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Expression of SPARC in colorectal cancer and mechanisms of its effects on cancer cell invasion

SHEN Chao-qin, YAN Ting-ting, CHEN Hao-yan, FANG Jing-yuan, HONG Jie   

  1. Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai 200001, China
  • Online:2016-08-29 Published:2016-08-31
  • Supported by:

    National Natural Science Foundation of China, 31271366, 91129724, 81522008; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, 201268; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support, 20151512

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Abstract:

Objective · To analyze the expression of secreted protein acidic and rich in cysteine (SPARC) in colorectal cancer (CRC) and investigate the role of SPARC in CRC cell invasion and relevant mechanisms. Methods · Bioinformatics data in microarray dataset GSE9348 from Gene Expression Omnibus (GEO) were collected for analyzing the difference in SPARC expression between CRC tissues and normal colorectal tissues. Clinical and prognostic data in microarray dataset GSE12945 from GEO were collected for analyzing the correlation between the expression level of SPARC and the survival time of CRC patients. Univariate Cox survival analysis was used to screen out risk factors influencing the prognosis of CRC patients. Gene set enrichment analysis (GSEA) was performed to gain further insight into the biological pathways involved in CRC progression related to SPARC. Changes in the invasion ability of CRC cell HT29 were observed with Transwell assay after down-regulation of SPARC. Real-time PCR and Western blotting were used to detect the levels of EMT-related genes in HT29 and HCT116 cells after down-regulation of SPARC. Results · The expression of SPARC in CRC tissues was significantly elevated compared with normal colorectal tissues (P = 0.000). The overall survival time was significantly shorter in patients with high expression of SPARC than in patients with low expression of SPARC (P = 0.029). The univariate analysis indicated that lymph node metastasis, distant metastasis, poor histological differentiation, recurrence, and high expression of SPARC were risk factors for the survival time in CRC patients. GSEA analysis showed that genes related to cell migration and wound-healing pathways were enriched in patients with high expression of SPARC. The down-regulation of SPARC in CRC cells could decrease the invasion ability and inhibit the expressions of N-cadherin, TWIST1, and SNAIL2. Conclusion · SPARC is up-regulated in CRC and negatively correlated to the prognosis of patients. SPARC can promote the invasion ability of CRC cells, which may be related to the involvement of SPARC in mesenchymal transition of cells.

Key words: colorectal cancer, secreted protein acidic and rich in cysteine, cell invasion, cell migration, mesenchymal transition