Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation

Abstract Background Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. Methods Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan–Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). Results SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297–2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = − 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. Conclusion Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

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Long Noncoding RNA RP11-357H14.17 Plays an Oncogene Role in Gastric Cancer by Activating ATF2 Signaling and Enhancing Treg Cells

BioMed Research International ◽

10.1155/2021/6635936 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Tang Xiaoli ◽

Wang Wenting ◽

Zhang Meixiang ◽

Zuo Chunlei ◽

Hu Chengxia

Keyword(s):

Gastric Cancer ◽

Noncoding Rna ◽

Prognostic Value ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Treg Cells ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Biological Behavior

Background. Gastric cancer (GC) is one of the most common malignant tumors in the world. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in GC development are still unclear. It is of great significance to explore the prognostic value of LncRNA signatures for GC. Methods. LncRNAs differently expressed in GC and their prognostic value were studied based on The Cancer Genome Atlas (TCGA) database. The functional regulatory network and immune infiltration of RP11-357H14.17 were further studied using a variety of bioinformatics tools and databases. Results. We found that the high expression of RP11-357H14.17 was closely associated with shortened overall survival (OS) and poor prognosis in gastric cancer patients. We also found that its expression was related to clinical features including tumor volume, metastasis, and differentiation. Functional enrichment analysis revealed that RP11-357H14.17 is closely related to enhanced DNA replication and metabolism; ssGSEA analysis implied the oncogenic roles of RP11-357H14.17 was related to ATF2 signaling and Treg cell differentiation. Furthermore, we verified such link by using real-time PCR and IHC staining in human GC samples. Conclusion. We demonstrate that RP11-357H14.17 may play a crucial role in the occurrence, development, and malignant biological behavior of gastric cancer as a potential prognostic marker for gastric cancer.

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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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Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

Pathophysiology ◽

10.3390/pathophysiology28010003 ◽

2021 ◽

Vol 28 (1) ◽

pp. 20-33

Author(s):

Lydia-Eirini Giannakou ◽

Athanasios-Stefanos Giannopoulos ◽

Chrissi Hatzoglou ◽

Konstantinos I. Gourgoulianis ◽

Erasmia Rouka ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Cell Junctions ◽

Respiratory Pathogens ◽

Gram Negative ◽

Human Proteins ◽

Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

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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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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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Comprehensive Profile Analysis of Differentially Expressed circRNAs in Glucose Deprivation-Induced Human Nucleus Pulposus Cell Degeneration

BioMed Research International ◽

10.1155/2021/4770792 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Hongze Chang ◽

Hongzhang Wang ◽

Xiaolong Yang ◽

Kemin You ◽

Mingwei Jiang ◽

...

Keyword(s):

Intervertebral Disc ◽

Nucleus Pulposus ◽

Enrichment Analysis ◽

Nucleus Pulposus Cell ◽

Glucose Deprivation ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Cell Degeneration

Nucleus pulposus (NP) is the core substance to maintain the homeostasis of intervertebral disc and stability of biomechanics. The insufficient supply of nutrition (especially glucose) is an important factor that leads to the degeneration of NP cells. circRNAs play an important role in the process of intervertebral disc degeneration (IDD) by regulating the functions of NP cells. However, glucose deprivation-related circRNAs and their functions in IDD have not been reported. In this study, the differentially expressed circRNAs in NP cells after 0, 6, 12, and 24 h of glucose deprivation culture were detected by a microarray assay. Besides, time series clustering analysis by STEM software obtained the differentially up- and downregulated circRNAs during glucose deficiency. Then, the main functions and pathways of up- and downregulated circRNAs were predicted by the functional enrichment analysis. By constructing the circRNA-miRNA regulatory network, the potential mechanisms of the most differentially expressed circRNAs were predicted. In addition, according to in vitro validation, circ_0075062 was upregulated in degenerating NP tissues and glucose deprivation-induced NP cell degeneration. Based on Sanger sequencing and RNase tolerance assay, circ_0075062 was the circular transcript. Interfering with circ_0075062 expression could potentially alleviate the imbalance of extracellular matrix (ECM) synthesis and degradation in the NP cells induced by glucose deprivation. Together, these findings help us gain a comprehensive understanding of the underlying mechanisms of IDD, and circ_0075062 may be a promising therapeutic target of IDD.

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Identify Molecular Mechanisms of Jiangzhi Decoction on Nonalcoholic Fatty Liver Disease by Network Pharmacology Analysis and Experimental Validation

BioMed Research International ◽

10.1155/2020/8829346 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Lei Wang ◽

Yin Zhi ◽

Ying Ye ◽

Miao Zhang ◽

Xing Ma ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver Disease ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Active Ingredients ◽

Nonalcoholic Fatty Liver ◽

The Core

Background. Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against nonalcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study is aimed at identifying the core molecular mechanisms of JZD against NAFLD. Methods. The active ingredients were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Traditional Chinese Medicine Integrated Database (TCMID). The targets of those ingredients were identified using ChemMapper database based on 3D structure similarity. NAFLD-related genes were searched from DisGeNET database and Gene Expression Omnibus (GEO) database. Then, we performed protein-protein interaction (PPI) analysis, functional enrichment analysis, and constructed pathway networks of “herbs-active ingredients-candidate targets” and identified the core molecular mechanisms and key active ingredients in the network. Also, molecular docking was carried out to predict the ligands of candidate targets using SwissDock. Finally, the human hepatic L02 cell line was used to establish the NAFLD model in vitro. The effect and key molecules were validated by Oil Red O staining, biochemical assays, and quantitative real-time PCR (qRT-PCR). Results. We found 147 active ingredients in JZD, 1285 targets of active ingredients, 401 NAFLD-related genes, and 59 overlapped candidate targets of JZD against NAFLD. 22 core targets were obtained by PPI analysis. Finally, nuclear receptor transcription and lipid metabolism regulation were found as the core molecular mechanisms of JZD against NAFLD by functional enrichment analysis. The candidate targets PPARα and LXRα were both docked with hyperin as the most favorable interaction, and HNF4α was docked with linolenic acid ethyl ester. According to in vitro experiments, it was found that JZD had an inhibitory effect on lipid accumulation and regulatory effects on cholesterol and triglycerides. Compared with OA group, the mRNA expression levels of PPARα and HNF4α were significantly upregulated in JZD group ( P < 0.05 ), and LXRα was significantly downregulated ( P < 0.001 ). Conclusion. JZD might alleviate hepatocyte steatosis by regulating some key molecules related to nuclear receptor transcription and lipid metabolism, such as PPARα, LXRα, and HNF4α. Our study will provide the scientific evidences of the clinical efficacy of JZD against NAFLD.

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DNAJC10 Correlates with Tumor Immune Characteristics and Predicts the Prognosis of Glioma Patients

10.21203/rs.3.rs-761056/v1 ◽

2021 ◽

Author(s):

Feng Liu ◽

Zewei Tu ◽

Junzhe Liu ◽

Xiaoyan Long ◽

Bing Xiao ◽

...

Keyword(s):

T Cell ◽

Immune Cell ◽

Cox Regression ◽

Predictive Accuracy ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Time Dependent ◽

Prognostic Role

Abstract Background: A role of DNAJC10 has been reported in several cancers, but its function in glioma is not clear. The purpose of this study was to investigate the prognostic role and the underlying functions of DNAJC10 in glioma.Methods: Reverse transcription and quantitative polymerase chain reaction and western blotting were performed to quantify the relative DNAJC10 mRNA and protein expressions of clinical samples. Wilcoxon rank sum tests were used to compare DNAJC10 expression between or among glioma subgroups with different clinicopathological features. The overall survival (OS) rates of glioma patients with different DNAJC10 expression were compared with the Kaplan-Meier method (two-sided log-rank test). The prognosis-predictive accuracy of the DNAJC10 was evaluated by time-dependent receiver operating characteristic (ROC) curves. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations were conducted using the “clusterProfiler” package. Single-sample gene set enrichment analysis was used to estimate immune cell infiltrations and immune-related function levels. The independent prognostic role of DNAJC10 was determined by univariate and multivariate Cox regression analyses. A DNAJC10-based nomogram model was established using multivariate Cox regression in the R package “rms.” Results: Higher DNAJC10 expression was observed in gliomas. It was upregulated in tumors with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, 1p/19q non-co-deletion, and methylguanine-DNA methyltransferase unmethylated gliomas. Patients with gliomas with higher DNAJC10 expression had poorer prognoses than those with low-DNAJC10 gliomas. The predictive accuracy of 1/3/5-year OS of DNAJC10 was stable and robust using a time-dependent ROC model. Functional enrichment analysis recognized that T cell activation and T cell receptor signaling were enriched in higher DNAJC10 gliomas. Immune cell and stromal cell infiltrations, tumor mutation burden, copy number alteration burden, and immune checkpoint genes were also positively correlated with glioma DNAJC10 expression. A DNAJ10-based nomogram model was established and showed strong prognosis-predictive ability.Conclusion: Higher DNAJC10 expression correlates with poor prognosis of patients with glioma and is a potential and useful prognostic biomarker.

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

10.21203/rs.3.rs-546911/v1 ◽

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.

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