scholarly journals TSHZ3 is A Prognostic Biomarker with Immune Infiltration in Stomach Adenocarcinoma and Bladder Urothelial Carcinoma

2020 ◽  
Author(s):  
Xi Zhang ◽  
Ming Wang ◽  
Han-qi Lu ◽  
Qiu-xing He ◽  
Yan-ting You ◽  
...  

Abstract Background: This study aimed to investigate the expressions of Teashirt zinc finger homeobox 3 (TSHZ3) in different cancer types and identify the cancers of which prognosis can be predicted by TSHZ3 expression. Furthermore, we aimed to explore the correlations between tumor-infiltrating immune cells (TIICs) and TSHZ3 expression in these cancers.Methods: TSHZ3 expression was analyzed by the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA). We examined the influence of TSHZ3 on the clinical prognosis with Kaplan-Meier plotter and TIMER (Tumor Immune Estimation Resource). The correlations between tumor immune infiltrates and TSHZ3 expressions were investigated with TIMER and validated by GEPIA.Results: TSHZ3 expressions were significantly higher in stomach adenocarcinoma (STAD) and bladder urothelial carcinoma (BLCA) when compared to normal tissues. Survival analysis results showed that high TSHZ3 expression was correlated with poor overall survival (OS) in STAD and BLCA. The infiltrations of pro-tumorigenic TIICs (M2 macrophages, monocytes, B cells and pDCs) were positively correlated with TSHZ3 expression in STAD and BLCA. Besides, the infiltration of other pro-tumorigenic TIICs (tumor-associated macrophages (TAMs), Th2 cells and Tregs) and expression of T cell exhaustion markers (PD-1 and TIM-3) were positively correlated with TSHZ3 expression in STAD.Conclusions: TSHZ3 expression was up-regulated in STAD and BLCA. High TSHZ3 expression predicted poor prognosis of patients with STAD or BLCA. In addition, TSHZ3 expression potentially contributes to the increased infiltrations of pro-tumorigenic TIICs. TSHZ3 can be used as a prognostic biomarker for predicting prognosis and immune infiltration in STAD and BLCA.

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

Abstract Background 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. Methods 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 COL5A3mRNA expression and immune infiltration. Results 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 COL5A3mRNA was related to immune cell infiltration. Conclusion 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.


2020 ◽  
Vol 7 ◽  
Author(s):  
Aizhai Xiang ◽  
Xia Lin ◽  
Lvping Xu ◽  
Honggang Chen ◽  
Jufeng Guo ◽  
...  

BackgroundThe exact biological role of PCOLCE was not yet clear and there were few reports study the correlation of PCOLCE gene expression level with the occurrence and development of gastric cancer.MethodsThe expression of PCOLCE was analyzed by performing the Oncomine and Ualcan database. We evaluated the function of PCOLCE on clinical prognosis with the use of Kaplan–Meier plotter database. The relationship between PCOLCE and cancer immune in filtrates was researched by Tumor Immune Estimation Resource (TIMER) site database.ResultsPCOLCE significantly upregulated in gastric cancer patients compared to normal gastric samples. And the increased expression of PCOLCE mRNA was closely linked to shorter overall survival (OS), progress-free survival (PFS) in all gastric cancers. Besides, PCOLCE expression displayed a tight correlation with infiltrating levels of macrophages and dendritic cells (DCs) in gastric cancer. Moreover, PCOLCE expression was positively correlated with diverse immune marker sets in gastric cancer.ConclusionAll the results above suggested that overexpression of PCOLCE indicated unfavorable prognosis in patients with gastric cancer. PCOLCE was correlated with immune infiltrating levels including those of B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and DCs in gastric cancer patients. All the findings suggested that PCOLCE could be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric cancer. Additionally, PCOLCE expression potentially contributed to the regulation of monocyte, M2 macrophage, Tfh, CD8 + T cell, TAM, Th1 cell Thus PCOLCE is a potential target for gastric cancer therapy and these preliminary findings require further study to determine whether PCOLCE-targeting reagents might be developed for clinical application in gastric cancer.


2022 ◽  
Author(s):  
Shimao Song ◽  
Xinzhou Deng ◽  
Jincheng Wang ◽  
Jiahui Han ◽  
Zhen Peng ◽  
...  

Abstract Background: GRAP2 is an adaptor protein involved in leukocyte-specific protein-tyrosine kinase signaling; however, the prognostic value of GRAP2 and its correlation with immune cell infiltration in lung adenocarcinoma (LUAD) remain unclear.Methods: All original data were downloaded from the TCGA database and integrated via R 3.2.2. GRAP2 expression was explored with the TCGA and TIMER databases. We evaluated the influence of GRAP2 on clinical prognosis using the Kaplan-Meier plotter, Gene Expression Omnibus (GEO) database and GEPIA database. Correlations between GRAP2 and cancer immune characteristics were analyzed via TIMER and TISIDB databases. Finally, we confirmed the expression of GRAP2 in LUAD by immunohistochemistry staining.Results: Transcription levels of GRAP2 were significantly lower in several human cancers, including LUAD, than in adjacent normal tissues. We also found that tumor tissues have lower protein expression levels of GRAP2 compared with adjacent normal tissues in LUAD by immunohistochemistry staining. The down-regulated GRAP2 was associated with poorer overall survival, pathologic stage, T stage, N stage and primary therapy outcome in LUAD. Mechanically, we identified a hub gene that included a total of 91 GRAP2 co-expressed genes, which were tightly associated with immune response in LUAD. GRAP2 expression was positively correlated with infiltrating levels of B cells, CD8+ T cells, dendritic cells, eosinophils, macrophages, mast cells, Th2 cells, Th1 cells, Th17 cells, NK cells and neutrophils. GRAP2 expression level also affected the cumulative survival time of B cells and dendritic cells. GRAP2 expression is positively correlated with multiple immune markers, chemokines, chemokine receptors and MHC molecules of LUAD.Conclusions: These findings suggest that GRAP2 is a tumor suppressor gene and can be used as a prognostic biomarker for determining prognosis and immune infiltration in LUAD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mali Chen ◽  
Lili Zhang ◽  
Xiaolong Liu ◽  
Zhen Ma ◽  
Ling Lv

Background: Period circadian protein homolog 1 (PER1) is an important component of the biorhythm molecular oscillation system and plays an important part in the development and progression of mammalian cancer. However, the correlations of PER1 with prognosis and tumor-infiltrating lymphocytes in ovarian cancer (OV) remain unclear.Methods: The Oncomine and TIMER databases were used to examine the expression of PER1 in OV. Kaplan–Meier Plotter and PrognoScan were used to evaluate the relationship between PER1 and prognosis. Kaplan–Meier Plotter was used to analyze the relationships between PER1 and clinicopathological features of OV patients. The relationship between PER1 expression and immune infiltration in OV was investigated using the TIMER database and CIBERSORT algorithm. The STRING database was used to analyze PER1-related protein functional groups, the GeneMANIA online tool was used to analyze gene groups with similar functions to those of PER1, and Network Analyst was used to identify transcription factors that regulate PER1. The correlation between PER1 and immunoinvasion of OV was analyzed using TIMER. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect PER1 expression.Results: PER1 was differentially expressed in different cancer tissues, and its expression in various OV subtypes was lower than that in normal ovarian tissue. OV patients with low PER1 expression had a reduced overall survival rate. Decreased PER1 expression in stage 1 and stage 1+2 OV patients was related to poor prognosis, while increased PER1 expression in stage 3+4 patients and TP53 mutation were related to poor overall survival and progression-free survival. We identified eight genes whose expression was strongly correlated with that of PER1, as well as four transcription factors that regulate PER1. In OV, PER1 expression levels were positively correlated with infiltration levels of cells including neutrophils, regulatory T cells, and M2 macrophages, and closely related to a variety of immune markers. Reduced expression of PER1 was significantly associated with poor overall survival.Conclusion: These findings suggest that PER1 could be used as a prognostic biomarker to determine prognosis and immune infiltration in OV patients.


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.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7836 ◽  
Author(s):  
Rui Zhu ◽  
Xin Yang ◽  
Wenna Guo ◽  
Xin-Jian Xu ◽  
Liucun Zhu

Background Bladder cancer is one of the most common cancers, and its histopathological type is mainly bladder urothelial carcinoma, accounting for about 90%. The prognostic biomarkers of bladder cancer are classified into clinical features biomarkers and molecular biomarkers. Nevertheless, due to the existence of individual specificity, patients with similar pathological characteristics still have great differences in the risk of disease recurrence. Therefore, it is often inaccurate to predict the survival status of patients based on clinical characteristic biomarkers, and a prognostic molecular biomarker that can grade the risk of bladder cancer patients is needed. Methods A total of three bladder urothelial carcinoma datasets were used in this study from the Cancer Genome Atlas database and Gene Expression Omnibus database. In order to avoid overfitting, all samples were randomly divided into one training set and three validation sets, which were used to construct and test the prognostic biomarker model of bladder urothelial carcinoma. Univariate and multivariate Cox regression were used to screen candidate mRNAs and construct prognostic biomarkers model. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model. Results A prognostic biomarker model of bladder urothelial carcinoma combining with eight mRNA was constructed. Kaplan–Meier analyses indicated that a significant difference in the survival time of patients between the high-risk and the low-risk group. The area under the ROC curve were 0.632 (95% confidence interval (CI) [0.541–0.723]), 0.693 (95% CI [0.601–0.784]) and 0.686 (95% CI [0.540–0.831]) when the model was used to predict the patient’s survival time in three validation datasets. The model showed high accuracy and applicability.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lingkai Meng ◽  
Ling Ding ◽  
Yue Yu ◽  
Wang Li ◽  
Tao Huang

Background. Stomach adenocarcinoma (STAD) is one of the most common malignant tumors. The Janus kinases (JAKs) play a significant part in cellular biological process, inflammation, and immunity. The roles of JAKs in STAD are still not systematically described. Methods. A series of bioinformatics tools were used to clarify the role of JAKs in STAD. Results. JAK3/TYK2 levels were significantly increased in STAD during subgroup analyses based on gender, tumor grade, cancer stages, and nodal metastasis status. STAD patients with high levels of JAK3/TYK2 had poor overall survival, postprogression survival, and first progression. Immune infiltration revealed a significant correlation between JAK3/TYK2 expression and the abundance of immune cells as well as immune biomarker expression in STAD. JAK3/TYK2 was associated with the adaptive immune response, chemokine signaling pathway, and JAK-STAT signaling pathway. Conclusions. JAK3 and TYK2 serve as prognostic biomarkers and are associated with immune infiltration in STAD.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuxiong Zeng ◽  
Xiaowen Yu ◽  
Chong Ma ◽  
Ruixiang Song ◽  
Zhensheng Zhang ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Jiating Su ◽  
Yushi Zheng ◽  
Fangfang Huang ◽  
Riming Huang ◽  
...  

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer with a relatively poor prognosis, requiring novel therapeutic approaches. Great advances in new immunotherapy strategies have shown encouraging results in lung cancer patients. This study is aimed at elucidating the function of SLC2A5 in the prognosis and pathogenesis of LUAD by analyzing public databases. The differential expression of SLC2A5 in various tissues from Oncomine, GEPIA, and other databases was obtained, and SLC2A5 expression at the protein level in normal and tumor tissues was detected with the use of the HPA database. Then, we used the UALCAN database to analyze the expression of SLC2A5 in different clinical feature subgroups. Notably, in both PrognoScan and Kaplan-Meier plotter databases, we found a certain association between SLC2A5 and poor OS outcomes in LUAD patients. Studies based on the TIMER database show a strong correlation between SLC2A5 expression and various immune cell infiltrates and markers. The data analysis in the UALCAN database showed that the decreased promoter methylation level of SLC2A5 in LUAD may lead to the high expression of SLC2A5. Finally, we used the LinkedOmics database to evaluate the SLC2A5-related coexpression and functional networks in LUAD and to investigate their role in tumor immunity. These findings suggest that SLC2A5 correlated with immune infiltration can be used as a candidate diagnostic and prognostic biomarker in LUAD patients.


2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary feature is the calcium sensor in vesicle transport and exocytosis. SYT4 is one of them, but the relationship between SYT4 and cancer remains unclear. We aim to explore the prognosis and immune function of SYT4 in gastric cancer and low-grade glioma. Methods These databases were used to study the immunological and prognostic role of SYT4 in cancers, including the Oncomine database, Kaplan-Meier plotter, GEPIA2, TIMER, and CGGA. Results The study suggested that the expression levels of SYT4 were lower in both gastric cancer and glioma, compared to the normal tissues. And SYT4 played a protective and harmful role in low-grade gliomas and gastric cancer, respectively. Moreover, we found that a difference between SYT4 expression and the levels of immune infiltration in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). Besides, after exploring the association between the expression levels of SYT4 and markers of immune cells in these two cancers, we found that markers of monocytes, M1/ M2, tumor-associated macrophages (TAMs), Treg cells and SYT4 expressions had an opposite correlation in STAD and LGG. Conclusions SYT4 had an effect on the prognosis of gastric cancer and glioma patients and was related to immune infiltration by regulating TAMs and Treg cells. SYT4 can be used as a prognostic biomarker for STAD and LGG.


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