scholarly journals Comprehensive Analysis of the Prognostic Value and Immune Infiltration of Calpains in Pancreatic Cancer

2021 ◽  
Author(s):  
Lan Chuan ◽  
Haoyou Tang ◽  
Sheng Liu ◽  
Lin Ma ◽  
Yifu Hou
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Surface Receptor ◽  
Cell Junction ◽  
Expression Levels ◽  
Surface Receptor

Abstract Background: Calpains (CAPNs) are intracellular calcium-activated neutral cysteine proteinases that are involved in cancer initiation, progression, and metastasis; however, their role in pancreatic cancer (PC) remains unclear. Methods: We combined data from various mainstream databases (i.e., Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, STRING, GeneMANIA, and ssGSEA) and investigated the role of CAPNs in the prognosis of PC and immune cell infiltration.Results: Our results showed that CAPN1, 2, 4, 5, 6, 8, 9, 10, and 12 were highly expressed in PC. The expression levels of CAPN1, 5, 8, and 12 were positively correlated with the individual cancer stages. Moreover, the expression levels of CAPN1, 2, 5, and 8 were negatively correlated with the overall survival (OS) and recurrence-free survival (RFS); whereas that of CAPN10 was positively correlated with OS and RFS. We found that CAPN1, 2, 5, and 8 were correlated with tumour-infiltrating T follicular helper cells and CAPN10 with tumour-infiltrating T helper 2 cells. Functional enrichment analysis showed that the differentially expressed CAPNs (CAPN1, 2, 5, 8, and 10) are involved in axonogenesis, cell-substrate adhesion, immune response-activating cell surface receptor signalling pathway, and cell junction organisation in PC.Conclusions: These results suggested that CAPN1, 2, 5, 8, and 10 could be used as prognostic biomarkers in PC and can assist in improving individualised treatment strategies.

scholarly journals CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Expression Levels ◽  
T Complex ◽  
Advanced Tumor ◽  
Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

scholarly journals Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11321
Author(s):  
Di Zhang ◽  
Pengguang Yan ◽  
Taotao Han ◽  
Xiaoyun Cheng ◽  
Jingnan Li
Keyword(s):  
Ulcerative Colitis ◽  
Mitochondrial Dysfunction ◽  
Single Gene ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junction ◽  
Biological Processes ◽  
Hub Genes ◽  
Key Genes

Background Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC. Methods Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the “limma” R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the “clusterProfiler” R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene. Results Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3. Conclusions Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.

scholarly journals Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lingling Gao ◽  
Xiao Li ◽  
Qian Guo ◽  
Xin Nie ◽  
Yingying Hao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Cell Junction ◽  
Immune Infiltration ◽  
Potential Biomarker

Abstract Background Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC. Methods The expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry. Results The expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients. Conclusion Members of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.

scholarly journals Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of pancreatic cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Tumor Formation ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Hub Genes ◽  
Cerna Network ◽  
Competing Endogenous Rna Network

Abstract Background It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. Methods We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. Results A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. Conclusion Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

scholarly journals Investigation of Candidate Genes and Mechanism Associated with Immune Cell during the Progression of Glioblastoma based on Bioinformatics

2020 ◽  
Author(s):  
Hui Xie ◽  
Xiao-hui Ding ◽  
Ce Yuan ◽  
Jin-jiang Li ◽  
Zhao-yang Li ◽  
...  
Keyword(s):  
Immune Cell ◽  
Risk Model ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Normal Group ◽  
Functional Enrichment ◽  
M2 Macrophage ◽  
Survival Prognosis ◽  
Cerna Network ◽  
Tumor Group

Abstract Background: This study aimed to investigate the molecular mechanism of immune cell infiltration during the development of glioblastoma multiforme (GBM), and explore the potential immune cell associated prognostic genes for GBM. Methods: Gene expression data and corresponding clinical data of GBM samples (tumor group) and normal samples (normal group) in TCGA-GBM and GTEx dataset were downloaded. The differentially expression analysis was performed on samples between two groups. Based on tumor immune microenvironment analysis, the immune-related RNAs (lncRNAs and mRNAs) were further explored. Then, functional enrichment analysis, ceRNA network, risk prediction model and prognosis investigation were performed. Finally, the results of survival prognosis of key genes were tested by additional datasets. Results: A total of 4989 up-regulated genes and 2349 down-regulated genes were revealed between tumor group and normal group. M2 macrophages accounted for the largest proportion of tumor infiltrates immune cells in GBM, and was related to the prognosis of GBM patients. Totally 168 mRNAs (KIF18B) and 5 lncRNAs were related to infiltration of M2 Macrophage, of which 25 mRNAs and 5 lncRNAs forms a ceRNA network through 37 miRNAs (eg., miR-6849-3p). These genes were mainly assembled in functions like signal release. A risk model based on 5 mRNAs (such as FOX4 and ELFN2) and lncRNA PR11-161H23.5 was constructed. Verification test showed that all 5 mRNAs were significantly associated with OS prognosis.Conclusions: M2 Macrophage infiltration might participate in tumorigenesis of GBM via RP11-161H23.5-miR6849-3p-KIF18B ceRNA interaction. Furthermore, mRNAs such as FOX4 and ELFN2 might be potential prognostic markers for GBM patients.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated With Tumor-Infiltrating Immune Cells in Ovarian Cancer

2021 ◽  
Author(s):  
Wen Gao ◽  
Sheng Yin ◽  
Haiyan Sun ◽  
Zhuyan Shao ◽  
Peipei Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in ovarian cancer. Of particular importance, functional enrichment analysis suggested that SPP1 strong related with immune response.Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer.Trial registration: Not applicable.

scholarly journals Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of Pancreatic cancer

2020 ◽  
Author(s):  
Fuqiang Zu ◽  
Peng Liu ◽  
Huaitao Wang ◽  
Ting Zhu ◽  
Jian Sun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Tumor Formation ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Hub Genes ◽  
Cerna Network ◽  
Competing Endogenous Rna Network

Abstract Background: It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression.Methods: We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC.Results: A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b-/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC.Conclusion: Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b-/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

scholarly journals Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Guofu Lin ◽  
Luyang Chen ◽  
Lanlan Lin ◽  
Hai Lin ◽  
Zhifeng Guo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Functional Enrichment Analysis ◽  
Tumor Stage ◽  
Stage I ◽  
Functional Enrichment ◽  
Gene Expressions ◽  
Kaplan Meier

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

scholarly journals ITGA5 Is a Prognostic Biomarker and Correlated with Immune Infiltration In Gastrointestinal Cancers

2020 ◽  
Author(s):  
Hai Zhu ◽  
Gang Wang ◽  
Haixing Zhu ◽  
Aman Xu
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Th2 Cells ◽  
Integrin Subunit ◽  
Expression Levels ◽  
Immune Infiltration

Abstract Background: Integrin Subunit Alpha 5 (ITGA5) belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal (GI) tumors remain unclear.Methods: The expression levels of ITGA5 were detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2(GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER and immunohistochemistry (IHC) staining were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape.Results: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of GI tumors. In addition, ITGA5 expression levels was significantly associated with tumor purity and immune infiltration levels of different immune cells in GI tumors. Interestingly, Immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 were mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”.Conclutions: our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in GI tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.

scholarly journals Identification of an epithelial-mesenchymal transition-related lncRNA prognostic signature for patients with glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
XinJie Yang ◽  
Sha Niu ◽  
JiaQiang Liu ◽  
Jincheng Fang ◽  
ZeYu Wu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Prognostic Signature ◽  
Mesenchymal Transition

AbstractGlioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan–Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.

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