Down‐regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer

Abstract

To identify novel biomarkers of metastasis of colorectal cancer (CRC), we developed an orthotopic implantation model of murine CRC and selected in vivo M5, a subclone of the SW480 CRC cell line with enhanced potential for metastasis to the liver. We compared the differences in the gene expression profiles between M5 and SW480 cells using gene expression profiling. We found that expression of special AT-rich sequence-binding protein 2 (SATB2) was down-regulated in M5 cells. Immunohistochemical analysis of 146 colorectal tumour samples showed that underexpression of SATB2 was strongly correlated with poor prognosis, tumour invasion, lymph node metastasis, distant metastasis, and Dukes' classification for CRC. Univariate and multivariate survival analyses further showed that SATB2 expression was a potential favourable prognostic factor for CRC. These results demonstrated not only that SATB2 is a potential novel prognostic factor for CRC, but also that selection of a highly metastatic clone of SW480 in vivo coupled with gene expression profiling is a powerful approach to identifying prognostic markers for CRC.

Further delineation of the SATB2 phenotype

“…In colorectal cancer, downregulation of SATB2 is associated with metastasis and poor prognosis. 38,39 Also in laryngeal carcinoma, decreased SATB2 expression is associated with a poorer outcome. 40 In bone and soft tissue tumors, SATB2 has been proposed to be a novel marker for bone osteoblastic differentiation in benign and malignant mesenchymal tumours.…”

The role of nuclear organization in cancer

“…High SATB2 expression is also found in aggressive breast cancer with poor clinical outcome [67]. Conversely, in colorectal cancer patients, low SATB2 expression is linked to tumour invasion and distant metastases and poor prognosis and may also be suitable as an independent prognostic marker [68].…”

Correlation of SATB1 overexpression with the progression of human rectal cancer

“…In addition to discoveries of these physiological roles, SATB1 has recently attracted considerable attention due to its high expression in various types of malignant tumors, such as breast cancer, gastric cancer and laryngeal cancer, which suggest a crucial role in promoting tumor invasion and metastasis [7][8][9][10]. A recent study showed that the expression of SATB2, a closely related homolog of SATB1, is associated with metastasis and poor prognosis in CRC [11]. However, the relationship between SATB1 and CRC has not been reported.…”