scholarly journals Comprehensive Characterization And Clinical Relevance of CLEC4G Expression Across Human Cancers

Author(s):  
Yong Li ◽  
Huiqin Huang ◽  
Xiangli Ye ◽  
Xiaoping Li ◽  
Zhenghui Huang ◽  
...  

Abstract Liver and lymph node sinusoidal endothelial cell C-type lectin (CLEC4G) interacts with the surface glycoproteins of enveloped viruses and mediates immune evasion for viruses. Recent studies have indicated that the expression of CLEC4G affects the development and microenvironment of tumors. In the present study, we revealed comprehensive characterization of CLEC4G expression across human cancers. We first explored the effect of CLEC4G expression on overall survival (OS) across human cancers. High expression of CLEC4G was beneficial in lung adenocarcinoma (LUAD) and detrimental in kidney renal clear cell carcinoma (KIRC) and uveal melanoma (UVM) in terms of OS. Enrichment analysis of the 14 cancer-related signatures suggested that CLEC4G regulated tumor metastasis and immune response. Enrichment analysis of the immunophenotypes and cancer-immunity cycles indicated that CLEC4G was involved in regulation of macrophages and Treg cells, which affected tumor immune response. We also observed correlations between CLEC4G expression and checkpoint molecular expression in different cancer types. Taken together, the present study revealed the comprehensive characterization of CLEC4G expression across human cancers, predicting the roles of CLEC4G in the development and immune microenvironment of tumors.

2022 ◽  
Vol 12 ◽  
Author(s):  
Meihong Gao ◽  
Shuhui Liu ◽  
Yang Qi ◽  
Xinpeng Guo ◽  
Xuequn Shang

Long non-coding RNAs (lncRNAs) play critical roles in cancer through gene expression and immune regulation. Identifying immune-related lncRNA (irlncRNA) characteristics would contribute to dissecting the mechanism of cancer pathogenesis. Some computational methods have been proposed to identify irlncRNA characteristics in human cancers, but most of them are aimed at identifying irlncRNA characteristics in specific cancer. Here, we proposed a new method, ImReLnc, to recognize irlncRNA characteristics for 33 human cancers and predict the pathogenicity levels of these irlncRNAs across cancer types. We first calculated the heuristic correlation coefficient between lncRNAs and mRNAs for immune-related enrichment analysis. Especially, we analyzed the relationship between lncRNAs and 17 immune-related pathways in 33 cancers to recognize the irlncRNA characteristics of each cancer. Then, we calculated the Pscore of the irlncRNA characteristics to evaluate their pathogenicity levels. The results showed that highly pathogenic irlncRNAs appeared in a higher proportion of known disease databases and had a significant prognostic effect on cancer. In addition, it was found that the expression of irlncRNAs in immune cells was higher than that of non-irlncRNAs, and the proportion of irlncRNAs related to the levels of immune infiltration was much higher than that of non-irlncRNAs. Overall, ImReLnc accurately identified the irlncRNA characteristics in multiple cancers based on the heuristic correlation coefficient. More importantly, ImReLnc effectively evaluated the pathogenicity levels of irlncRNAs across cancer types. ImReLnc is freely available at https://github.com/meihonggao/ImReLnc.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Myung-Chul Kim ◽  
Nicholas Borcherding ◽  
Kawther K. Ahmed ◽  
Andrew P. Voigt ◽  
Ajaykumar Vishwakarma ◽  
...  

AbstractRegulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177+ TI Treg population that may serve as a target for TI Treg-specific immunotherapy.


2020 ◽  
Author(s):  
Ning Zhao ◽  
Liang Wu ◽  
Zili Zhou ◽  
Xudan Zhang ◽  
Shengbo Han ◽  
...  

Abstract Background: Previous studies revealed that cancer-associated differentially expressed genes (DEGs) in an independent cancer type are rarely related to the tumorigenesis and metastasis, while the common DEGs across multiple types of cancer may be proved as potential oncogenes or tumor suppressors. Although tumor-infiltrating immune cells have been reported to be associated with prognosis in multiple types of cancer, the hub genes regulating immune cells function in different cancer types remain unclear. Methods: To screen for the hub genes regulating immune infiltrating level across multiple tumors microenvironment, the raw data containing RNA sequencing and clinical information from TCGA database and immune scores from ESTIMATE website across 25 cancer types were obtained. Results: Based on the immune scores, all cases were categorized into high-score and low-score groups. Kaplan–Meier survival analysis demonstrated that a strong correlation between immune infiltrating level and survival prognosis was found in six cancer types. The functional enrichment analysis of common DEGs revealed that infection and immune response are the most prominent biological characteristics. Subsequently, the twelve common DEGs with prognostic value were identified as candidate hub genes and were adopted to construct the PPI network. Because of highly interconnected with other hub genes, protein tyrosine phosphatase non-receptor type 6 (PTPN6) was selected as the real hub gene across the six immune-specific tumors. Finally, a significant correlation between PTPN6 and immune infiltrating level, and immune marker sets of various immune cells were observed. Conclusion: PTPN6 may play a vital role in regulating immune response for tumor development, due to its significant correlation with tumor-infiltrating immune cells in multiple cancers.


2021 ◽  
Author(s):  
Erik N Bergstrom ◽  
Jens-Christian Luebeck ◽  
Mia Petljak ◽  
Vineet Bafna ◽  
Paul S. Mischel ◽  
...  

Clustered somatic mutations are common in cancer genomes with prior analyses revealing several types of clustered single-base substitutions, including doublet- and multi-base substitutions, diffuse hypermutation termed omikli, and longer strand-coordinated events termed kataegis. Here, we provide a comprehensive characterization of clustered substitutions and clustered small insertions and deletions (indels) across 2,583 whole-genome sequenced cancers from 30 cancer types. While only 3.7% of substitutions and 0.9% of indels were found to be clustered, they contributed 8.4% and 6.9% of substitution and indel drivers, respectively. Multiple distinct mutational processes gave rise to clustered indels including signatures enriched in tobacco smokers and homologous-recombination deficient cancers. Doublet-base substitutions were caused by at least 12 mutational processes, while the majority of multi-base substitutions were generated by either tobacco smoking or exposure to ultraviolet light. Omikli events, previously attributed to the activity of APOBEC3 deaminases, accounted for a large proportion of clustered substitutions. However, only 16.2% of omikli matched APOBEC3 patterns with experimental validation confirming additional mutational processes giving rise to omikli. Kataegis was generated by multiple mutational processes with 76.1% of all kataegic events exhibiting AID/APOBEC3-associated mutational patterns. Co-occurrence of APOBEC3 kataegis and extrachromosomal-DNA (ecDNA) was observed in 31% of samples with ecDNA. Multiple distinct APOBEC3 kataegic events were observed on most mutated ecDNA. ecDNA containing known cancer genes exhibited both positive selection and kataegic hypermutation. Our results reveal the diversity of clustered mutational processes in human cancer and the role of APOBEC3 in recurrently mutating and fueling the evolution of ecDNA.


2018 ◽  
Author(s):  
Youqiong Ye ◽  
Yu Xiang ◽  
Joseph Takahashi ◽  
Gordon Mills ◽  
Seung-Hee Yoo ◽  
...  

2020 ◽  
Author(s):  
Ning Zhao ◽  
Liang Wu ◽  
Zili Zhou ◽  
Xudan Zhang ◽  
Shengbo Han ◽  
...  

Abstract Background Previous studies revealed that cancer-associated differentially expressed genes (DEGs) in an independent cancer type are rarely related to the tumorigenesis and metastasis, while the common DEGs across multiple types of cancer may be proved as potential oncogenes or tumor suppressors and extend our understanding. Although tumor-infiltrating lymphocytes (TIL) have been reported to be associated with prognosis in multiple types of cancer, the hub genes regulating immune cells function in different cancer types remain unclear.Methods To screen for the hub genes regulating immune infiltrating level across multiple tumors microenvironment, the raw data containing RNA sequencing and clinical information from TCGA database and immune scores from ESTIMATE website across 25 cancer types were obtained.Results Based on the immune scores, all cases were categorized into high-score and low-score groups. Kaplan–Meier survival analysis demonstrated that a strong correlation was found in six cancer types. The functional enrichment analysis of common DEGs revealed that infection and immune response are the most prominent biological characteristics. Subsequently, the twelve common DEGs with prognostic value were identified as candidate hub genes and were adopted to construct the PPI network. Because of highly interconnected with other hub genes, protein tyrosine phosphatase non-receptor type 6 (PTPN6) was selected as the real hub gene across the six immune-specific tumors.Conclusion Due to the significant correlation between PTPN6 with tumor-infiltrating immune cells in multiple cancers, PTPN6 may well play a vital role in regulating immune response for tumor development.


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