Stem Cell Marker Expression in Early Stage Colorectal Cancer is Associated with Recurrent Intestinal Neoplasia
| Autor: | Christian Lanciault, Sheila Weinmann, Brett S. Walker, Nicole Wieghard, Melissa H. Wong, Alexandra C. Gallagher, V. Liana Tsikitis, Kevin G. Billingsley, John R. Swain, Luai Zarour |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Adult Fetal Proteins Male medicine.medical_specialty Colorectal cancer Cell Adhesion Molecules Neuronal Stem cell marker Receptors G-Protein-Coupled 03 medical and health sciences 0302 clinical medicine Antigens CD Internal medicine medicine Adjuvant therapy Biomarkers Tumor Humans Neoplasm Staging biology business.industry CD44 LGR5 Cancer Middle Aged medicine.disease Hyaluronan Receptors BMI1 030220 oncology & carcinogenesis biology.protein Neoplastic Stem Cells 030211 gastroenterology & hepatology Surgery Female Stem cell Neoplasm Recurrence Local business Colorectal Neoplasms |
| Zdroj: | World journal of surgery. 44(10) |
| ISSN: | 1432-2323 |
| Popis: | Colorectal cancer (CRC) ranks second in cancer deaths worldwide and presents multiple management challenges, one of which is identifying high risk stage II disease that may benefit from adjuvant therapy. Molecular biomarkers, such as ones that identify stem cell activity, could better stratify high-risk cohorts for additional treatment. To identify possible biomarkers of high-risk disease in early-stage CRC, a discovery set (n = 66) of advanced-stage tumors were immunostained with antibodies to stemness proteins (CD166, CD44, CD26, and LGR5) and then digitally analyzed. Using a second validation cohort (n = 54) of primary CRC tumors, we analyzed protein and gene expression of CD166 across disease stages, and extended our analyses to CD166-associated genes (LGR5, ASCL2, BMI1, POSTN, and VIM) by qRT-PCR. Stage III and metastatic CRC tumors highly expressed stem cell-associated proteins, CD166, CD44, and LGR5. When evaluated across stages, CD166 protein expression was elevated in advanced-stage compared to early-stage tumors. Notably, a small subset of stage I and II cancers harbored elevated CD166 protein expression, which correlated with development of recurrent cancer or adenomatous polyps. Gene expression analyses of CD166-associated molecules revealed elevated ASCL2 in primary tumors from patients who recurred. We identified a protein signature prognostic of aggressive disease in early stage CRC. Stem cell-associated protein and gene expression identified a subset of early-stage tumors associated with cancer recurrence and/or subsequent adenoma formation. Signatures for stemness offer promising fingerprints for stratifying early-stage patients at high risk of recurrence. |
| Databáze: | OpenAIRE |
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