Dataset Information

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and lacks specific diagnostic markers. In this study, we utilized 10 public datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) database to identify a set of significantly differentially expressed genes (DEGs) between tumor and control samples and WGCNA (Weighted Gene Co-Expression Network Analysis) to construct gene co-expression networks incorporating the DEGs from The Cancer Genome Atlas (TCGA) and then identify genes shared between the GEO datasets and key modules. Then, these genes were screened via MCC to identify 20 hub genes. We utilized regression analyses to develop a prognostic model and utilized the random forest method to validate. All hub genes had good diagnostic value for CRC, but only CLCA1 was related to prognosis. Thus, we explored the potential biological value of CLCA1. The results of gene set enrichment analysis (GSEA) and immune infiltration analysis showed that CLCA1 was closely related to tumor metabolism and immune invasion of CRC. These analysis results revealed that CLCA1 may be a candidate diagnostic and prognostic biomarker for CRC.

SUBMITTER: Wei FZ

PROVIDER: S-EPMC7673386 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

Wei Fang-Ze FZ Mei Shi-Wen SW Wang Zhi-Jie ZJ Chen Jia-Nan JN Shen Hai-Yu HY Zhao Fu-Qiang FQ Li Juan J Liu Zheng Z Liu Qian Q

Frontiers in oncology 20201028

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and lacks specific diagnostic markers. In this study, we utilized 10 public datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) database to identify a set of significantly differentially expressed genes (DEGs) between tumor and control samples and WGCNA (Weighted Gene Co-Expression Network Analysis) to construct gene co-expression networks incorporating the DEGs from The Cancer Genome Atlas (TCGA) and then identify ...[more]

PMID: 33251137

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Project description:BackgroundColorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC.AimTo investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC.MethodsData from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions.ResultsBased on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05).ConclusionAPOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.

Project description:Background: Colorectal cancer (CRC) is one of the most common malignant tumors and has high morbidity and mortality rates. Previous studies have shown that TSPEAR mutations are involved in the development and progression of gastric cancer and liver cancer. However, the role of TSPEAR in CRC is still unclear. Methods: In The Cancer Genome Atlas (TCGA) database, 590 CRC patients with complete survival information were analyzed. We assessed TSPEAR expression in a pan-cancer dataset from the TCGA database. Cox regression analysis was performed to evaluate factors associated with prognosis. Enrichment analysis via the R package "clusterProfiler" was used to explore the potential function of TSPEAR. The single-sample GSEA (ssGSEA) method from the R package "GSVA" and the TIMER database were used to investigate the association between the immune infiltration level and TSPEAR expression in CRC. The R package "maftools" was used to explore the association between tumour mutation burden (TMB) and TSPEAR expression in CRC. CCK-8 assays and cell invasion assays were used to detect the effect of TSPEAR and TGIF2 on the biological behavior of CRC cells. Results: Pan-cancer analysis revealed that TSPEAR was upregulated in CRC tissues compared to normal tissues and that high TSPEAR expression was associated with poorer overall survival (OS) (p=0.0053). The expression of TSPEAR increased with increasing TNM stage, T stage, N stage, and M stage. The nomogram constructed with TSPEAR, age, and TNM stage showed better predictive value than TSPEAR, age, or TNM stage alone. Immune cell infiltration analysis revealed that high expression of TSPEAR was associated with lower immune cell infiltration. Tumor mutation burden (TMB) analysis indicated that high expression of TSPEAR was associated with lower TMB (p=0.005), and high TMB was associated with shorter OS (p=0.02). CCK-8 assays and cell invasion assays indicated that in vitro knockdown of TSPEAR inhibited the proliferation, migration, and invasion of CRC cells. In addition, TSPEAR expression may be regulated by the upstream transcription factor TGIF2. Conclusion: TSPEAR expression was higher in CRC tissues than in normal tissues. Its upregulation was significantly associated with a poor prognosis. Additionally, TSPEAR plays a significant role in tumor immunity and the biological behavior of CRC cells. Thus, TSPEAR may become a promising prognostic biomarker and therapeutic target for CRC patients.

Dataset Information

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

Publications

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

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