.42, P = 0.0042; monocytes, R = 0.42, P = 0.0043). However, M1 macrophages (R = -0.37, P = 0.012) and resting NK cells (R = -0.31, P = 0.043) had a negative correlation with risk scores. Furthermore, analysis of clinical samples validated the weak positive correlation between the risk score and tumor stage. The risk model described here, based on the six m6A-related lncRNAs signature, and may predict the clinical prognoses and immunotherapeutic response in Asian GC patients.

Xu S ，Chen W ，Wang Y ，Zhang Y ，Xia R ，Shen J ，Gong X ，Liang Y ，Xu J ，Tang H ，Zhao T ，Zhang Y ，Chen T ，Wang C ... -  《BMC CANCER》