Di-san junyi daxue xuebao (Mar 2022)
Expression and clinical significance of extracellular matrix protein 1 in colorectal cancer
Abstract
Objective To investigate the expression level and clinical significance of extracellular matrix protein 1 (ECM1) in colorectal cancer. Methods The data from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used to compare the difference of ECM1 expression level in colorectal cancer tissues and adjacent tissues, and to explore the relationship of the level with tumor stage and prognosis. Paraffin preserved specimens and fresh specimens preserved at -80 ℃ and their corresponding clinical data were collected from Jiangjin District Central Hospital. The expression of ECM1 in these tissues was detected by immunohistochemical assay, RT-qPCR and Western blotting. Chi-square test was used to analyze the correlation of ECM1 level with patients' clinicopathological features. Kaplan-Meier survival analysis was adopted to analyze the relationship between the expression and prognosis. Cox proportional hazard regression analysis was employed to explore the indicators affecting the prognosis of the patients. ECM1 gene in colorectal cancer in TCGA database was enriched and analyzed by GSEA software to speculate the possible regulatory pathway of the gene involved in the occurrence and development of the cancer. Results Analysis on the data from TCGA database showed that ECM1 expression was higher in colorectal cancer tissues than adjacent normal tissues (P < 0.000 1), and also higher in TNM stage Ⅲ~Ⅳ when compared with stage Ⅰ~Ⅱ colorectal cancer patients (P < 0.05). Survival analysis on the data from GEO database found that the patients with high ECM1 expression had poorer prognosis (P < 0.01). The Results of immunohistochemical, qPCR and Western blotting confirmed that the expression of ECM1 was up-regulated in the cancer tissues than the adjacent normal tissues, and its expression was closely associated with lymph node metastasis (P < 0.01), TNM stage (P < 0.01), nerve invasion (P < 0.05) and serum carcinoembryonic antigen (CEA) level (P < 0.01). Kaplan Meier survival analysis suggested that the overall survival of the patients with high ECM1 expression was significantly shortened (P < 0.01). Cox regression analysis indicated that ECM1 was an independent risk factor for the prognosis (HR=3.556, P < 0.01) and should be used for predicting the prognosis of colorectal cancer. High expression of ECM1 was enriched into gene sets related to extracellular matrix receptor interaction, focal adhesion, cell adhesion molecules and so on. Conclusion ECM1 is highly expressed in colorectal cancer and associated with poor prognosis, and may play important role in the invasion and metastasis of the tumor.
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