CD24 Expression Level as a Prognostic Marker of Survival in Colorectal Cancer
Researchers of the International Laboratory of Microphysiological Systems of the Faculty of Biology and Biotechnology (HSE University), in collaboration with the Laboratory of Molecular Physiology of the Faculty of Biology and Biotechnology (HSE University), as well as German colleagues from the Institute of Anatomy and Experimental Morphology (Hamburg) and the Institute of Pathology (Göttingen), found an association between low expression of the CD24 protein in patients with colorectal cancer and a decrease in patient survival rate.
The results of the study are published in the journal Biochimie.
CD24 is a glycoprotein that plays various roles in the adaptive immune response, autoimmune diseases, and human malignancies. This protein can also serve as a prognostic marker for the development of metastases and survival in oncology. However, data from studies of the CD24 protein and its association with the clinical and pathological features of colorectal cancer are contradictory: there are results suggesting an association of low survival with both high and low CD24 expression.
In a new study, researchers analyzed CD24 protein expression among colorectal cancer patients using immunohistochemical staining and found a significant association between no/low CD24 expression (10% membrane and 55% cytoplasmic staining) and reduced patient survival. It is important to note that protein localization played a crucial role in prognosis: the membrane form was the main and prognostically significant in primary tumors, while the cytoplasmic expression of CD24 was increased in liver metastases (compared to primary tumors) and contained prognostic information. Moreover, using sequencing data (The Cancer Genome Atlas Colon Adenocarcinoma), the researchers were also able to show that CD24 mRNA levels were halved in colorectal tumors compared to adjacent healthy mucosa. According to sequencing, as with protein staining, ten percent of patients with the lowest levels of CD24 mRNA expression in primary lesions had a reduced survival (compared to patients with higher levels of expression).
To explain the findings from a mechanistic perspective, the researchers also performed shRNA-mediated knockdown of CD24 in HT-29 colorectal cancer cells. This resulted in an increase in cell migration in vitro and a slight decrease in cell invasion; there were no changes in proliferation and apoptosis. Since increased cell migration is known to be a hallmark of metastasis formation, this result confirms the association of the absence/low expression of the CD24 protein with a poor prognosis. Differential analysis of gene expression showed an upregulation of genes involved in cell migration in a group of patients with low expression of CD24, including the a3 subunit of integrins and the a3, b3 subunits of laminin 332. Further analysis of co-expression revealed the transcription factors SPI1, STAT1 and IRF1 as putative master regulators in this group.