scholarly journals COL5A3 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Pancreatic Cancer

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 ◽  
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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guojun Lu ◽  
Ying Zhou ◽  
Chenxi Zhang ◽  
Yu Zhang

BackgroundProtein-coding gene LIM Domain Kinase 1 (LIMK1) is upregulated in various tumors and reported to promote tumor invasion and metastasis. However, the prognostic values of LIMK1 and correlation with immune infiltrates in lung adenocarcinoma are still not understood. Therefore, we evaluated the prognostic role of LIMK1 and its correlation with immune infiltrates in lung adenocarcinoma.MethodsTranscriptional expression profiles of LIMK1 between lung adenocarcinoma tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA). The LIMK1 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas. Receiver operating characteristic (ROC) curve was used to differentiate lung adenocarcinoma from adjacent normal tissues. Kaplan-Meier method was conducted to assess the effect of LIMK1 on survival. Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analyses were performed using the “ClusterProfiler” package. The relationship between LIMK1 mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).ResultsThe expression of LIMK1 in lung adenocarcinoma tissues was significantly upregulated than those in adjacent normal tissues. Increased LIMK1 mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that with a cutoff level of 4.908, the accuracy, sensitivity, and specificity for LIMK1 differentiate lung adenocarcinoma from adjacent controls were 69.5, 93.2, and 71.9%, respectively. Kaplan-Meier survival analysis showed lung adenocarcinoma patients with high- LIMK1 had a worse prognosis than those with low- LIMK1 (43.1 vs. 55.1 months, P = 0.028). Correlation analysis indicated LIMK1 mRNA expression was correlated with tumor purity and immune infiltrates.ConclusionUpregulated LIMK1 is significantly correlated with poor survival and immune infiltrates in lung adenocarcinoma. Our study suggests that LIMK1 can be used as a biomarker of poor prognosis and potential immune therapy target in lung adenocarcinoma.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


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.


2021 ◽  
Author(s):  
zhang jing ◽  
Fu xi feng

Abstract Background.The AMIGO2 extracellular domain has a leucine - rich repetitive domain (LRR) and encodes a type 1 transmembrane protein , and is a member of the AMIGO gene family .Although the abnormal expression of AMIGO2 is associated with multiple tumors , the relationship with pancreatic cancer is not clear .Methods.The expression of AMIGO2 mRNA and proteins in pancreatic cancer was analyzed using NCBI GEO database and GEPIA2、Human Protein Atlas database.The RNA sequencing data of pancreatic cancer and clinical data of pancreatic cancer patients in TCGA public database were retrospectively analyzed. AMIGO2 gene expression data and their corresponding clinical information in the sample were analyzed retrospectively. The diagnostic value of AMIGO2 expression in pancreatic cancer patients was determined by receiver operating characteristic (ROC) curve analysis. The effects of AMIGO2 expression differences on survival time of pancreatic cancer patients were analyzed by Kaplan-Meier Plotter database and GEPIA2 database.The correlation between AMIGO2 gene and TP53 mutation in pancreatic cancer was analyzed by UALCAN database and TIMER database. The similar genes of AMIGO2 in pancreatic cancer were analyzed by GEPIA2 database, and the biological behavior, cellular composition, molecular function enrichment analysis and protein interaction of similar genes were analyzed by DAVID database and Metascape database. enrichment analysis of AMIGO2 similar gene pathways using KEGG database. The MSIGDB cancer coexpression module in Harmonizome database and TIMER database were used to study the gene coexpression of AMIGO2 in pancreatic cancer. AMIGO2 transcription factors were predicted using the JASPER database. The pathway of AMIGO2 transcription factors and co-expression genes was studied by KEGG database.Results. The expression of AMIGO2 (GSE16515, GSE15471) in pancreatic cancer tissues was significantly higher than that in normal tissues (P < 0.05). The GEPIA2 database also confirmed that the expression of AMIGO2 in pancreatic cancer tissues was significantly higher than that in normal tissues. The expression level of AMIGO2 gene was correlated with lymph node metastasis and histological grade of pancreatic cancer (P<0.05). The high expression of AMIGO2 protein in pancreatic cancer was confirmed in Human Protein Atlas database. The overall survival rate and progression-free survival rate of pancreatic cancer patients with high expression of AMIGO2 were significantly shorter than those of patients with low expression of AMIGO2 in Kaplan-Meier Plotter database and GEPIA2 database. In the gene ontology analysis, it is found that AMIGO2 is involved in cell adhesion, proliferation, migration, apoptosis and other biological processes. KEGG analysis pathway is concentrated in the focal adhesion pathway, mitotic cell cycle changes, and the regulation of cell protein localization. Abnormal expression of AMIGO2 was found in pancreatic cancer caused by TP53 mutation in UALCAN and TIMER databases.In JASPAR database, we predicted that there are 10 transcription sites between AMIGO2 and transcription factor MYB. In addition, there are positive genes related to AMIGO2 in TIMER database and transcription factor MYB regulates tumor cell proliferation and apoptosis in PI3K-Akt signal transduction pathway and WNT signal pathway in pancreatic cancer.


2021 ◽  
Author(s):  
Min Wang ◽  
Tao Lu ◽  
Yanshi Li ◽  
Min Pan ◽  
Zhihai Wang ◽  
...  

Abstract Background: Head and neck cancer (HNC) are highly aggressive solid tumors with poor prognoses. The tumor microenvironment (TME) plays a critical role in angiogenesis, invasion, and metastasis of HNC. In the TME, immune and stromal cells influence tumor initiation, response, and therapy. Our study aimed to evaluate the progression and prognosis of HNC by analyzing the key genes involved in immunization and stromal cells. Methods: Gene expression profiles, demographics, and survival data were downloaded from the TCGA database. Patients with HNC were divided into high immune/stromal score groupss or low immune/stromal score groups based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified via functional enrichment analysis and protein-protein interaction networks, and survival analysis based on DEGs was also performed.Results: A total of 522 patients with HNC were enrolled for analysis. The average age was 60.87, and one-third of the patients were HPV-positive. Kaplan-Meier survival analysis showed that patients' median survival time in the low-score group was shorter than that of the high-score group (625 vs. 680 days, log-rank, p = 0.1716). According to immune scores, 925 genes were upregulated, and 72 genes were downregulated in the high-score group compared with the low-score group. Top Gene Ontology terms identified that T-cell costimulation, regulation of immune response, and the external side of the plasma membrane were the most involved pathways. Moreover, Kaplan-Meier analysis revealed that 480 DEGs were upregulated in the high-immune scores group, and a total of 126 DEGs were significantly associated with poor survival. Besides, we identified the hub genes of DEGs through protein-protein interactions and found that PTPRC, CD247, and CD4 are associated with immune infiltration and all-cause mortality.Conclusions: We identified a series of TME‐related genes significantly associated with overall mortality; this information is crucial for further understanding the role of TME and immune infiltration in the prognosis of HNC.


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 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Lei Feng ◽  
Yi Wang ◽  
Jiasheng Qin ◽  
Yu Fu ◽  
Zeyi Guo ◽  
...  

Background. Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods. Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results. The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions. These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Rong Ma ◽  
Yanyun Zhao ◽  
Miao He ◽  
Hongliang Zhao ◽  
Yifan Zhang ◽  
...  

Abstract Background Increasing studies have suggested that aberrant expression of microRNAs might play essential roles in the progression of cancers. In this study, we sought to construct a high-specific and superior microRNAs signature to improve the survival prediction of colon adenocarcinoma (COAD) patients. Methods The genome-wide miRNAs, mRNA and lncRNA expression profiles and corresponding clinical information of COAD were collected from the TCGA database. Differential expression analysis, Kaplan–Meier curve and time-dependent ROC curve were calculated and performed using R software and GraphPad Prism7. Univariate and multivariate Cox analysis was performed to evaluate the prognostic ability of signature. Functional enrichment analysis was analyzed using STRING database. Results We identified ten prognosis-related microRNAs, including seven risky factors (hsa-miR-197, hsa-miR-32, hsa-miR-887, hsa-miR-3199-2, hsa-miR-4999, hsa-miR-561, hsa-miR-210) and three protective factors (hsa-miR-3917, hsa-miR-3189, hsa-miR-6854). The Kaplan–Meier survival analysis showed that the patients with high risk score had shorter overall survival (OS) in test series. And the similar results were observed in both validation and entire series. The time-dependent ROC curve suggested this signature have high accuracy of OS for COAD. The Multivariate Cox regression analysis and stratification analysis suggested that the ten-microRNA signature was an independent factor after being adjusted with other clinical characteristics. In addition, we also found microRNA signature have higher AUC than other signature. Furthermore, we identified some miRNA-target genes that affect lymphatic metastasis and invasion of COAD patients. Conclusion In this study, we established a ten-microRNA signature as a potentially reliable and independent biomarker for survival prediction of COAD patients.


2020 ◽  
Author(s):  
Yi Yang ◽  
Zhenshuang Wang ◽  
Shengrong Long ◽  
Jinhai Huang ◽  
Chengran Xu ◽  
...  

Abstract Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.


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