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

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.

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SPP1 is a Prognostic Related Biomarker and Correlated with Tumor-Infiltrating Immune Cells in Hepatocellular Carcinoma

10.21203/rs.3.rs-1156469/v1 ◽

2021 ◽

Author(s):

Xiaofeng Wang ◽

Kun Zhang ◽

Li Geng ◽

DongLi Liu

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Immune Cell ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Tumor Promoter ◽

Immune Infiltration ◽

Kaplan Meier ◽

Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) functions as a tumor promoter in varies tumors, but little is known whether it is an actual player on driving immune infiltration in hepatocellular carcinoma. Methods: In this study, we identified the expression of SPP1 by Oncomine, GEPIA and TIMER databases, and assessed SPP1 immumohistochemical staining analysis by The HPA database. We evaluated the clinical outcomes between SPP1 expression and hepatocellular carcinoma patients via Kaplan-Meier Plotter. We also tested the relationship between SPP1 and critical oncogenes by TIMER and GEPIA databases. Then we explored immune infiltration analyses using TIMER and TISIDB datasets. In addition, we performed functional enrichment analyses with Metascape and GeneMANIA databases. Results: We found that SPP1 overexpressed in hepatocellular carcinoma tissues and high SPP1 expression was correlated with shorter OS and PFS survivals in hepatocellular carcinoma patients. SPP1 expression is positive correlation with critical oncogenes related stemness associated genes, cell cycle and proliferation, therapeutic resistance, metastasis, and tumor angiogenesis in hepatocellular carcinoma. Importantly, 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 hepatocellular carcinoma. Notably, 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 hepatocellular carcinoma.

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

Cancer Cell International ◽

10.1186/s12935-020-01602-3 ◽

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.

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Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.736367 ◽

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.

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Bioinformatics analysis of the differentially co-expressed genes and immune cell infiltration features associated with pulmonary arterial hypertension

Archives of Medical Science ◽

10.5114/aoms/142102 ◽

2021 ◽

Author(s):

Wenshi Liu ◽

Dongdong Zheng ◽

Wenjing Lv ◽

Ying Hua ◽

Rong Huang ◽

...

Keyword(s):

Immune Cell ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Cell Infiltration ◽

Integrin Subunit ◽

Immune Cell Infiltration ◽

Control Groups ◽

Immune Infiltration ◽

And Control

IntroductionThis study aimed to identify novel differentially co-expressed genes and to investigate the features of immune cell infiltration in PAH.Material and methodsThe GSE113439 and GSE117261 datasets were acquired from the Gene Expression Omnibus database. And the differentially expressed genes between PAH and control groups were identified based on the GSE117261 dataset. Weighted Gene Co-Expression Network Analysis (WGCNA) was adopted to analyze the pre-processed data. Functional enrichment analysis was then carried out to explore the biological functions of these genes modules. The differentially co-expressed key genes modules were in-depth verified by GEO2R analysis. The immune infiltration in PAH was investigated by Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT).ResultsWGCNA analysis found 15 differentially co-expressed genes modules, amongst which module blue indicated that it exhibited the strongest positive link to PAH, whereas module green presented the strongest negative association with PAH. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes in module blue were largely enriched in Lysosome, Complement, and coagulation cascades, and others, while the genes in module green were primarily enriched in the Chemokine signaling pathway, Platelet activation, etc. Integrin subunit alpha M (ITGAM) was identified as the differentially co-expressed key gene. Immune infiltration analysis by CIBERSORT showed that the differences between PAH and control groups or between PAH subgroups.ConclusionsITGAM was considered a promising biomarker to discriminate PAH from the control. Obvious differences were observed in immune infiltration between patients with PAH and normal groups.

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Identification of Prognostic Biomarker and Immune Infiltration of CDH23 in Acute Myeloid Leukemia

10.21203/rs.3.rs-969962/v1 ◽

2021 ◽

Author(s):

Jiao Yang ◽

Fei Lu ◽

Guangxin Ma ◽

Yihua Pang ◽

Yanan Zhao ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Tumor Immunity ◽

Myeloid Leukemia ◽

Immune Cell ◽

Function Analysis ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Immune Infiltration ◽

Acute Myeloid

Abstract Background: Cadherin-23 (CDH23), which plays an important role in intercellular adhesion, is involved in the progression of several types of cancer. However, the biological functions and impact of CDH23 expression on the prognosis of patients with acute myeloid leukemia (AML) are yet to be explored. Herein, we aim to characterize the role and molecular functions of CDH23 in AML.Methods: The expression level of CDH23 were assessed in patients with AML by Gene Expression Profiling Interactive Analysis (GEPIA). The prognostic value of CDH23 was analyzed via GEPIA and LinkedOmics. Correlation analysis and biology function analysis were conducted by LinkedOmics and GeneMANIA database. Relationship of CDH23 with immune infiltration level was detected by TIMER. Results: In the present study, aberrant overexpression of CDH23 was first confirmed in patients with AML and contributed to poor prognosis. Notably, we observed a negative correlation between CDH23 mRNA expression and immune cell infiltration by calculating the ESTIMATE score. In addition, functional enrichment analysis confirmed that CDH23 plays a crucial role in tumor immunity. Conclusions: Our findings indicate that upregulation of CDH23 expression corresponded to shortened overall survival of patients with AML. CDH23 may be involved in mediating tumor immunity, and this highlights the potential of CDH23 as a therapeutic target in AML.

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Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network

Journal of Immunology Research ◽

10.1155/2020/7503605 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Xiang Qian ◽

Zhuo Chen ◽

Sha Sha Chen ◽

Lu Ming Liu ◽

Ai Qin Zhang

Keyword(s):

Expression Profiles ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Ductal Adenocarcinoma ◽

Network Pharmacology ◽

Active Ingredients ◽

Kaplan Meier ◽

Human Protein Atlas

The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.

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Identification of nine key genes by bioinformatics analysis for predicting poor prognosis in smoking-induced lung adenocarcinoma

Lung Cancer Management ◽

10.2217/lmt-2020-0009 ◽

2020 ◽

Vol 9 (2) ◽

pp. LMT30

Author(s):

Chuanli Ren ◽

Weixiu Sun ◽

Xu Lian ◽

Chongxu Han

Keyword(s):

Lung Adenocarcinoma ◽

Differentially Expressed Genes ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Kaplan Meier ◽

Key Genes ◽

Core Genes

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.

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

10.21203/rs.3.rs-117485/v1 ◽

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.

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CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family

10.21203/rs.3.rs-40048/v1 ◽

2020 ◽

Author(s):

Peipei Gao ◽

Ting Peng ◽

Canhui Cao ◽

Shitong Lin ◽

Ping Wu ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Tumor Microenvironment ◽

Immune Cells ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Markers ◽

Immune Infiltration ◽

Kaplan Meier ◽

The Relationship

Abstract Background: Claudin family is a group of membrane proteins related to tight junction. There are many studies about them in cancer, but few studies pay attention to the relationship between them and the tumor microenvironment. In our research, we mainly focused on the genes related to the prognosis of ovarian cancer, and explored the relationship between them and the tumor microenvironment of ovarian cancer.Methods: The cBioProtal provided the genetic variation pattern of claudin gene family in ovarian cancer. The ONCOMINE database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to exploring the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via Kaplan-Meier plotter. Immunologic signatures were enriched by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor microenvironment of ovarian cancer were investigated via Tumor Immune Estimation Resource (TIMER).Results: In our research, claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, we found that CLDN3, CLDN4, CLDN6, CLDN10, CLDN15 and CLDN16 were significantly correlated with overall survival of patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunologic signatures about B cell, CD4 T cell and CD8 T cell. What makes more sense is that CLDN6 and CLDN10 were found related to the tumor microenvironment. CLDN6 expression was negatively correlated with immune infiltration level in ovarian cancer, and CLDN10 expression was positively correlated with immune infiltration level in ovarian cancer. Further study revealed the CLDN6 expression level was negatively correlated with gene markers of various immune cells in ovarian cancer. And, the expression of CLDN10 was positive correlated with gene markers of immune cells in ovarian cancer.Conclusions: CLDN6 and CLDN10 were prognostic biomarkers, and correlated with immune infiltration in ovarian cancer. Our results revealed new roles for CLDN6 and CLDN10, and they were potential therapeutic targets in the treatment of ovarian cancer.

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

10.21203/rs.3.rs-716693/v1 ◽

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.

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