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

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.

Plunging Ranula Presenting as a Giant Anterior Cervical Cystic Mass: A Case Report and Literature Review.

Plunging ranula, a subtype of ranula, commonly presents as a submandibular or submental cystic mass without oral counterpart, and its clinical management remains challenging. Herein, the authors report an extremely rare case of 30-year-old female patient with plunging ranula involving the root of the left anterior neck.

Tailoring biomaterials and applications targeting tumor-associated macrophages in cancers.

Tumor-associated macrophages (TAMs) play a critical role in supporting tumor growth and metastasis, taming host immunosurveillance, and augmenting therapeutic resistance. As the current treatment paradigms for cancers are generally insufficient to exterminate cancer cells, anti-cancer therapeutic strategies targeting TAMs have been developed. Since TAMs are highly heterogeneous and the pro-tumoral functions are mediated by phenotypes with canonical surface markers, TAM-associated materials exert anti-tumor functions by either inhibiting polarization to the pro-tumoral phenotype or decreasing the abundance of TAMs. Furthermore, TAMs in association with the immunosuppressive tumor microenvironment (TME) and tumor immunity have been extensively exploited in mounting evidence, and could act as carriers or accessory cells of anti-tumor biomaterials. Recently, a variety of TAM-based materials with the capacity to target and eliminate cancer cells have been increasingly developed for basic research and clinical practice. As various TAM-based biomaterials, including antibodies, nanoparticles, RNAs, etc., have been shown to have potential anti-tumor effects reversing the TME, in this review, we systematically summarize the current studies to fully interpret the specific properties and various effects of TAM-related biomaterials, highlighting the potential clinical applications of targeting the crosstalk among TAMs, tumor cells, and immune cells in anti-cancer therapy.

Identifying tumor antigens and immuno-subtyping in colon adenocarcinoma to facilitate the development of mRNA vaccine.

The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1-IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune-hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)-related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA-based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.

Identifying the hub genes in non-small cell lung cancer by integrated bioinformatics methods and analyzing the prognostic values.

BACKGROUND: Lung cancer, a malignant tumor, has the highest mortality and second most common morbidity worldwide. Non-small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer. This study aimed to identify the gene signature associated with the NSCLC prognosis using bioinformatics analysis. MATERIALS AND METHODS: The dataset GSE103512 was utilized to construct co-expression networks using weighted gene co-expression network analysis (WGCNA). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using Database for Annotation, Visualization, and Integrated Discovery. Gene set enrichment analysis was conducted to ascertain the function of the hub genes more accurately. The relationship between the hub genes and immune infiltration was investigated using a single sample gene set enrichment analysis. Hub genes were screened and validated by other datasets and online websites. RESULTS: The results of WGCNA demonstrated that the blue module was most significantly related to tumor progression in NSCLC. Functional enrichment analysis showed that the blue module was associated with DNA replication, cell division, mitotic nuclear division, and cell cycle. A total of five hub genes (RFC5, UBE2S, CHAF1A, FANCI, and TMEM194A) were chosen to be identified and validated at transcriptional and translational levels. Receiver operating characteristic curve verified that the mRNA levels of these five genes can excellently discriminate between normal and tumor tissues. Survival analysis was also performed. Additionally, the protein levels of these five genes were also significantly different between tumor and normal tissues. Immune infiltration analysis showed that the expression levels of the hub genes had a negative correlation with the infiltration levels of many cells related to innate immune response, antigen-presenting process, humoral immune response, or T cell-mediated immune responses. CONCLUSIONS: We identified five hub genes associated with the NSCLC tumorigenesis. NSCLC patients with higher expressions of each hub gene had a worse prognosis than those with lower expressions. Moreover, the hub genes might serve as biomarkers and therapeutic targets for precise diagnosis, target therapy, and immunotherapy of NSCLC in the future.

Potential Immune Biomarker Candidates and Immune Subtypes of Lung Adenocarcinoma for Developing mRNA Vaccines.

mRNA vaccines against cancer have advantages in safety, improved therapeutic efficacy, and large-scale production. Therefore, our purpose is to identify immune biomarkers and to analyze immune status for developing mRNA vaccines and selecting appropriate patients for vaccination. We downloaded clinical information and RNA-seq data of 494 LUAD patients from TCGA. LUAD mutational information was hierarchically clustered by NMF package (Version 0.23.0). DeconstructSigs package (Version 1.8.0) and NMF consistency clustering were used to identify mutation signatures. Maftools package (Version 2.6.05) was used to select LUAD-related immune biomarkers. TIMER was used to discuss the correlation between genetic mutations and cellular components. Unsupervised clustering Pam method was used to identify LUAD immune subtypes. Log-rank test and univariate/multivariate cox regression were used to predict the prognosis of immune subtypes. Dimensionality reduction analysis was dedicated to the description of LUAD immune landscape. LUAD patients are classified into four signatures: T >C, APOBEC mutation, age, and tobacco. Then, GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Next, we clustered five LUAD-related immune subtypes (IS1-IS5) by prognostic prediction. IS3 showed prolonged survival. The reliability of our five immune subtypes was validated by Thorsson's results. IS2 and IS4 patients had high tumor mutation burden and large number of somatic mutations. Besides, we identified that immune subtypes of cold immunity (patients with IS2 and IS4) are ideal mRNA vaccination recipients. Finally, LUAD immune landscape revealed immune cells and prognostic conditions, which provides important information to select patients for vaccination. GPRIN1, MYRF, PLXNB2, SLC9A4, TRIM29, UBA6, and XDH are potential LUAD-related immune biomarker candidates to activate the immune response. Patients with IS2 and IS4 might potentially be immunization-sensitive patients for vaccination.