Comprehensive Analysis of Glutamate-Rich WD Repeat-Containing Protein 1 and Its Potential Clinical Significance for Pancancer

Background and Objective. Glutamate-rich WD repeat-containing protein 1 (GRWD1), as a novel CDT1-binding protein, plays a critical role in the initial stage of DNA replication. To date, few studies have shown that GRWD1 is a driving factor for lung cancer, bladder cancer, and colorectal cancer. However, no systematic pancancer analysis has been carried out. This study was aimed at exploring its expression signature, prognostic value, immune infiltration pattern, and biological functions using bioinformatics tools. Methods. The expression level of GRWD1 in human cancer tissues was analyzed using the Tumor Immune Evaluation Resource (ver. 2.0, TIMER2), Gene Expression Profiling Interactive Analysis (ver. 2, GEPIA2), and UALCAN databases. The Kaplan-Meier plotter was utilized to analyze the survival data. Spearman’s correlation analysis was used to find out the correlation between the expression level of GRWD1 and predictive biomarkers, such as tumor mutation burden (TMB) and microsatellite instability (MSI). Furthermore, the MEXPRESS website was used to study the potential relationship between DNA methylation level of GRWD1 and pathological staging. We utilized the “immune” module provided on the TIMER2 website to explore the relationship between the expression level of GRWD1 and immune infiltration in all types of cancer in TCGA. Pearson’s correlation analysis was used to investigate the correlation between the expression level of GRWD1 and the expression levels of immune checkpoint-related genes. For protein expression analysis, we used the CPTAC module provided by the UALCAN portal to compare the total protein and phosphorylated protein level of GRWD1 in adjacent normal and tumor tissues. Results. GRWD1 was overexpressed in tissues of most types of cancer, in which the expression levels of GRWD1 in the kidney chromophobe (KICH), kidney renal papillary cell carcinoma (KIRP), and kidney renal clear cell carcinoma (KIRC) tissues showed an opposite trend, and the expression level of GRWD1 was correlated to only the KIRC tumor stage. The results of survival analysis showed that the expression level of GRWD1 was significantly associated with overall survival in six types of cancer and disease-free survival (DFS) in three types of cancer. Importantly, the increased expression level of GRWD1 was strongly correlated with prognosis of KIRC patients. There was a positive relationship between the expression level of GRWD1 and immune cell infiltration in several types of cancer, and the expression level of GRWD1 was also positively correlated with TMB, MSI, and DNA methylation in some types of cancer. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that “ubiquitin mediated proteolysis,” “spliceosome,” and “nucleotide excision repair” were involved in the effect of GRWD1 expression on tumor pathogenesis. Conclusion. This pancancer analysis provided a comprehensive overview of the carcinogenic effects of GRWD1 on a variety of human cancers. The results of bioinformatics analysis indicated GRWD1 as a promising biomarker for detection, prognosis, and therapeutic assessment of diverse types of cancer, and GRWD1 could act as a tumor suppressor in KIRC.

Download Full-text

Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01889-8 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Wuping Yang ◽

Kenan Zhang ◽

Lei Li ◽

Yawei Xu ◽

Kaifang Ma ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Protein Expression ◽

Cell Carcinoma ◽

Clinical Significance ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Cell Renal Cell Carcinoma ◽

Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

Download Full-text

Identification of ACSL4 as a biomarker and contributor of ferroptosis in clear cell renal cell carcinoma

10.21203/rs.3.rs-24079/v1 ◽

2020 ◽

Author(s):

na guo

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Transfection ◽

Prognostic Significance ◽

Expression Level ◽

Cell Renal Cell Carcinoma ◽

Expression Levels ◽

Protein Ubiquitination

Abstract Background ACSL4 has been reported to be related to tumor genesis and involved in the processes of ferroptosis. However, the expression levels and prognostic value of ACSL4 in clear cell renal cell carcinoma (ccRCC) remain unclear. Methods The Oncomine and TCGA databases were used to predict the expression of ACSL4 mRNA in ccRCC and its association with ccRCC prognosis. The expression levels of ACSL4 were determined in human RCC tissues by real-time PCR. Kaplan-Meier curves were used to analyze the diagnostic and prognostic significance of ACSL4 in ccRCC. A ferroptosis inducer (erastin) was used to investigate the effects of ACSL4 on ferroptosis in ccRCC cell lines. Results The expression level of ACSL4 was significantly down-regulated in ccRCC tissues (P < 0.001), which was consistent with the analysis of the Oncomine and TCGA database. Then, immunohistochemical results demonstrated that the ACSL4 was weak or not detected in ccRCC tissues than that in normal tissues. ACSL4 differential expression level was significantly related to gender, ccRCC subtypes, nodal invasion, tumor grade and cancer stages (all P < 0.001). Survival analysis revealed that overall survival was favorable in ccRCC patients with ACSL4 high expression (P = 0.014). Overexpression of ACSL4 by gene transfection restores ferroptosis sensitization in cancer cells, whereas suppression of ACSL4 expression by RNAi increases ferroptosis resistance. Mechanically, protein ubiquitination may be involved in ACSL4-mediated ferroptosis. Conclusions As a monitor and contributor of ferroptosis, ACSL4 was decreased in ccRCC and served as a useful diagnostic and prognostic biomarker, which will be a new potential therapeutic target for ccRCC.

Download Full-text

DAB2IP Plays Important Clinical Significance and Correlates With Immune Infiltration in Renal Cell Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820936682 ◽

2020 ◽

Vol 19 ◽

pp. 153303382093668

Author(s):

Haoyuan Cao ◽

Jiandong Zhang ◽

Wei Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Messenger Rna ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Interacting Protein ◽

Expression Levels ◽

Immune Infiltration

Background: Disabled homolog 2-interacting protein is a new member of the Ras GTPase superfamily involved in the regulation of cell proliferation, apoptosis, and metastasis. However, the expression of disabled homolog 2-interacting protein in renal cell carcinoma, its correlation with cancer prognosis, and tumor infiltrating lymphocytes remains unclear. Methods: The expression of disabled homolog 2-interacting protein was analyzed by UALCAN database, GEPIA database and the evaluation of disabled homolog 2-interacting protein effects on clinical prognosis. Prognostic factor analysis was used to identify the correlations between disabled homolog 2-interacting protein and cancer immune infiltration via the TIMER database. In addition, COXPRESdb database was used to analyze the enrichment of disabled homolog 2-interacting protein co-expression genes. Results: Compared to the normal tissues, the messenger RNA expression levels of DAB2IP are higher in 8 while lower in 15 types of tumor tissues. Furthermore, disabled homolog 2-interacting protein has high expression in kidney chromophobe and low expression in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The messenger RNA expression levels of disabled homolog 2-interacting protein decrease gradually due to the increasing tumor staging which positively correlates with disease-free survival and overall survival in both kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. The expression levels of disabled homolog 2-interacting protein also positively correlate with the tumor purity of kidney chromophobe, kidney renal clear cell carcinoma, and kidney renal papillary cell carcinoma samples. Besides, the expression of disabled homolog 2-interacting protein in renal cell carcinoma has negative correlation with the immune infiltration, and the immune infiltration of B cells and CD8+ T cells affects the prognosis of kidney renal papillary cell carcinoma. Enrichment analysis of disabled homolog 2-interacting protein co-expressed genes suggested that its biological role was mainly in regulating GTPase activity. Conclusions: These findings suggest that disabled homolog 2-interacting protein functions as a tumor suppressor in the progression of renal cell carcinoma, and the expression of disabled homolog 2-interacting protein is related to the immune infiltrating cells and affects the survival of renal cell carcinoma. Disabled homolog 2-interacting protein can be a novel clinical biomarker for patients with renal cell carcinoma, which also provides new insights for the future treatments of renal cell carcinoma.

Download Full-text

An Integrated Analysis of The Prognosis And Immune Cell Infiltration of ITGB Superfamily Members In Gastric Cancer

10.21203/rs.3.rs-689050/v1 ◽

2021 ◽

Author(s):

Chuan-hong Li ◽

Lei Meng ◽

Zhang-ming Chen ◽

Wan-nian Sui ◽

Pei-feng Chen ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Cell Adhesion ◽

Mrna Expression ◽

Cell Lines ◽

Survival Data ◽

Expression Patterns ◽

Expression Level ◽

Integrated Analysis ◽

Expression Levels

Abstract Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.

Download Full-text

MicroRNA-625 inhibits cell invasion and epithelial–mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20181882 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 4

Author(s):

Yuan Li ◽

Chenjuan Tao ◽

Lili Dai ◽

Caixia Cui ◽

Chaohui Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Critical Role ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Expression Levels

AbstractIntroduction: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC.Materials and methods: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3′-UTR of SOX4.Results: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells.Conclusions: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

Download Full-text

Mammalian SIRT4 is a tumor suppressor of clear cell renal cell carcinoma by inhibiting cancer proliferation, migration and invasion

Cancer Biomarkers ◽

10.3233/cbm-191253 ◽

2020 ◽

Vol 29 (4) ◽

pp. 453-462 ◽

Cited By ~ 2

Author(s):

Changming Wang ◽

Chiyuan Piao ◽

Junlong Liu ◽

Zhe Zhang ◽

Yuyan Zhu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Tumor Suppressor ◽

Cell Carcinoma ◽

Survival Data ◽

Renal Cell ◽

Clear Cell ◽

Expression Level ◽

Migration And Invasion ◽

Advanced Tumor Stage ◽

Cell Renal Cell Carcinoma

OBJECTIVE: Sirtuins family are defined as class III histone deacetylases (HDACs). Recently, mammalian silent information regulator two 4 (SIRT4) has been reported to be a tumor suppressor gene in multiple cancers. The objective of the present study was to explore the potential role of SIRT4 in clear cell renal cell carcinoma (ccRCC). METHODS: We estimated SIRT4 expression levels in ccRCC and its adjacent non-neoplastic tissue by Western blotting (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and bioinformatics data, the clinical and survival data were also collected and analyzed. In vitro study, ccRCC cell lines were transfected with SIRT4-siRNA or lentivirus to downregulate or overexpress the expression level of SIRT4. Then, the proliferation capacity of tumor cell was assessed by 5-Ethynyl-2’-deoxyuridine (EDU) assay, cell migration and invasion capacity were assessed by Transwell assays. RESULTS: Our results indicated that the expression level of SIRT4 in ccRCC was significantly lower than the corresponding normal tissues (P< 0.001). Meanwhile, bioinformatics data and the result of WB showed that low SIRT4 expression level was obviously involved with poor overall survival and advanced tumor stage in ccRCC patients. Biological experiments demonstrated that overexpression of SIRT4 significantly reduced the proliferation, migration and invasion ability of ccRCC cells. Conversely, downregulation of SIRT4 enhanced the proliferation, migration and invasion ability of ccRCC cells. CONCLUSIONS: These findings support that SIRT4 acts as a tumor suppressor in ccRCC and might be a novel biomarker and new therapeutic target for ccRCC.

Download Full-text

ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors

10.21203/rs.3.rs-58757/v3 ◽

2021 ◽

Author(s):

Hai Zhu ◽

Gang Wang ◽

Haixing Zhu ◽

Aman Xu

Keyword(s):

Gastric Cancer ◽

Western Blot ◽

Prognostic Biomarker ◽

Functional Enrichment ◽

Expression Level ◽

Gastrointestinal Tumors ◽

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 tumors remain unclear.Methods: The expression level of ITGA5 was 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, immunohistochemistry (IHC) staining and western blot 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 gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal 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 and western blot 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 was 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 gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.

Download Full-text

RNF208 is a Biomarker Associated with Immune Infiltration in Low-Grade Gliomas

10.21203/rs.3.rs-836757/v1 ◽

2021 ◽

Author(s):

tong cheng ◽

Manyu Xu ◽

Bowen Wu ◽

Sutian Jiang ◽

Qianqian Wu ◽

...

Keyword(s):

Cox Regression ◽

Univariate Analysis ◽

Gene Set Enrichment Analysis ◽

Expression Level ◽

Low Grade ◽

Who Grade ◽

Expression Levels ◽

Immune Infiltration ◽

Low Grade Gliomas ◽

Infiltrating Cells

Abstract Background: Gliomas that contain common tumors originating in the central nervous system include low-grade gliomas (LGGs) and high-grade gliomas (HGGs). RNF208 is a gene that has not been researched in LGGs. Methods: Our study appraised the function of RNF208 in LGGs using data from The Cancer Genome Atlas (TCGA) database. The RNF208 expression level was analyzed via the Oncomine and TCGA database. The association between RNF208 expression levels and the clinical survival outcomes was evaluated by using COX regression and Kaplan-Meier plotting analysis. CIBERSORT was applied to investigate the correlation between RNF208 expression levels and cancer immune infiltrating cells. To explore relevant biological processes, we carried out Gene Set Enrichment Analysis. A protein network interacting with RNF208 was also established using the STRING tool. Results: A group of data of LGGs patients based on the TCGA database revealed that high RNF208 expression level was relevant to a favorable prognosis. Besides, RNF208 expression that served as an independent factor was significantly correlated with WHO grade groups in univariate analysis. Furthermore, RNF208 expression was negatively correlated with the immune infiltration level of 22 species of immune infiltrating cells and immune checkpoints including PD1, PDL2, TIM3, and CTLA4. GSEA showed that 20 biological pathways were discriminatively enriched in the RNF208 low expression level. Conclusions: Our findings revealed that RNF208 would be regarded as a promising prognostic biomarker in LGGs.

Download Full-text

XXYLT1 Methylation Contributes to the Occurrence of Lung Adenocarcinoma

10.21203/rs.2.22275/v1 ◽

2020 ◽

Author(s):

Hui Zeng ◽

ying wang ◽

yongjun zhang

Keyword(s):

Dna Methylation ◽

Lung Adenocarcinoma ◽

Mrna Expression ◽

Methylation Status ◽

Additional Research ◽

Expression Level ◽

Methylation Data ◽

Expression Levels ◽

Male Patients ◽

Cancer Tissues

Abstract Objective: This study aimed to observe the methylation levels and mRNA expression of XXYLT1 and to further analyze their possible correlation with the risk of lung adenocarcinoma. Methods: Thirty patients with lung adenocarcinoma (fifteen men and fifteen women) were recruited in this study. Cancer tissues and para-carcinoma tissues were obtained from each of the patients. The expression levels of XXYLT1 mRNA were determined, and the DNA methylation status was analyzed by MassARRAY Spectrometry. The methylation data of individual units were generated by EpiTyper v1.0.5 software. Results: Among the male patients, the expression level of XXYLT1 mRNA was significantly higher in the para-carcinoma tissues compared to the cancer tissues. Meanwhile, among the male patients, the methylation rates of three CpG units (CpG_23, CpG_25, and CpG_60.61.62.63.64.65) within the XXYLT1 gene were lower in the para-carcinoma tissues compared to the cancer tissues.Conclusions: Our results show that XXYLT1 mRNA was down-regulated and methylation rates were increased in lung adenocarcinoma tissues than in para-carcinoma tissues. These suggested that methylation of XXYLT1 may have significance in the pathogenesis of lung adenocarcinoma. Additional research is required to elucidate this aspect.

Download Full-text

Overexpressing PTTG family genes predict poor prognosis in kidney renal clear cell carcinoma

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02225-2 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yonghui Gui ◽

Xueni Liu ◽

Chao Wang ◽

Peng Yang

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Renal Clear Cell Carcinoma ◽

Expression Level ◽

Pathway Enrichment Analysis ◽

Term Survival ◽

Clinical Indicators

Abstract Background Pituitary tumor transforming genes (PTTG1, PTTG2, and PTTG3P) play key roles in the pathogenesis and development of human cancers. The studies show that overexpression of the PTTG genes is associated with tumor progression and migration. However, the function of the PTTG genes in the prognostic value of kidney renal clear cell carcinoma is rarely known by people. Methods The expression of PTTG family genes was analyzed by the ONCOMINE, Human Protein Atlas, GEPIA2, and UALCAN database. The relationship between PTTG family genes expression level and clinical indicators including prognostic data in kidney renal clear cell carcinoma was analyzed by GEPIA2, TCGA portal, and UALCAN. cBioPortal database was used to analyze the genetic mutations of differentially expressed PTTG family members. Similar genes of the PTTG family (90 in total) obtained from GEPIA2 and Metascape were used for GO enrichment to explore the interaction among similar genes. The online tools of Metascape and STRING were used for functional and pathway enrichment analysis. Results PTTG1, 2, and 3P mRNA and protein expression upregulated in kidney renal clear cell carcinoma kidney renal clear cell carcinoma patients compared with normal tissues. And higher expression level of PTTG family genes was associated with shorter overall survival (OS) and disease-free survival (DFS). Furthermore, overexpression of the PTTG family genes had been found correlated with individual cancer stages and pathological tumor grades. In addition, 18% of mutations in the PTTG family genes were associated with short-term survival in kidney renal clear cell carcinoma patients. Conclusions A single PTTG gene or PTTG family genes as a whole may be a potential prognostic biomarker for kidney renal clear cell carcinoma.

Download Full-text