Dataset Information

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

ABSTRACT:

Background

N6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A "eraser", FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC.

Materials and methods

A total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into training set and testing set. Differential expression analysis of the m6A "eraser" related genes was performed. The LASSO Cox regression model was constructed to analyze the m6A "eraser" related risk genes. The univariate and multivariate Cox regression model were employed to identify the independent prognostic factors. Kaplan-Meier method was used for survival analysis. A nomogram model was then carried out to predict the prognosis of GC patients. Additionally, GO and KEGG analyses were conducted to identify the potential role of the m6A "eraser" related genes in GC. The relative proportion of 22 different genotypes in immune infiltrating cells was calculated by CIBERSORT algorithm.

Results

In total, nine m6A "eraser" related risk genes and risk scores were obtained and calculated. Patients in high-risk group demonstrated significantly worse prognosis than those in low-risk group. Age, stage, and risk score were considered as independent prognostic factors. The nomogram model constructed accurately predicted the 3-year and 5-year overall survival (OS) of patients. Furthermore, m6A "eraser" might play a functional role in GC. The expression of m6A "eraser" leads to changes in tumor immune microenvironment.

Conclusions

FTO and ALKBH5 showed association with the prognosis of GC. The m6A "eraser" related genes, which is considered as a reliable prognostic and predictive tool, assists in predicting the OS in GC patients.

SUBMITTER: Xu X

PROVIDER: S-EPMC7952866 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

Xu Xin X Zhou En E Zheng Jun J Zhang Chihao C Zou Yinghua Y Lin Jiayun J Yu Jiwei J

Frontiers in oncology 20210226

<h4>Background</h4>N6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A "eraser", FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC.<h4>Materials and methods</h4>A total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into traini ...[more]

PMID: 33718213

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Project description:Purpose: Gastric cancer (GC) is a primary cause of cancer-associated mortality worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications that involves in the progression of numerous cancers. However, the expression status and function of m6A-related genes in gastric cancer is still not well understood. The current study is aimed to investigate the expression status and determinate prognostic value of m6A-related genes in gastric cancer. Methods: m6A-asssociated gene expression was evaluated via analyzing the expression data of GC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The protein expression levels of m6A-associated molecules were further validated by immunohistochemical (IHC) staining data from GC tissue microarray (TMA) cohort and Human Protein Atlas (HPA) database. Kaplan-Meier analysis was performed to assess the prognostic value of m6A-associated genes in gastric cancer. Risk score model was established by lasso COX regression analysis and its prognostic predicted efficiency was assessed by the receiver-operator characteristic (ROC) curve. Cox regression analyses were used for exploring risk factors related to GC patient prognosis. Results: Most of m6A-related genes were upregulated at both mRNA and protein levels in gastric cancer tissues compared with that in normal gastric tissues. The expression levels of m6A-related genes were associated with clinicopathological features including race, age and TNM stage. High expression of WTAP and FTO predicted poor prognosis of GC patients. Survival analysis demonstrated that patients with high-risk scores had worse overall survival (OS) and ROC curves suggested the prediction performance for gastric patients. Moreover, Cox regression analyses indicated that m6A risk model score was a prognostic factor for OS and FTO upregulation might be a potential independent prognostic factor for recurrence-free survival (RFS) in gastric cancer patients. Conclusion: m6A-related genes were dysregulated in GC and were closely associated with prognosis of GC patients. FTO might serve as a novel prognostic biomarker for gastric cancer, while the m6A-related risk score might be informative for risk assessment and prognostic stratification.

Project description:BackgroundAutophagy is associated with cancer development. Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. Here we evaluated the value of a prognostic signature based on autophagy-related genes for EC.MethodsFirst, various autophagy-related genes were obtained via the Human Autophagy Database and their expression profiles were downloaded from The Cancer Genome Atlas. Second, key prognostic autophagy-related genes were identified via univariate, LASSO and multivariate Cox regression analyses. Finally, a risk score to predict the prognosis of EC was calculated and validated by using the test and the entire data sets. Besides, the key genes mRNA expression were validated using quantitative real-time PCR in clinical tissue samples.ResultsA total of 40 differentially expressed autophagy-related genes in EC were screened and five of them were prognosis-related (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1). A prognostic signature was constructed based on these five genes using the train set, which stratified EC patients into high-risk and low-risk groups (p < 0.05). In terms of overall survival, the analyses of the test set and the entire set yielded consistent results (test set: p < 0.05; entire set: p < 0.05). Time-dependent ROC analysis suggested that the risk score predicted EC prognosis accurately and independently (0.674 at 1 year, 0.712 at 3 years and 0.659 at 5 years). A nomogram with clinical utility was built. Patients in the high-risk group displayed distinct mutation signatures compared with those in the low-risk group. For clinical sample validation, we found that EIF4EBP1and ERBB2 had higher level in EC than that in normal tissues while CDKN1B, DLC1 and GRID1 had lower level, which was consistent with the results predicted.ConclusionsBased on five autophagy-related genes (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1), our model can independently predict the OS of EC patients by combining molecular signature and clinical characteristics.

Dataset Information

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

Background

Materials and methods

Results

Conclusions

Publications

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

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