Abstract
Background Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). Results The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. Conclusion Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.
Highlights
Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system, causing approximately 350,000 deaths worldwide every year [1]
Within the The Cancer Genome Atlas (TCGA) database, only 19 independent samples were found to have mutations of m6A regulatory genes (Table 1), among the 186 cases based on the sequencing data; copy number variation (CNV) in ten m6A-related genes were observed in 177 pancreatic adenocarcinoma (PAAD) samples based on the CNV data (Figure 1(a))
The results showed that the m6A “writer” gene WTAP had the highest frequency of CNV events (50.8%, 90/177) followed by ALKBH5 (48.02%, 85/177), which is an m6A “eraser” gene
Summary
Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), is one of the most malignant tumors of the digestive system, causing approximately 350,000 deaths worldwide every year [1]. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. We obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Our study demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis and provided a novel therapeutic target for pancreatic cancer therapy
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