Immune Infiltration
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2021 ◽  
Vol 12 ◽  
Yi-Yuan Qu ◽  
Rong-Yan Guo ◽  
Meng-Ling Luo ◽  
Quan Zhou

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.

2021 ◽  
Vol 8 ◽  
Xing Liu ◽  
Shiyue Xu ◽  
Ying Li ◽  
Qian Chen ◽  
Yuanyuan Zhang ◽  

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.

2021 ◽  
Vol Volume 8 ◽  
pp. 1495-1511
Xin Liu ◽  
Yize Zhang ◽  
Zenghan Wang ◽  
Liwen Liu ◽  
Guizhen Zhang ◽  

Bioengineered ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 10905-10923
Jianfeng Ding ◽  
Xiaobo He ◽  
Jinkun Wang ◽  
Guodong Cao ◽  
Sihan Chen ◽  

2021 ◽  
Vol 5 (6) ◽  
pp. 1-15
Ting Li ◽  
Jiankai Feng ◽  
Pihong Yan ◽  
Hongwei Tan ◽  
Lili Wang ◽  

This study was conducted to explore the correlations between the expression, methylation, and various clinicopathological factors of purinergic P2X1 receptor (P2RX1) and the prognosis of patients with gastrointestinal tumors. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were used to analyze the expression of P2RX1 in different types of gastrointestinal cancers. Kaplan-Meier analysis and univariate Cox regression analysis were used to analyze the correlations between P2RX1 expression and the prognosis of various gastrointestinal tumors. Correlations between P2RX1 expression and N6 methyladenine (m6A)-related genes as well as immune checkpoint genes were analyzed by R packages (R version: 4.0.3) based on TCGA database. The association between P2RX1 methylation level and the prognosis of patients with gastrointestinal cancers was analyzed using the MethSurv database. In order to explore the biological functions of P2RX1 in hepatocellular carcinoma, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were carried out using R software. In order to evaluate the correlations between P2RX1 and tumor immune infiltration, Spearman correlation test was performed. The correlations between P2RX1 expression and immune score as well as immune checkpoint genes were analyzed based on TCGA and Tumor Immune Estimation Resource (TIMER) databases. The expression of P2RX1 was found to be significantly downregulated in gastrointestinal tumors except in cholangiocarcinoma (P < 0.05). High expression of P2RX1 tended to present better prognosis in hepatocellular carcinoma (P < 0.05). It was noted that cg06475633 of P2RX1 presented a higher methylation level compared with other CpG sites in hepatocellular carcinoma. Overall, six CpGs of P2RX1 were associated with significant prognosis in patients with hepatocellular carcinoma (P < 0.05). Among all the 20 m6A-related genes, Wilms’ tumor 1-associating protein (WTAP) was the most strongly correlated with P2RX1 in hepatocellular carcinoma. Gene enrichment analysis showed that P2RX1 is widely involved in the proliferation, activation, organization, and differentiation of various immune cells. After investigating the TIMER database, P2RX1 was found to be tightly correlated with immune infiltrating cells in gastrointestinal tumors, especially with dendritic cells. Moreover, P2RX1 was found to be strongly positively associated with programmed cell death 1 (PD1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in hepatocellular carcinoma (P < 0.05). In conclusion, the dual role of P2RX1 in cancers and its involvement in the recruitment as well as regulation of tumor infiltrating cells in gastrointestinal cancers may be appreciated through this study.

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6002
Baoyi Zhang ◽  
Kevin Yao ◽  
Min Xu ◽  
Jia Wu ◽  
Chao Cheng

EBV infection occurs in around 10% of gastric cancer cases and represents a distinct subtype, characterized by a unique mutation profile, hypermethylation, and overexpression of PD-L1. Moreover, EBV positive gastric cancer tends to have higher immune infiltration and a better prognosis. EBV infection status in gastric cancer is most commonly determined using PCR and in situ hybridization, but such a method requires good nucleic acid preservation. Detection of EBV status with histopathology images may complement PCR and in situ hybridization as a first step of EBV infection assessment. Here, we developed a deep learning-based algorithm to directly predict EBV infection in gastric cancer from H&E stained histopathology slides. Our model can not only predict EBV infection in gastric cancers from tumor regions but also from normal regions with potential changes induced by adjacent EBV+ regions within each H&E slide. Furthermore, in cohorts with zero EBV abundances, a significant difference of immune infiltration between high and low EBV score samples was observed, consistent with the immune infiltration difference observed between EBV positive and negative samples. Therefore, we hypothesized that our model’s prediction of EBV infection is partially driven by the spatial information of immune cell composition, which was supported by mostly positive local correlations between the EBV score and immune infiltration in both tumor and normal regions across all H&E slides. Finally, EBV scores calculated from our model were found to be significantly associated with prognosis. This framework can be readily applied to develop interpretable models for prediction of virus infection across cancers.

Aging ◽  
2021 ◽  
Do Thi Minh Xuan ◽  
Chung-Che Wu ◽  
Tzu-Jen Kao ◽  
Hoang Dang Khoa Ta ◽  
Gangga Anuraga ◽  

2021 ◽  
Vol 19 (1) ◽  
Ilana Schlam ◽  
Sarah E. Church ◽  
Tyler D. Hether ◽  
Krysta Chaldekas ◽  
Briana M. Hudson ◽  

Abstract Background The characterization of the immune component of the tumor microenvironment (TME) of human epidermal growth factor receptor 2 positive (HER2+) breast cancer has been limited. Molecular and spatial characterization of HER2+ TME of primary, recurrent, and metastatic breast tumors has the potential to identify immune mediated mechanisms and biomarker targets that could be used to guide selection of therapies. Methods We examined 15 specimens from eight patients with HER2+ breast cancer: 10 primary breast tumors (PBT), two soft tissue, one lung, and two brain metastases (BM). Using molecular profiling by bulk gene expression TME signatures, including the Tumor Inflammation Signature (TIS) and PAM50 subtyping, as well as spatial characterization of immune hot, warm, and cold regions in the stroma and tumor epithelium using 64 protein targets on the GeoMx Digital Spatial Profiler. Results PBT had higher infiltration of immune cells relative to metastatic sites and higher protein and gene expression of immune activation markers when compared to metastatic sites. TIS scores were lower in metastases, particularly in BM. BM also had less immune infiltration overall, but in the stromal compartment with the highest density of immune infiltration had similar levels of T cells that were less activated than PBT stromal regions suggesting immune exclusion in the tumor epithelium. Conclusions Our findings show stromal and tumor localized immune cells in the TME are more active in primary versus metastatic disease. This suggests patients with early HER2+ breast cancer could have more benefit from immune-targeting therapies than patients with advanced disease.

2021 ◽  
Vol 12 ◽  
Yangfan Zhou ◽  
Yuan Fang ◽  
Junjie Zhou ◽  
Yulian Liu ◽  
Shusheng Wu ◽  

Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunotherapy in ES are yet to be developed. In our study, we first identified the immune-associated differential hub gene NPM1 by bioinformatics methods as a differentially expressed gene, and then validated it using real time-PCR and western blotting, and found that this gene is not only closely related to the immune infiltration in ES, but also can affect the proliferation and apoptosis of ES cells, and is closely related to the survival of patients. The results of our bioinformatic analysis showed that NPM1 can be a hub gene in ES and an immunotherapeutic target to reactivate immune infiltration in patients with ES. In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES.

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