Low expression of CD24 is associated with poor survival in colorectal cancer
| Autor: | Lena-Christin Conradi, Tobias Lange, Stepan Nersisyan, Hanibal Bohnenberger, Ann-Kristin Ahlers, Alexander G. Tonevitsky, Sandra Genduso, Udo Schumacher, Alexei V. Galatenko, Maria Raygorodskaya, J. A. Makarova, Omar Elakad, Daniel Wicklein, D. V. Maltseva, Hanna Maar, Alina Schiecke |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Colorectal cancer Biochemistry Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Laminin Gene expression medicine Humans skin and connective tissue diseases 030304 developmental biology Aged 0303 health sciences Gene knockdown biology CD24 CD24 Antigen Cell migration General Medicine Middle Aged medicine.disease 3. Good health Neoplasm Proteins Gene Expression Regulation Neoplastic Survival Rate Apoptosis 030220 oncology & carcinogenesis biology.protein Cancer research Immunohistochemistry Female Colorectal Neoplasms HT29 Cells |
| Zdroj: | Biochimie. 192 |
| ISSN: | 1638-6183 |
| Popis: | In this study we analyzed expression of CD24 in a cohort of colorectal cancer patients using immunohistochemistry staining of CD24. We found a significant association between absence or low expression of CD24 (10% of membranous and 55% of cytoplasmic staining) and shortened patient survival. Protein localization played a crucial role in the prognosis: membranous form was the major and prognostic one in primary tumors, while cytoplasmic expression was elevated in liver metastases compared to the primary tumors and contained prognostic information. Then, using The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) RNA-seq data, we showed that CD24 mRNA level was two-fold decreased in primary colorectal cancers compared to adjacent normal mucosa. Like the protein staining data, ten percent of patients with the lowest mRNA expression levels of CD24 in primary tumors had reduced survival compared to the ones with higher expression. To explain these findings mechanistically, shRNA-mediated CD24 knockdown was performed in HT-29 colorectal cancer cells. It resulted in the increase of cell migration in vitro, no changes in proliferation and apoptosis, and a slight decrease in cell invasion. As increased cell migration is a hallmark of metastasis formation, this finding corroborates the association of a decreased CD24 expression with poor prognosis. Differential gene expression analysis revealed upregulation of genes involved in cell migration in the group of patients with low CD24 expression, including integrin subunit α3 and α3, β3 subunits of laminin 332. Further co-expression analysis identified SPI1, STAT1 and IRF1 transcription factors as putative master-regulators in this group. |
| Databáze: | OpenAIRE |
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