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2021 ◽  
Author(s):  
Yuanbin Zhong

Abstract Background Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Many recent studies have suggested that pyroptosis is important in tumour progression. However, the role of pyroptosis-related genes (PRGs) in HCC remains unclear. Materials and methods We identified differentially expressed PRGs in tumours versus normal tissues. Through univariate, LASSO, and multivariate Cox regression analyses, a prognostic PRG signature was established. The signature effectiveness was evaluated by time-dependent receiver operating characteristic (ROC) curve and Kaplan–Meier (KM) survival analysis. The signature was validated in the ICGC (LIRI-JP) cohort. In addition, single-sample gene enrichment analysis (ssGSEA) showed the infiltration of major immune cell types and the activity of common immune pathways in different subgroups. Results Twenty-nine pyroptosis-related DEGs from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were detected, and four genes (CTSV, CXCL8, MKI67 and PRF1) among them were selected to construct a prognostic signature. Then, the patients were divided into high- and low-risk groups. The pyroptosis-related signature was significantly associated with overall survival (OS). In addition, the patients in the high-risk group had lower levels of immune infiltration. Conclusion The prognostic signature for HCC based on 4 pyroptosis-related genes has reliable prognostic and predictive value for HCC patients.


2021 ◽  
pp. 1-17
Author(s):  
Zhihao Huang ◽  
Aoxiao He ◽  
Jiakun Wang ◽  
Hongcheng Lu ◽  
Xiaoyun Xu ◽  
...  

BACKGROUND: Toll-like receptors participate in various biological mechanisms, mainly including the immune response and inflammatory response. Nevertheless, the role of TLRs in STAD remains unclear. OBJECTIVE: We aimed to explore the expression, prognosis performance of TLRs in STAD and their relationship with immune infiltration. METHODS: Student’s t-test was used to evaluate the expression of TLRs between STAD tissues and normal tissues. Kaplan-Meier method was applied to explored the prognosis value of TLRs in STAD. And qRT-PCR validated their expression and prognosis value. Spearman’s correlation analysis and Wilcoxon rank-sum test were used to assess the association between TLRs and immune infiltration in STAD. RESULTS: The mRNA level of TLR3 was downregulated in STAD. We summarized genetic mutations and CNV alteration of TLRs in STAD cohort. Prognosis analysis revealed that STAD patients with high TLR3 expression showed better prognosis in OS, FP and PPS. The result of qRT-PCR suggested that TLR3 expression was decreased in STAD tissues and STAD patients with high TLR3 mRNA level had a better OS. Univariate and multivariate cox regression analysis suggested TLR3 expression and clinical stage as independent factors affecting STAD patients’ prognosis. A positive association existed between TLR3 expression and the abundance of immune cells and the expression of various immune biomarkers. Furthermore, key targets related to TLR3 were identified in STAD, mainly including MIR-129 (GCAAAAA), PLK1, and V$IRF1_01. CONCLUSIONS: Our result demonstrated TLR3 as a prognosis marker and associated with immune infiltration in STAD.


2021 ◽  
Author(s):  
Yongjie Li ◽  
Min Zeng ◽  
Ting Wang ◽  
Feng Jiang

Abstract Pancreatic cancer is a malignant tumor of digestive system with high fatality rate, and its prognosis is very poor. Type Ⅴ collagen α3 (COL5A3) is highly expressed in a variety of tumor tissues, but its prognostic value and immune infiltration in pancreatic cancer are still unclear. Therefore, we evaluated the prognostic role of COL5A3 in pancreatic cancer and its correlation with immune infiltration. The transcriptional expression profiles of COL5A3 in pancreatic cancer and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). In the GEO (Gene expression omnibus) dataset (GSE16515), we compared the expression of COL5A3 in normal and tumor tissues. The expression of COL5A3 protein was evaluated by the human protein atlas (THPA). The effect of COL5A3 on survival was evaluated by Kaplan-Meier method. Receiver operating characteristic (ROC) curve was used to distinguish pancreatic cancer from paracancerous normal tissues. Protein-protein interaction (PPI) network was constructed by the STRING. Use the "ClusterProfiler" package for functional enrichment analysis. Tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were used to determine the relationship between COL5A3 mRNA expression and immune infiltration. Compared with normal tissues, COL5A3 is highly expressed in pancreatic cancer tissues. The high expression of COL5A3 is related to the poor clinicopathological features and poor prognosis of pancreatic cancer. Kaplan-Meier survival analysis showed that the prognosis of pancreatic cancer patients with high expression of COL5A3 was worse than that of patients with low expression of COL5A3. ROC curve shows that COL5A3 has high sensitivity and specificity in the diagnosis of pancreatic cancer. Correlation analysis showed that the expression of COL5A3 mRNA was related to immune cell infiltration. This study reveals for the first time that COL5A3 may be a new prognostic biomarker related to immune infiltration and provide a new target for the diagnosis and treatment of pancreatic cancer.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ya-Ming Meng ◽  
Xue Jiang ◽  
Xinbao Zhao ◽  
Qiong Meng ◽  
Sangqing Wu ◽  
...  

AbstractDefective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.


2021 ◽  
Author(s):  
Wensheng Qiu

Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from the TCGA database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS, but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yeon Chae ◽  
Taesik Yun ◽  
Yoonhoi Koo ◽  
Dohee Lee ◽  
Hakhyun Kim ◽  
...  

This study aimed to identify the physiological 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in cats using positron emission tomography/computed tomography (PET/CT) and determine its characteristics by comparing physiological differences with dogs. Seven healthy cats and six healthy beagle dogs were examined using FDG-PET/CT. Regions of interest (ROIs) were manually drawn over 41 detailed structures of 5 gross structures (brain, head and neck, musculoskeleton, thorax, and abdomen). The mean and maximum standard uptake values (SUVmean and SUVmax) were calculated for each ROI. Physiological variation was classified as having increased radiopharmaceutical activity with no evidence of abnormal clinical or radiological findings. The brain had the highest SUV, which was observed in the cerebellum of both cats (SUVmean: 4.90 ± 1.04, SUVmax: 6.04 ± 1.24) and dogs (SUVmean: 3.15 ± 0.57, SUVmax: 3.90 ± 0.74). Cats had a significantly higher intracranial uptake than dogs did (P < 0.01). In the digestive system, the SUVs of the duodenum and jejunum were significantly higher in dogs than in cats (P < 0.05). FDG uptake of the submandibular tip, tonsils, neck of the gallbladder, and caudal colliculus were physiologically increased in cats. This study demonstrates physiological FDG uptake in normal tissues, and the differences between cats and dogs were interpreted based on species-specificity. This information contributes to improving the accurate diagnosis of cancer in cats and will aid in understanding glucose metabolism in both cats and dogs.


2021 ◽  
Author(s):  
Yuanshan Cui ◽  
Zhongbao Zhou ◽  
Yumeng Chai ◽  
Yong Zhang

Abstract Background: Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in Clear Cell Renal Cell Carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. Methods: The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from the Cancer Genome Atlas (TCGA), and additionally verified in a different independent cohort, which was obtained from the gene expression omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were accessed to assess the protein expression of GSDMB. To differentiate between ccRCC and surrounding normal tissues, the receiver operating characteristic (ROC) curve was applied. Relationships between GSDMB expression, clinicopathologicical variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with String. Functional enrichment analyses were conducted by utilizing the “ClusterProfiler” package. The tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. Results: GSDMB expression was significantly more up regulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high-GSDMB had a poorer prognosis compared to those with low-GSDMB (P < 0.001). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. Conclusions: The results of this study indicates that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.


2021 ◽  
Author(s):  
Yisheng Peng ◽  
Jun Fan ◽  
Gang Zhu ◽  
Shunde Tan ◽  
Jianfei Chen ◽  
...  

Abstract Background: According to reports, LIMK1 may have the effect of promoting tumor progression. However, the effect of the expression of LIMK1 on the healing of patients with hepatocellular carcinoma and its effect on the immune function are still not clear. Therefore, we analyzed the effect of LIMK1 on the healing of patients with hepatocellular carcinoma and its correlation with immunity through bioinformatics analysis.Methods: Download the transcriptional expression profile of LIMK1 in hepatocellular carcinoma tissues and normal tissues in TCGA, and study its expression in hepatocellular carcinoma. Study the expression of LIMK1 in hepatocellular carcinoma through CPTAC and HPA database. The Kaplan-Meier method was used to evaluate the effect of LIMK1 expression on the survival of patients with hepatocellular carcinoma. Use the STRING database to construct a protein-protein interaction (PPI) network. Use the "ClusterProfiler" package for feature-rich analysis. Use TISIDB database and Xiantao platform to study the relationship between LIMK1 mRNA expression and immune infiltration.Results: The expression of LIMK1 in hepatocellular carcinoma tissues was significantly up-regulated. Increased expression of LIMK1 mRNA is related to high TNM staging. In the ROC curve, when the cut-off level is 1.813, the sensitivity and specificity of LIMK1 to distinguish hepatocellular carcinoma from adjacent controls are 80.7% and 86%, respectively.The Kaplan-Meier curve shows that the higher the expression of LIMK1, the worse the survival of patients with hepatocellular carcinoma (42.2 months vs. 70 months, P = 0.001). Correlation analysis studies have shown that the expression of LIMK1 mRNA in hepatocellular carcinoma is related to immune cell infiltration.Conclusion: Up-regulation of LIMK1 may affect the survival rate and immune invasion of hepatocellular carcinoma. Studies have shown that LIMK1 may be related to the poor prognosis of hepatocellular carcinoma, and has a certain relationship with the immune infiltration of hepatocellular carcinoma.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5110
Author(s):  
Jaehyung Kim ◽  
Soo Young Kim ◽  
Shi-Xun Ma ◽  
Seok-Mo Kim ◽  
Su-Jin Shin ◽  
...  

In most cases, papillary thyroid cancer (PTC) is highly curable and associated with an excellent prognosis. Yet, there are several clinicopathological features that lead to a poor prognosis, underscoring the need for a better genomic strategy to refine prognostication and patient management. We hypothesized that PPARγ targets could be potential markers for better diagnosis and prognosis due to the variants found in PPARG in three pairs of monozygotic twins with PTC. Here, we developed a 10-gene personalized prognostic index, designated PPARGi, based on gene expression of 10 PPARγ targets. Through scRNA-seq data analysis of PTC tissues derived from patients, we found that PPARGi genes were predominantly expressed in macrophages and epithelial cells. Machine learning algorithms showed a near-perfect performance of PPARGi in deciding the presence of the disease and in selecting a small subset of patients with poor disease-specific survival in TCGA-THCA and newly developed merged microarray data (MMD) consisting exclusively of thyroid cancers and normal tissues.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Junliang Zhou ◽  
Mingyan Zhang ◽  
Huanhuan Dong ◽  
Meiqi Wang ◽  
Yue Cheng ◽  
...  

The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients.


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