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

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

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 ◽  
Author(s):  
Lan Chuan ◽  
Haoyou Tang ◽  
Sheng Liu ◽  
Lin Ma ◽  
Yifu Hou

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jiahui Liu ◽  
Ling Huang ◽  
Yi Zhu ◽  
Yongyin He ◽  
Weiyun Zhang ◽  
...  

T-complex protein-1 ring complex (TRiC), also known as Chaperonin Containing T-complex protein-1 (CCT), is a multisubunit chaperonin required for the folding of nascent proteins. Mounting evidence suggests that TRiC also contributes to the development and progression of tumors, but there are limited studies on pathogenic functions in hepatocellular carcinoma (HCC). We comprehensively evaluated the expression pattern and biological functions of TRiC subunits using The Cancer Genome Atlas and The Human Protein Atlas. Expression levels of TRiC subunits TCP1, CCT2/3/4/5/6A/7/8 were significantly upregulated in HCC tissues at both transcript and protein levels, which predicted shorter overall survival (OS). Moreover, high mutation rates were found in several CCT subunits, and patients with altered CCT genes exhibited poorer clinical outcomes. Functional enrichment analysis showed that co-regulated genes were preferentially involved in ‘protein folding’ and ‘microtubule-based process’, while genes co-expressed with CCT subunits were primarily involved in ‘ribosome’ and ‘spliceosome’. Knockout of CCT5 in a HCC cell line reduced while overexpression enhanced proliferation rate, cycle transition, migration, and invasion. In conclusion, these findings suggest that subunits of the TRiC may be potential biomarkers for the diagnosis of HCC and play an important role in the occurrence and development of HCC.


MicroRNA ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Dimitrios E. Magouliotis ◽  
Vasiliki S. Tasiopoulou ◽  
Ioannis Baloyiannis ◽  
Ioannis Mamaloudis ◽  
George Tzovaras

Background: Rectal Cancer (RC) is a common type of cancer with poor prognosis. The identification of biomarkers regarding RC diagnosis, monitoring, and prognosis is crucial. Objectives: The purpose of the present study was to evaluate the differential expression of the Aquaporin (AQP) gene family network in RC, and the effect of Radiotherapy (RT) on their expression profile, to indicate novel biomarkers and prognostic factors. Methods: We used data mining techniques to construct the network of the AQP-associated genes to determine the Differentially Expressed Genes (DEGs) in RC and in irradiated as compared to nonirradiated RC patients. Furthermore, survival data of The Cancer Genome Atlas (TCGA) were analysed to assess the prognostic role of the DEGs, along with the functional enrichment of gene ontologies and miRNAs related to the DEGs in RC. Results: Microarray data of one PubMed GEO dataset was extracted, incorporating 22 RC and 20 normal rectal tissue samples. Eight DEGs were reported. Four DEGs were up-regulated and four downregulated in RC. Correlations were identified among the DEGs. Deming regression analysis was performed in order to demonstrate the equations describing these correlations. One gene (Aquaporin 3) was downregulated in irradiated RC samples compared with non-irradiated samples. The most significantly affected biological pathways and miRNAs were identified by functional enrichment analysis. Conclusion: The present study demonstrates an eight-gene molecular panel that could facilitate as biomarkers regarding RC patients, which are potential targets of five miRNA families. Finally, our results highlight the effect of radiotherapy on AQPs and the associated pathways in RC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xingxing Zhao ◽  
Hongmei Yao ◽  
Xinyi Li

Alzheimer’s disease (AD) is a neurodegenerative disease with unelucidated molecular pathogenesis. Herein, we aimed to identify potential hub genes governing the pathogenesis of AD. The AD datasets of GSE118553 and GSE131617 were collected from the NCBI GEO database. The weighted gene coexpression network analysis (WGCNA), differential gene expression analysis, and functional enrichment analysis were performed to reveal the hub genes and verify their role in AD. Hub genes were validated by machine learning algorithms. We identified modules and their corresponding hub genes from the temporal cortex (TC), frontal cortex (FC), entorhinal cortex (EC), and cerebellum (CE). We obtained 33, 42, 42, and 41 hub genes in modules associated with AD in TC, FC, EC, and CE tissues, respectively. Significant differences were recorded in the expression levels of hub genes between AD and the control group in the TC and EC tissues (P < 0.05). The differences in the expressions of FCGRT, SLC1A3, PTN, PTPRZ1, and PON2 in the FC and CE tissues among the AD and control groups were significant (P < 0.05). The expression levels of PLXNB1, GRAMD3, and GJA1 were statistically significant between the Braak NFT stages of AD. Overall, our study uncovered genes that may be involved in AD pathogenesis and revealed their potential for the development of AD biomarkers and appropriate AD therapeutics targets.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8261 ◽  
Author(s):  
Guang Wu ◽  
Fei Wang ◽  
Kai Li ◽  
Shugen Li ◽  
Chunchun Zhao ◽  
...  

Background The tumor protein p53 (TP53) mutant is one of the most frequent mutant genes in bladder cancer. In this study, we assessed the importance of the TP53 mutation in bladder cancer progression and drug selection, and identified potential pathways and core genes associated with the underlying mechanisms. Methods Gene expression data used in this study were downloaded from The Cancer Genome Atlas and cBioportal databases. Drug sensitivity data were obtained from the Genomics of Drug Sensitivity in Cancer. We did functional enrichment analysis by gene set enrichment analysis (GSEA) and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We found the TP53 mutation in 50% of bladder cancer patients. Patients with the TP53 mutation were associated with a lower TP53 mRNA expression level, more advanced tumor stage and higher histologic grade. Three drugs, mitomycin-C, doxorubicin and gemcitabine, were especially more sensitive to bladder cancer with the TP53 mutation. As for the mechanisms, we identified 863 differentially expressed genes (DEGs). Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, chemical carcinogenesis and cancer related pathways. The protein–protein interaction network identified the top 10 hub genes. Our results have suggested the significance of TP53 mutation in disease progression and drug selection in bladder cancer, and identified multiple genes and pathways related in such program, offering novel basis for bladder cancer individualized treatment.


Epigenomics ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1175-1191
Author(s):  
Xi Li ◽  
Sihui Yu ◽  
Rui Yang ◽  
Qi Wang ◽  
Xiangnan Liu ◽  
...  

Aim: To uncover a novel lncRNA–miRNA–mRNA network associated with high-grade serous ovarian cancer metastasis. Material & methods: The candidate differentially expressed lncRNAs were obtained from RNA-sequencing data and determined by functional experiments. The downstream miRNAs and mRNAs were identified by bioinformatic prediction and subjected to functional enrichment analysis. Results: The expression levels of lncRNA ENTPD1-AS1/PRANCR/NR2F2-AS1 were reduced in omental metastatic tissues. Similar differential expression patterns of these lncRNAs were also found in lnCAR database and we verified their tumor suppressive roles by performing functional experiments. Furthermore, we predicted miRNAs and mRNAs via bioinformatic tools and validated their alteration in expression levels in presence of lncRNA interference. Conclusion: We proposed a potential ceRNA regulatory mechanism in high-grade serous ovarian cancer omental metastasis


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1144
Author(s):  
Huy-Hoang Dang ◽  
Hoang Dang Khoa Ta ◽  
Truc T. T. Nguyen ◽  
Gangga Anuraga ◽  
Chih-Yang Wang ◽  
...  

G-protein signaling modulators (GPSMs) are a class of proteins involved in the regulation of G protein-coupled receptors, the most abundant family of cell-surface receptors that are crucial in the development of various tumors, including breast cancer. This study aims to identify the potential therapeutic and prognostic roles of GPSMs in breast cancer. Oncomine and UALCAN databases were queried to determine GPSM expression levels in breast cancer tissues compared to normal samples. Survival analysis was conducted to reveal the prognostic significance of GPSMs in individuals with breast cancer. Functional enrichment analysis was performed using cBioPortal and MetaCore platforms. Finally, the association between GPSMs and immune infiltration cells in breast cancer was identified using the TIMER server. The experimental results then showed that all GPSM family members were significantly differentially expressed in breast cancer according to Oncomine and UALCAN data. Their expression levels were also associated with advanced tumor stages, and GPSM2 was found to be related to worse distant metastasis-free survival in patients with breast cancer. Functional enrichment analysis indicated that GPSMs were largely involved in cell division and cell cycle pathways. Finally, GPSM3 expression was correlated with the infiltration of several immune cells. Members of the GPSM class were differentially expressed in breast cancer. In conclusion, expression of GPSM2 was linked with worse distant metastasis-free outcomes, and hence could potentially serve as a prognostic biomarker. Furthermore, GPSM3 has potential to be a possible target for immunotherapy for breast cancer.


2020 ◽  
Author(s):  
Mohsen Ahmadi ◽  
Pegah Mousavi ◽  
Negin Saffarzadeh ◽  
Fatemeh Hajiesmaeili ◽  
Leila Habibipour

AbstractHypoxanthine phosphoribosyl transferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 and Head and Neck Squamous Cell Carcinomas (HNSCC) has not been investigated so far. We first evaluated the expression of HPRT1 at transcriptomic and proteomic levels in tumor and healthy control tissues and its clinical value using The Cancer Genome Atlas (TCGA), Human Protein Atlas, Kaplan-Meier Plotter databases, GSE107591, and quantitative real-time PCR analysis. Then, we employed the COSMIC and cBioPortal databases to assess the mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. Finally, we performed the functional enrichment analysis for HPRT1 co-expressed genes in HNSCC utilizing the Enrichr database. The mRNA and protein expressions of HPRT1 were significantly elevated in HNSCC compared with normal tissues. Besides, the upregulation of HPRT1 expression was correlated with age, sex, pathological stage, and histological grades of HNSCC patients. Moreover, the increased expression of HPRT1 in cancer tissues exhibited a strong capacity for being a promising biomarker for the diagnosis and prognosis of patients with HNSCC. The co-expressed genes of HPRT1 were mainly enriched in several cancer-related processes such as DNA replication and cell cycle. The present study demonstrated that the overexpression of HPRT1 is significantly correlated with the progression of HNSCC and may serve as a useful biomarker for the early detection and risk stratification of patients with HNSCC.


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.


2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.


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