Dataset Information

The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Metabolic dysregulation has emerged as a crucial determinant of the clinical responses to immunotherapy. The aim of this study was to determine the clinical significance of the candidate immune-related metabolic enzymes (IRMEs) methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 (MTHFD2) in head and neck squamous cell carcinoma (HNSCC). The gene expression profile of HNSCC cohort and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed IRMEs were identified, and then, the prognosis-associated IRMEs were revealed by univariate cox regression analysis. The prognostic significance of MTHFD2 in HNSCC as well as the association between MTHFD2 and immune cell infiltration were further analyzed. A total of 121 significantly altered IRMEs were identified between HNSCC and normal tissues, and 21 IRMEs were found to be strongly associated with overall survival of HNSCC. Upregulation of MTHFD2 was positively correlated with adverse clinicopathological factors in TCGA HNSCC cohort, which was further validated with our own cohort using immunohistochemical analysis. Interestingly, bioinformatic analysis further revealed that increased MTHFD2 expression was negatively associated with NK cells activation, while positively correlated with mast cells activation. In conclusion, MTHFD2 overexpression is closely correlated with unfavorable prognosis of HNSCC, and it might play an important role in modulating the tumor immune microenvironment.

SUBMITTER: Cui L

PROVIDER: S-EPMC7555784 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.

Cui Li L Chen Huan H Zhao Xinyuan X

Diagnostics (Basel, Switzerland) 20200911 9

Metabolic dysregulation has emerged as a crucial determinant of the clinical responses to immunotherapy. The aim of this study was to determine the clinical significance of the candidate immune-related metabolic enzymes (IRMEs) methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 (MTHFD2) in head and neck squamous cell carcinoma (HNSCC). The gene expression profile of HNSCC cohort and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). The different ...[more]

PMID: 32933024

Similar Datasets

Project description:The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients. High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers. Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes (PVR, TNFRSF12A, IL21R, and SOCS1) were significantly associated with overall survival (OS). Integrating these genes with Path_N stage, a multiplex model was built and suggested better performance in determining 5 years OS (receiver operating characteristic (ROC) analysis, area under the curve (AUC)=0.709) than others. Further protein-based validation was conducted in 115 HNSCC patients. Similarly, high expression of PVR and TNFRSF12A were associated with poor OS (Kaplan-Meier p=0.017 and 0.0032), while high expression of IL21R and SOCS1 indicated favorable OS (Kaplan-Meier p<0.0001 and =0.0018). The integrated model with Path_N stage still demonstrated efficacy in OS evaluation (Kaplan-Meier p<0.0001, ROC AUC=0.893). Besides, the four prognostic genes were significantly correlated with activated CD8+ T cells, CD4+ T cells, follicular helper T cells and regulatory T cells, implying the possible involvement of these genes in the immunoregulation and development of HNSCC. The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.

Dataset Information

The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.

Publications

The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets