The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins

Abstract

Background There is no unified treatment standard for patients with extranodal NK/T-cell lymphoma (ENKTL). Cancer neoantigens are the result of somatic mutations and cancer-specific. Increased number of somatic mutations are associated with anti-cancer effects. Screening out ENKTL-specific neoantigens on the surface of cancer cells relies on the understanding of ENKTL mutation patterns. Hence, it is imperative to identify ENKTL-specific genes for ENKTL diagnosis, the discovery of tumor-specific neoantigens and the development of novel therapeutic strategies. We investigated the gene signatures of ENKTL patients. Methods We collected the peripheral blood of a pair of twins for sequencing to identify unique variant genes. One of the twins is diagnosed with ENKTL. Seventy samples were analyzed by Robust Multi-array Analysis (RMA). Two methods (elastic net and Support Vector Machine-Recursive Feature Elimination) were used to select unique genes. Next, we performed functional enrichment analysis and pathway enrichment analysis. Then, we conducted single-sample gene set enrichment analysis of immune infiltration and validated the expression of the screened markers with limma packages. Results We screened out 126 unique variant genes. Among them, 11 unique genes were selected by the combination of elastic net and Support Vector Machine-Recursive Feature Elimination. Subsequently, GO and KEGG analysis indicated the biological function of identified unique genes. GSEA indicated five immunity-related pathways with high signature scores. In patients with ENKTL and the group with high signature scores, a proportion of functional immune cells are all of great infiltration. We finally found that CDC27, ZNF141, FCGR2C and NES were four significantly differential genes in ENKTL patients. ZNF141, FCGR2C and NES were upregulated in patients with ENKTL, while CDC27 was significantly downregulated. Conclusion We identified four ENKTL markers (ZNF141, FCGR2C, NES and CDC27) in patients with extranodal NK/T-cell lymphoma.

FCGR2C: An emerging immune gene for predicting sepsis outcome

“…Moreover, FCGR2C is related to genetic variation in immune and alloimmune diseases (30). Consistent with our study, Wang Y et al found that FCGR2C was a significantly differential gene in extranodal NK/T-cell lymphoma (ENKTL) patients from West China Hospital in Sichuan, China (37). Nevertheless, Breunis WB et al first reported that in 91% of the white control population, a single nucleotide polymorphism(SNP) mutation of exon 3 (rs759550223) resulted in the lack of functional expression of the FCGR2C in their immune cells (30,38).…”

“…Furthermore, we found that FCGR2C was negatively correlated with T-cell subtypes, such as Tem, Tfh, and Th2 cells, by ImmuCellAI analysis. Also, FCGR2C was associated with robust dendritic cells (DC) and T-cells (37). Therefore, FCGR2C may be related to the functional maintenance of immune cells.…”

Development and validation of novel prognostic models for zinc finger proteins-related genes in soft tissue sarcoma

“…Our results suggest that ZNF141 promotes the proliferation and viability of STS cells. Recent studies suggest that ZNF141 is a potential marker of extranodal NK/T-cell lymphoma [ 29 ]. Therefore, we could conclude that ZNF141 played critical roles in promoting progression of STS and may serve as a potential prognostic biomarker.…”