Abstract
Fumarate hydratase (FH) is an important enzymatic component in the tricarboxylic acid cycle. Studies have reported that FH plays an important role in hereditary leiomyomatosis and renal cell cancer (HLRCC). However, the role of FH in human different cancers remains unknown. This study is aimed at analyzing the prognostic value of FH and demonstrating the correlation between FH expression and tumor immunity. Results showed that FH was mutated or copy number varied in 27 types of cancer. FH mRNA was abnormally upregulated across various cancers. Survival analysis suggested high expression of FH was associated with poor prognosis in many cancer types, including lung adenocarcinoma (LUAD). Additionally, FH expression was associated with immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in liver hepatocellular carcinoma (LIHC), LUAD, and lung squamous cell carcinoma (LUSC). Moreover, FH expression showed a strong correlation with immune checkpoint markers in LUAD and testicular germ cell tumors (TGCT). These results indicate that FH is an immunotherapeutic target and a potential prognostic biomarker in LUAD.
Highlights
Cancer is the leading cause of death worldwide, and most existing therapies are low effective [1,2,3]
Our results provide new insights into the role of Fumarate hydratase (FH) in tumors, suggesting that FH is related to the immune infiltration of a variety of tumors and is a potential prognostic biomarker, especially in lung adenocarcinoma (LUAD)
We explored the relationship between FH expression and tumor mutational burden (TMB) level
Summary
Cancer is the leading cause of death worldwide, and most existing therapies are low effective [1,2,3]. Pan-cancer analysis can be used to find valuable prognostic biomarkers [8,9,10]. Pan-cancer analysis is an important method for identifying new diagnostic biomarkers and developing more effective molecular targets for cancer treatment. A growing number of studies have shown that FH is involved in the occurrence and development of certain cancers. Patients with FH gene mutations have a very high risk of hereditary leiomyomatosis and HLRCC [12]. Gastric cancer patients with high FH expression had a higher risk of death than those with low FH expression [13]. The role of FH in pan-cancers needs further study
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