PBXIP1 – An indicator for poor outcome and metastatic spread in colorectal cancer

Abstract

Tumor cell heterogeneity in colorectal cancers within the same genetic background is a well-described phenomenon. In this work, we investigate the role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in tumor cell subpopulations with differential Wingless-related integration site (WNT) activity as well as its potential associations with epithelial-mesenchymal transition (EMT) and clinical associations in colorectal cancer. We used in situ analyses to identify immunohistochemical expression of PBXIP1 in normal and colorectal cancer tissues and biostatistical approaches to determine its function and regulatory correlations. Clinical associations were analyzed in a case control collection of metastatic and non-metastatic colon cancers and gene expression data sets of colorectal cancers with recorded clinical follow-up data. PBXIP1 was expressed in single epithelial cells from tumor-free colon crypts as well as in tumor cells with high WNT activity. Colorectal cancer cells close to the invasive edge seemed to possess higher PBXIP1 levels indicative of associations with EMT, whereas stromal cells in the tumor microenvironment appeared mostly negative. PBXIP1 expression was associated with local metastasis to lymph nodes as well as distant metastasis to secondary organs in a case-control collection consisting of 91 cases with or without distant metastasis. Furthermore, high expression of PBXIP1 in The Cancer Genome Atlas (TCGA) data set was associated with worse overall survival in colon cancer. PBXIP1 might serve as a novel histological prognostic and regulatory indicator for EMT processes in colorectal cancer that seems to correlate with cancer cell subtypes of high baseline WNT activity.