Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer

Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-p...

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Main Authors: Junping Zhang, Xiaoping Cai, Weifeng Cui, Zheng Wei
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/10/1786
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author Junping Zhang
Xiaoping Cai
Weifeng Cui
Zheng Wei
author_facet Junping Zhang
Xiaoping Cai
Weifeng Cui
Zheng Wei
author_sort Junping Zhang
collection DOAJ
description Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, <i>p</i>-value 3.111 × 10<sup>−9</sup>), miR-33b-5p (R= −0.238, <i>p</i>-value 1.166 × 10<sup>−5</sup>), and miR-582-3p (R = −0.214, <i>p</i>-value 8.430 × 10<sup>−5</sup>), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.
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spelling doaj.art-4eb32aba7ec8427d95031c26295348312023-12-03T14:45:16ZengMDPI AGGenes2073-44252022-10-011310178610.3390/genes13101786Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric CancerJunping Zhang0Xiaoping Cai1Weifeng Cui2Zheng Wei3Cancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, ChinaCancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, ChinaCancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, ChinaCancer Research Institute, Henan Academy Institute of Chinese Medicine, Zhengzhou 450000, ChinaBackground: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, <i>p</i>-value 3.111 × 10<sup>−9</sup>), miR-33b-5p (R= −0.238, <i>p</i>-value 1.166 × 10<sup>−5</sup>), and miR-582-3p (R = −0.214, <i>p</i>-value 8.430 × 10<sup>−5</sup>), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.https://www.mdpi.com/2073-4425/13/10/1786gastric cancerMAP4K4GSEAmiRNA targetmethylation
spellingShingle Junping Zhang
Xiaoping Cai
Weifeng Cui
Zheng Wei
Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
Genes
gastric cancer
MAP4K4
GSEA
miRNA target
methylation
title Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
title_full Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
title_fullStr Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
title_full_unstemmed Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
title_short Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
title_sort bioinformatics and experimental analyses reveal map4k4 as a potential marker for gastric cancer
topic gastric cancer
MAP4K4
GSEA
miRNA target
methylation
url https://www.mdpi.com/2073-4425/13/10/1786
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