Dataset Information

SPINK5 is a Prognostic Biomarker Associated With the Progression and Prognosis of Laryngeal Squamous Cell Carcinoma Identified by Weighted Gene Co-Expression Network Analysis.

ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) is one of the most common types of head and neck squamous cell carcinomas (HNSCC) and is the second most prevalent malignancy occurring in the head and neck or respiratory tract, with a high incidence and mortality rate. Survival is limited for patients with LSCC. To identify more biomarkers associated with the prognosis of patients with LSCC, using bioinformatics analysis, this study used The Cancer Genome Atlas (TCGA) LSCC dataset and gene expression profiles of GSE59102 from the Gene Expression Omnibus (GEO). Eighty-one differentially co-expressed genes were identified by weighted gene co-expression network analysis (WGCNA). Next, 10 hub genes (PPL, KRT78, CRNN, PTK7, SCEL, AGRN, SPINK5, AIF1L, EMP1, and PPP1R3C) were screened from a protein-protein interaction (PPI) network. Based on survival analysis, SPINK5 was significantly correlated with survival time in LSCC patients. After verification in the TCGA and HPA databases, SPINK5 was selected as a prognostic biomarker. Finally, the GSEA results showed that downregulation of SPINK5 gene expression may promote tumorigenesis and the development of cancers by the "BASAL CELL CARCINOMA" pathway, and it has been implicated in disrupting DNA damage and repair pathways. Collectively, SPINK5 may serve as a potential prognostic biomarker in LSCC.

SUBMITTER: Liu J

PROVIDER: S-EPMC8819746 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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SPINK5 is a Prognostic Biomarker Associated With the Progression and Prognosis of Laryngeal Squamous Cell Carcinoma Identified by Weighted Gene Co-Expression Network Analysis.

Liu Jian J Zhao Jing J Xu Jiaran J Sun Qing Q Qin Xuemei X Chen Guohui G Gao Tianle T Bai Guangping G Guo Zhiqiang Z

Evolutionary bioinformatics online 20220204

Laryngeal squamous cell carcinoma (LSCC) is one of the most common types of head and neck squamous cell carcinomas (HNSCC) and is the second most prevalent malignancy occurring in the head and neck or respiratory tract, with a high incidence and mortality rate. Survival is limited for patients with LSCC. To identify more biomarkers associated with the prognosis of patients with LSCC, using bioinformatics analysis, this study used The Cancer Genome Atlas (TCGA) LSCC dataset and gene expression pr ...[more]

PMID: 35140453

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Project description:Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck, and can seriously affect the daily life of patients. To study the mechanisms of LSCC, the microarray of GSE51958 was analyzed in the present study. GSE51958 was downloaded from Gene Expression Omnibus, and included a collection of LSCC tissue samples and matched adjacent non-cancerous tissue samples from 10 patients. Differentially-expressed genes (DEGs) were identified using limma package. Next, a weighted co-expression network was constructed for the DEGs by WGCNA package in R. Modules of the weighted co-expression network were obtained through constructing a hierarchical clustering tree using the hybrid dynamic shear tree method. Using the clusterProfiler package, the potential functions of DEGs in the modules correlated with LSCC were predicted by pathway enrichment analysis. In total, 959 DEGs were screened from the LSCC samples compared with the adjacent non-cancerous samples, including 553 upregulated and 406 downregulated genes. The appointed black, brown, gray, pink and yellow modules were screened for the DEGs in the weighted co-expression network. For the DEGs in the brown and yellow modules, the enriched pathways were cytokine-cytokine receptor interaction and metabolic pathways, respectively. The DEGs in the pink module were involved in the majority of pathways. With high connectivity degrees in the pink module, TPX2, microtubule-associated (TPX2; degree, 25), minichromosome maintenance complex component 2 (MCM2; degree, 25), ubiquitin-like with PHD and ring finger domains 1 (UHRF1; degree, 22), cyclin-dependent kinase 2 (CDK2; degree, 20) and protein regulator of cytokinesis 1 (PRC1; degree, 20) may be involved in LSCC. Overall, In conclusion, from the integrated bioinformatics analysis of genes that may be associated with LSCC, 959 DEGs were obtained from LSCC samples compared with adjacent non-cancerous samples, and TPX2, MCM2, UHRF1, CDK2 and PRC1 were found to hold a possible association with the disease.

Project description:Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.

Project description:BackgroundThe application of coagulation-related markers in laryngeal squamous cell carcinoma(LSCC) remains unclear. This study explored the prognostic role of coagulation markers in the progression and metastasis of LSCC.MethodsCoagulation markers of patients with LSCC receiving surgery in the Second Affiliated Hospital of Fujian Medical University in China, from January 2013 to May 2022 were retrospectively analyzed and compared with those of contemporary patients with benign laryngeal diseases. The relationship between clinicopathological features of LSCC and coagulation markers was analyzed with the chi-square and rank sum tests. The ROC curve analysis was utilized to evaluate the diagnostic efficacy of seven coagulation markers for LSCC and its different clinicopathological features, and to find the optimal cutoff value of each coagulation marker.Results303 patients with LSCC and 533 patients with benign laryngeal diseases were included in the present analysis. Compared to the control group, prothrombin time (PT) (p < 0.001), activated partial thromboplastin time (APTT) (p = 0.001), and Fib (p < 0.001) in patients with LSCC were significantly higher, while mean platelet volume (MPV) (p < 0.001) was significantly shorter. Significant increases were detected in PT (Z = 14.342, p = 0.002), Fib (Z = 25.985, p < 0.001), platelet count (PC) (Z = 12.768, p = 0.005), PCT (Z = 9.178, p = 0.027), MPV (F = 2.948, p = 0.033) in T4 stage. Fib had the highest prognostic value among the seven coagulation markers in different T stages (AUC = 0.676, p < 0.001), N stages (AUC = 0.717, p < 0.001), tumor stage (AUC = 0.665, p < 0.001), differentiation degree (AUC = 0.579, p = 0.022), and neurovascular invasion (AUC = 0.651, p = 0.007). Fib (Z = 25.832, p < 0.001), PC (Z = 23.842, p < 0.001), and PCT (Z = 20.15, p < 0.001) in N1 and N3 stages were significantly higher than in N0 stage. PT (Z = 12.174, p = 0.007), Fib (Z = 23.873, p < 0.001), PC (Z = 17.785, p < 0.001), and PCT (Z = 14.693, p = 0.002) were significantly higher in stage IV than in stage I and II. APTT (Z=-1.983, p = 0.047), Fib (Z=-2.68, p = 0.007), PC (Z=-2.723, p = 0.006), and PCT (Z=-2.592, p = 0.01) increased significantly when the tumor invaded neurovascular tissue.ConclusionsCoagulation markers have the potential to act as biomarkers for predicting pathological features of LSCC. The high level of Fib was helpful for the diagnosis of LSCC and the detection of advanced LSCC.Trial registrationNot applicable.

Dataset Information

SPINK5 is a Prognostic Biomarker Associated With the Progression and Prognosis of Laryngeal Squamous Cell Carcinoma Identified by Weighted Gene Co-Expression Network Analysis.

Publications

SPINK5 is a Prognostic Biomarker Associated With the Progression and Prognosis of Laryngeal Squamous Cell Carcinoma Identified by Weighted Gene Co-Expression Network Analysis.

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