Integrative Analysis of the AMPK subunits in Colorectal Adeno Carcinoma

Abstract

Background: The 5-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an emerging cancer treatment and therapeutic target. Due to the enzyme's complexity and dual nature, it is a confounding target in the treatment strategy. The study aimed to conduct an integrative analysis of the seven subunits and twelve isoforms of AMPK, which is not reported so far in colorectal adenocarcinoma patients.

Methodology: The web-based tools UALCAN, Timer 2.0, KM Plotter, cBioPortal, COSMIC, and STRING were used to investigate the differential expression of AMPK subunits, protein-level Expression, promoter methylation status, survival analyses, Enrichment analysis, and protein-protein interaction.

Results: The mRNA expression of AMPK subunits are upregulated in Colorectal Adeno Carcinoma (COAD), while the protein expression is comparatively reduced in colon tumors. The protein-level expression of α2 and β2 is decreased significantly in COAD patients. The γ3 subunit in colon tumor is hypermethylated. The study also reports that Liver Kinase B1 mutation in 7% of CRC patients, which might be the reason for downregulation of the gene and the protein expression of AMPK subunits in COAD.

Conclusion: The Overall analysis of the subunits affirms that AMPK expression is beneficial in cancer.

Keywords: AMPK; Protein expression; Survival Analysis; colorectal cancer; differential gene expression.

Figure 1

(A), The Types of Colorectal cancer; (B), The pattern of differentiation; (C), Overall Survival (OS) status of patients; (D), KM plots of progression-free survival; and OS (E) of 471 patients from TCGA datasets of cBioPortal

Figure 2

The Pie Diagram Showing the Metastasis Pattern of the 471 Colorectal Cancer Patients from TCGA Datasets

Figure 3

The PAN CANCER Analysis of AMPK Subunits (A-C) in Normal and Colon Tumors across the TCGA Datasets. The p- values are also represented as stars

Figure 4

The Differential Expression of the Gene is Given across Tumor vs Normal Tissues, Individual Stages of Cancer, based on Patient Weight, and based on the Nodal Metastatic Status of Cancer. A: PRKAA1, B: PRKAA2, C: PRKAB1

Figure 5

The Figure Shows CPTAC Samples Used to Compare the Protein-Level Expression of AMPK Subunits in Normal and Tumor Tissues. A: PRKAA1, B: PRKAA2, C: PRKAB1:D, PRKAB2, E: PRKAG1

Figure 6

The Figure Represents the Promoter Methylation Level of the Subunits of AMPK. The data used to compare the samples are collected from TCGA. A: PRKAA1, B: PRKAA2, C: PRKAB1:D, PRKAB2, E: PRKAG1, F: PRKAG2, G: PRKAG3

Figure 7

The KM Plot of the AMPK Subunits. The figure depicts the OS of the patients in lower and higher expression of the subunits. HR: Hazard Ratio

Figure 8

GO Analysis of AMPK (A) PPI Network analysis (B) by String of the most Mutated 20 Genes in COAD Patients