Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor

Abstract

Thymomas and thymic carcinomas are malignant thymic epithelial tumors (TETs) with poor outcomes if non-resectable. However, the tumorigenesis, especially the metabolic mechanisms involved, is poorly studied. Untargeted metabolomics analysis was utilized to screen for differential metabolic profiles between thymic cancerous tissues and adjunct noncancerous tissues. Combined with transcriptomic data, we comprehensively evaluated the metabolic patterns of TETs. Metabolic scores were constructed to quantify the metabolic patterns of individual tumors. Subsequent investigation of distinct clinical outcomes and the immune landscape associated with the metabolic scores was conducted. Two distinct metabolic patterns and differential metabolic scores were identified between TETs, which were enriched in a variety of biological pathways and correlated with clinical outcomes. In particular, a high metabolic score was highly associated with poorer survival outcomes and immunosuppressive status. More importantly, the expression of two prognostic genes (ASNS and BLVRA) identified from differential metabolism-related genes was significantly associated with patient survival and may play a key role in the tumorigenesis of TETs. Our findings suggest that differential metabolic patterns in TETs are relevant to tumorigenesis and clinical outcome. Specific transcriptomic alterations in differential metabolism-related genes may serve as predictive biomarkers of survival outcomes and potential targets for the treatment of patients with TETs.

Ultrahigh‐performance liquid chromatography–high‐resolution mass spectrometry‐based plasma metabolomics study of thymoma and thymic hyperplasia

“…Many of the metabolites had increased concentration in aggressive thymoma (types B2 and B3) compared to indolent thymoma (A, AB and B1), including histidine, phenylalanine, isoleucine and tyrosine 5 . In a recent metabolomic and transcriptomic study of tissue samples from 32 TET patients, a metabolic score was determined from metabolic signature genes and higher metabolic scores were found to be significantly associated with creatine, phenylalanine and tyrosine metabolism activation and also highly associated with immunosuppressive status and poorer survival outcomes 17 . The results of our study were in accordance with the above findings.…”

“…The results indicated a strong “Warburg effect,” glutaminolysis and redox homeostasis as potential vulnerabilities of aggressive TETs, and they might be used as targets for TET treatment, once validated with a larger sample cohort 5 . Tang et al performed UHPLC/MS‐based metabolomic profiling and transcriptomic profiling of tumor tissues and adjacent noncancerous tissues from 32 patients with TETs and identified that glycerophospholipid metabolism, arginine biosynthesis and porphyrin and chlorophyll metabolism might be associated with TET development 17 . Tissue metabolomics is useful for investigating abnormality of metabolism associated with tumor microenvironment and communications between cancer cells 18 .…”

“…5 Tang et al performed UHPLC/MS-based metabolomic profiling and transcriptomic profiling of tumor tissues and adjacent noncancerous tissues from 32 patients with TETs and identified that glycerophospholipid metabolism, arginine biosynthesis and porphyrin and chlorophyll metabolism might be associated with TET development. 17 Tissue metabolomics is useful for investigating abnormality of metabolism associated with tumor microenvironment and communications between cancer cells. 18 Biofluids such as plasma and serum are easily obtained and commonly used samples for studying potential biomarkers in disease detection.…”

Prognostic factors and genetic markers in thymic epithelial tumors: A narrative review

“…52 Tang et al investigated the involvement of two metabolism-related genes (MRGs), ASNS and BLVRA in TET. 54 Both genes were strongly associated with survival in these patients. Hou et al revealed that thymic carcinomas had significantly lower expression of HMGB1, a proinflammatory cytokine-related gene, compared to thymomas.…”

“…Tang et al investigated the involvement of two metabolism‐related genes (MRGs), ASNS and BLVRA in TET 54 . Both genes were strongly associated with survival in these patients.…”