scholarly journals Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yongdong Guo ◽  
Yutong He

Abstract The solute carrier 30 (SLC30) family genes play a fundamental role in various cancers. However, the diverse expression patterns, prognostic value, and potential mechanism of SLC30A family genes in gastric cancer (GC) remain unknown. Herein, we analyzed the expression and survival data of SLC30A family genes in GC patients using multiple bioinformatic approaches. Expression data of SLC30A family genes for GC patients were extracted from the Cancer Genome Atlas (TCGA) and genetic alteration frequency assessed by using cBioportal database. And validated the expression of SLC30A family genes in GC tissues and corresponding normal tissues. The prognostic value of SLC30A family genes in gastric cancer patients were explored using Kaplan–Meier plotter database. Functional enrichment analysis performed using DAVID database and clusterProfiler package. And ssGSEA algorithm was performed to explore the relationship between the SLC30A family genes and the infiltration of immune cells. We found that the median expression levels of SLC30A1-3, 5–7, and 9 were significantly upregulated in gastric cancer tissues compared to non-cancerous tissues, while SLC30A4 was downregulated. Meanwhile, SLC30A1-7, and 9 were significantly correlated with advanced tumor stage and nodal metastasis status, SLC30A5-7, and 9–10 were significantly related to the Helicobacter pylori infection status of GC patients. High expression of five genes (SLC30A1, 5–7, and 9) was significantly correlated with better overall survival (OS), first progression survival (FPS), and post progression survival (PPS). Conversely, upregulated SLC30A2-4, 8, and 10 expression was markedly associated with poor OS, FP and PPS. And SLC30A family genes were closely associated with the infiltration of immune cells. The present study implied that SLC30A5 and 7 may be potential biomarkers for predicting prognosis in GC patients, SLC30A2 and 3 play an oncogenic role in GC patients and could provide a new strategy for GC patients treatment.

2021 ◽  
Author(s):  
Yuqian Zhou ◽  
HongYi Zhu ◽  
Yi Chu ◽  
Min Luo ◽  
WenYu Li ◽  
...  

Abstract Objectives: Growing evidence suggests that aberrant expression of Karyopherin alpha (KPNA) has been involved in the tumor progression of various cancer types. However, the differential expression patterns and prognostic value of the seven KPNA subtypes remain to be investigated. Hence the transcriptional and survival data of KPNAs in patients with pancreatic adenocarcinoma (PAAD) were analyzed.Methods: Transcriptional and survival data related to KPNA expression in patients with PAAD were derived through ONCOMINE, Gene Expression Profiling Interactive Analysis 2, and Human protein atlas databases. The DNA alteration for KPNAs came from The Cancer Genome Atlas and c-BioPortal. The prognostic value analysis was performed with Kaplan–Meier Plotter. Gene functional enrichment analyses were conducted in database LinkedOmics and Metascape.Results: The mRNA expression levels of KPNA1-4, 6,7 were found significantly upregulated in pancreatic cancer tissues than in normal pancreas tissues, whereas the aberrant expression level of KPNA5 was no more significant in the former than in the latter. KPNA1, 4, and 7 were associated with tumor stage or grade of PAAD. Nevertheless, the obvious association with clinical outcomes was identified only in the aberrant expression of KPNA4. Further gene functional exploration about KPNA4 displayed KPNA4 strongly associated with adherens junction and tumor metastasis in PAAD. Conclusion: Our findings suggested that KPNA4 might be a potential diagnostic and a new biomarker of prognosis for patients with pancreatic adenocarcinoma.


Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu

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.


2021 ◽  
pp. 1-12
Author(s):  
Yanjie You ◽  
Shengjuan Hu

BACKGROUND: We have previously characterized esophageal carcinoma-related gene 4 (ECRG4) as a novel tumor suppressor gene, which is frequently inactivated in nasopharyngeal carcinoma and breast cancer. Nevertheless, the expression status and prognostic significance of ECRG4 maintain elusive in human gastric cancer. Herein, we examined ECRG4 expression profile in gastric cancer and assessed its association with clinicopathological characteristics and patient survival. METHODS: Online data mining, real-time RT-PCR and immunohistochemistry were employed to determined ECRG4 expression at transcriptional and protein levels in tumors vs. noncancerous tissues. Statistical analyses including the Kaplan-Meier survival analysis and the Cox hazard model were utilized to detect the impact on clinical outcome. Moreover, ECRG4 expression was silenced in gastric cancer SGC7901 cells, and cell proliferation, colony formation and invasion assays were carried out. RESULTS: ECRG4 mRNA and protein levels were obviously downregulated in cancer tissues than noncancerous tissues. Statistical analyses demonstrated that low ECRG4 expression was found in 34.5% (58/168) of primary gastric cancer tissues, which was associated with higher histological grade (P= 0.018), lymph node metastasis (P= 0.011), invasive depth (P= 0.020), advanced tumor stage (P= 0.002) and poor overall survival (P< 0.001). Multivariate analysis showed ECRG4 expression is an independent prognostic predictor (P< 0.001). Silencing ECRG4 expression promoted gastric cancer cell growth and invasion. Western blot analysis revealed the anti-metastatic functions of ECRG4 by downregulating of E-cadherin and α-Catenin, as well as upregulating N-cadherin and Vimentin. CONCLUSIONS: Our observations reveal that ECRG4 expression is involved in gastric cancer pathogenesis and progression, and may serve as a candidate prognostic biomarker for this disease.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Tang Xiaoli ◽  
Wang Wenting ◽  
Zhang Meixiang ◽  
Zuo Chunlei ◽  
Hu Chengxia

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Hui Ma ◽  
Zhen Liu ◽  
Honglin Li ◽  
Xuewang Guo ◽  
Sujie Guo ◽  
...  

The minichromosome maintenance complex 3 (MCM3) is essential for the regulation of DNA replication and cell cycle progression. However, the expression and prognostic values of MCM3 in cervical cancer (CC) have not been well-studied. Herein, we investigated the expression patterns and survival data of MCM3 in cervical cancer patients from the ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan-Meier Plotter, and LinkedOmics databases. The expression level of MCM3 is negatively correlated with advanced tumor stage and metastatic status. Specifically, MCM3 is significantly differentially expressed between patients in stage 1 and stage 3 cervical cancer with p value 0.0138. Similarly, the p values between stage 1 and stage 4 cervical cancer, between stage 2 and stage 3, and between stage 2 and stage 4 are 0.00089, 0.0244, and 0.00197, respectively. Not only that, cervical cancer patients with high mRNA expression of MCM3 may indicate longer overall survival but indicate shorter relapse-free survival. PRIM2 and MCM6 are positively correlated genes of MCM3. Bioinformatics analysis revealed that MCM3 might be considered a biological indicator for prognostic evaluation of cervical cancer. However, it is currently limited to bioinformatics analysis, and more clinical tissue specimens and cell experiments are needed to further explore the role of MCM3 in the occurrence and progression of cervical cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yawei Zhang ◽  
Han Wang ◽  
Xiaoyu Xu ◽  
Huifang Liu ◽  
Tengfei Hao ◽  
...  

Immunosuppressive molecules are valuable prognostic biomarkers across different cancer types. Leukocyte immunoglobulin like receptor subfamily B1 (LILRB1) is considered to be an immunosuppressive molecule, which is an important receptor of human leukocyte antigen G. However, the clinical significance of LILRB1 expression in gastric cancer remains unexplored. We analyzed the immunohistochemistry data of 166 gastric cancer patients to determine the clinicopathologic and survival significance of LILRB1. Immunofluorescence was conducted to detect the co-localization of LILRB1 with infiltrating immune cells. Additionally, we also assessed the immune contexture, immune cell functions and tumor microenvironment state related to LILRB1. We found that LILRB1 was mainly present in tumor stroma which was higher in tumor tissues compared with matched adjacent tissues. High-LILRB1 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis showed that LILRB1 had a significant positive correlation with M2 tumor-associated macrophages (TAMs) infiltration. Immunofluorescence confirmed that M2 TAMs were the primary immune cells expressing LILRB1. Dense infiltration of LILRB1+ M2 TAMs yielded an immunosuppressive microenvironment manifested as enriched exhausted CD8+ T cells and increased immunosuppressive cytokines. Moreover, patients with high infiltration of both LILRB1+ cells and M2 TAMs indicated poor prognosis and inferior therapeutic responsiveness to adjuvant chemotherapy. In conclusion, LILRB1+ M2 TAMs were associated with a pro-tumor immune contexture and determine poor prognosis in gastric cancer. Further studies are essential to explore therapeutic targeting LILRB1+ M2 TAMs.


2016 ◽  
Vol 469 (5) ◽  
pp. 505-513 ◽  
Author(s):  
Zhi-Feng Miao ◽  
Xing-Yu Liu ◽  
Hui-Mian Xu ◽  
Zhen-Ning Wang ◽  
Ting-Ting Zhao ◽  
...  

2021 ◽  
Author(s):  
Xin-zhou Huang ◽  
Hui Chen ◽  
Wen-ming Song ◽  
Ying-ying Wang ◽  
Meiyuan Zhou ◽  
...  

Abstract Background: Biglycan (BGN) encodes an extracellular matrix (ECM) proteoglycan. However, the potential diagnostic and prognostic value of BGN in gastric cancer (GC) have not yet been reported. In this analysis, BGN expression in GC was evaluated across the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Oncomine databases, and verified using immunohistochemistry (IHC). The relationship between BGN expression and clinicopathological parameters was assessed by chi-square test and logistic regression. We analyzed the prognostic value of BGN. Then, Gene set enrichment analysis (GSEA) was used to screen the signaling pathways involved in high BGN expression datasets in GC. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in GC tissues, and the correlation between BGN and infiltrating immune cells was analyzed.Results: The results showed that the mRNA levels of BGN were significantly up-regulated in GC compared with normal tissues (all P <0.001). The Kaplan-Meier plotter online database suggested that patients with high BGN expression had a poor prognosis (P=1.3e-10). In addition, using gene sets analysis, we found that pathways of bladder cancer, Wnt-signaling, TGF-beta signaling, and ECM-receptor interaction were differentially activated in high-expression BGN tissues. Furthermore, CIBERSORT analysis for the proportion of TICs revealed that macrophages M2 was positively correlated with BGN expression. Conclusions: In conclusion, BGN can be used as potential diagnostic markers of GC, and immune cell infiltration plays an important role in the occurrence and progression of GC. The finding may have significant implication for the diagnosis, prognosis and treatment of GC.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7821 ◽  
Author(s):  
Xiaoming Zhang ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
Zhengguo He ◽  
Cun Liu ◽  
...  

Background Cumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening. Methods First, the linear fitting method was used to identify differentially expressed genes from the breast cancer RNA expression profiles in The Cancer Genome Atlas (TCGA). Next, the diagnostic value of all differentially expressed lncRNAs was evaluated using a receiver operating characteristic (ROC) curve. Then, the top ten lncRNAs with the highest diagnostic value were selected as core genes for clinical characteristics and prognosis analysis. Furthermore, core lncRNA-mRNA co-expression networks based on weighted gene co-expression network analysis (WGCNA) were constructed, and functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differential expression level and diagnostic value of core lncRNAs were further evaluated by using independent data set from Gene Expression Omnibus (GEO). Finally, the expression status and prognostic value of core lncRNAs in various tumors were analyzed based on Gene Expression Profiling Interactive Analysis (GEPIA). Results Seven core lncRNAs (LINC00478, PGM5-AS1, AL035610.1, MIR143HG, RP11-175K6.1, AC005550.4, and MIR497HG) have good single-factor diagnostic value for breast cancer. AC093850.2 has a prognostic value for breast cancer. AC005550.4 and MIR497HG can better distinguish breast cancer patients in early-stage from the advanced-stage. Low expression of MAGI2-AS3, LINC00478, AL035610.1, MIR143HG, and MIR145 may be associated with lymph node metastasis in breast cancer. Conclusion Our study provides candidate biomarkers for the diagnosis and prognosis of breast cancer, as well as a bioinformatics basis for the further elucidation of the molecular pathological mechanism of breast cancer.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8348
Author(s):  
Mei Chen ◽  
Shufang Zhang ◽  
Xiaohong Wen ◽  
Hui Cao ◽  
Yuanhui Gao

Background Human intracellular chloride channel 3 (CLIC3) is involved in the development of various cancers, but the expression and prognostic value of CLIC3 mRNA in bladder cancer (BC) remain unclear. Methods The gene expression data and clinical information of CLIC3 were obtained from the Gene Expression Omnibus (GEO) database and verified in the Oncomine and The Cancer Genome Atlas (TCGA) database. The expression of CLIC3 mRNA in BC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The Kaplan-Meier method was used to analyze the relationship between the expression of CLIC3 mRNA and the prognosis of BC. Cox univariate and multivariate analyses were performed on the overall survival and tumor-specific survival of BC patients. The genes coexpressed with CLIC3 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). CLIC3-related signal transduction pathways in BC were explored with gene set enrichment analysis (GSEA). Results The expression of CLIC3 mRNA in BC tissues was higher than that in normal tissues (P < 0.01). High CLIC3 mRNA expression was associated with age (P = 0.021) and grade (P = 0.045) in BC patients. High CLIC3 mRNA expression predicted a poor prognosis in BC patients (P < 0.05). Cox univariate and multivariate analyses showed that high CLIC3 mRNA expression was associated with tumor-specific survival in BC patients (P < 0.05). Functional enrichment analyses indicated that CLIC3 may be significantly associated with the cell cycle, focal adhesion, the extracellular matrix (ECM) receptor interaction and the P53 signaling pathway. Conclusions CLIC3 mRNA is highly expressed in BC, and its high expression is related to the adverse clinicopathological factors and prognosis of BC patients. CLIC3 can be used as a biomarker for the prognosis of BC patients.


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