The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma
Objective Gene mutations in tumor cells can lead to several unique metabolic phenotypes, which are crucial for the proliferation of cancer cells. EGFR mutation (EGFR-mt) is the main oncogenic driving mutation in lung adenocarcinoma (LUAD). HIF-1 α and PKM2 are two key metabolic regulatory proteins t...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-01-01
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| Series: | Journal of Investigative Surgery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/08941939.2023.2301081 |
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| author | Yuan Wang Hongguang Lian Jiajun Li Man Zhao Zengfang Hao Xue Zheng Linyuan Zhao Jinfeng Cui |
| author_facet | Yuan Wang Hongguang Lian Jiajun Li Man Zhao Zengfang Hao Xue Zheng Linyuan Zhao Jinfeng Cui |
| author_sort | Yuan Wang |
| collection | DOAJ |
| description | Objective Gene mutations in tumor cells can lead to several unique metabolic phenotypes, which are crucial for the proliferation of cancer cells. EGFR mutation (EGFR-mt) is the main oncogenic driving mutation in lung adenocarcinoma (LUAD). HIF-1 α and PKM2 are two key metabolic regulatory proteins that can form a feedback loop and promote cancer growth by promoting glycolysis. Here, the linkage between EGFR mutational status and HIF-1α/PKM2 feedback loop in LUAD were evaluated.Methods Retrospective study were performed on LUAD patients (n = 89) undergoing first-time therapeutic surgical resection. EGFR mutation was analyzed by real-time PCR. Immunohistochemistry was used to measure the expressions of HIF-1α and PKM2.Results We found that the protein expressions of HIF-1α and PKM2 were significantly higher in LUAD than normal lung tissues. In adenocarcinomas, the two protein expressions were both correlated with worse pTNM stage. Moreover, the correlation between the proteins of HIF-1α/PKM2 feedback loop and the EGFR mutational status were also analyzed. We found that EGFR-mt tumors showed higher HIF-1α and PKM2 proteins compared to tumors with EGFR wild-type. Meanwhile, HIF-1α expression was significantly correlated with higher pTNM stage, and PKM2 showed a similar trend, only in EGFR-mutated tumors. The expression of HIF-1α was positively correlated with PKM2 in LUAD, furthermore, this correlation was mainly in patients with EGFR-mt.Conclusion Different expression and clinical features of HIF-1α/PKM2 feedback loop was existed between LUAD and normal lung tissues, especially in EGFR mutational tumors, supporting the relationship between EGFR mutation and the key related proteins of aerobic glycolysis (HIF-1α and PKM2) in lung adenocarcinomas. |
| format | Article |
| id | doaj-art-2ca42b79b696480598626ebcb76c8457 |
| institution | OA Journals |
| issn | 0894-1939 1521-0553 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Investigative Surgery |
| spelling | doaj-art-2ca42b79b696480598626ebcb76c84572025-08-20T02:32:27ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532024-01-0137110.1080/08941939.2023.2301081The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung AdenocarcinomaYuan Wang0Hongguang Lian1Jiajun Li2Man Zhao3Zengfang Hao4Xue Zheng5Linyuan Zhao6Jinfeng Cui7Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaLaboratory of Pathology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaDepartment of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, ChinaObjective Gene mutations in tumor cells can lead to several unique metabolic phenotypes, which are crucial for the proliferation of cancer cells. EGFR mutation (EGFR-mt) is the main oncogenic driving mutation in lung adenocarcinoma (LUAD). HIF-1 α and PKM2 are two key metabolic regulatory proteins that can form a feedback loop and promote cancer growth by promoting glycolysis. Here, the linkage between EGFR mutational status and HIF-1α/PKM2 feedback loop in LUAD were evaluated.Methods Retrospective study were performed on LUAD patients (n = 89) undergoing first-time therapeutic surgical resection. EGFR mutation was analyzed by real-time PCR. Immunohistochemistry was used to measure the expressions of HIF-1α and PKM2.Results We found that the protein expressions of HIF-1α and PKM2 were significantly higher in LUAD than normal lung tissues. In adenocarcinomas, the two protein expressions were both correlated with worse pTNM stage. Moreover, the correlation between the proteins of HIF-1α/PKM2 feedback loop and the EGFR mutational status were also analyzed. We found that EGFR-mt tumors showed higher HIF-1α and PKM2 proteins compared to tumors with EGFR wild-type. Meanwhile, HIF-1α expression was significantly correlated with higher pTNM stage, and PKM2 showed a similar trend, only in EGFR-mutated tumors. The expression of HIF-1α was positively correlated with PKM2 in LUAD, furthermore, this correlation was mainly in patients with EGFR-mt.Conclusion Different expression and clinical features of HIF-1α/PKM2 feedback loop was existed between LUAD and normal lung tissues, especially in EGFR mutational tumors, supporting the relationship between EGFR mutation and the key related proteins of aerobic glycolysis (HIF-1α and PKM2) in lung adenocarcinomas.https://www.tandfonline.com/doi/10.1080/08941939.2023.2301081lung adenocarcinomaglycolysisHIF-1αPKM2EGFR |
| spellingShingle | Yuan Wang Hongguang Lian Jiajun Li Man Zhao Zengfang Hao Xue Zheng Linyuan Zhao Jinfeng Cui The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma Journal of Investigative Surgery lung adenocarcinoma glycolysis HIF-1α PKM2 EGFR |
| title | The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma |
| title_full | The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma |
| title_fullStr | The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma |
| title_full_unstemmed | The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma |
| title_short | The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma |
| title_sort | hif 1α pkm2 feedback loop in relation to egfr mutational status in lung adenocarcinoma |
| topic | lung adenocarcinoma glycolysis HIF-1α PKM2 EGFR |
| url | https://www.tandfonline.com/doi/10.1080/08941939.2023.2301081 |
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