Abstract
Genome instability is an essential hallmark in tumor development, including colorectal cancer. We have recently identified the oxysterol binding protein-related protein 3 (ORP3), also known as oxysterol binding protein-like 3 (OSBPL3), as a novel ploidy-control gene, whose knock-out leads to aneuploidy induction and promotes tumor formation, indicating that ORP3 is a bona fide tumor suppressor protein. Here we analyzed expression of ORP3 in a cohort (n = 206) of colon cancer patients in relation to patient survival. We show that low ORP3 mRNA levels correlate with reduced survival of patients with advanced nodal metastasis (N2). While patient survival does not associate with grading when the whole cohort is evaluated, importantly, low ORP3 mRNA levels associate with worse survival of female patients with grade 3 colon cancer. Similarly, low ORP3 mRNA levels associate with worse survival of grade 3 colon cancer patients 70 years of age and younger while low ORP3 mRNA levels seem to be beneficial for colon cancer patients with a T2 tumor size. Together, the data show that ORP3 expression is downregulated during colon cancer progression, which correlates with reduced patient survival. Thus, ORP3 mRNA levels may be a prognostic marker for better stratification of colon cancer patients.
Highlights
Colorectal cancer (CRC) characterized as a multifactorial and heterogeneous disease is the third most common cancer worldwide and the second deadliest in malignancy [1]
We show that low oxysterol binding protein-related protein 3 (ORP3) mRNA levels correlate with reduced survival of colon cancer patients with advanced nodal metastasis (N2)
The study revealed that low ORP3 mRNA levels associate with worse survival of female patients with grade 3 colon cancer
Summary
Colorectal cancer (CRC) characterized as a multifactorial and heterogeneous disease is the third most common cancer worldwide and the second deadliest in malignancy [1]. It has been shown that, MSI-H CRCs represent a heterogeneous group, they exhibit several unique biologic characteristics when compared to microsatellite stable (MSS) colon cancer [14,15,16,17,18] They all share some distinct histologic cancer features with high amounts of tumor-infiltrating lymphocytes [19]. Previous studies revealed ORP’s function as scaffolds for the protein phosphatases, protein phosphatase 2 (PP2A), and haematopoetic protein tyrosine kinase (HePTP), regulating the activity of extracellular signal-regulated kinases (ERK), thereby indicating a role of ORPs in tumor cell signaling [27] Members of this family have been shown to impact cell migration and adhesion. The evaluation of the whole colon cancer cohort (n = 206) indicates that low ORP3 mRNA levels associate with worse survival of patients with advanced nodal metastasis (N2).
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