Stem Cell Marker Expression in Early Stage Colorectal Cancer is Associated with Recurrent Intestinal Neoplasia
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ORIGINAL SCIENTIFIC REPORT
Stem Cell Marker Expression in Early Stage Colorectal Cancer is Associated with Recurrent Intestinal Neoplasia Brett S. Walker1 • Luai R. Zarour1 • Nicole Wieghard1 • Alexandra C. Gallagher2 John R. Swain2 • Sheila Weinmann3 • Christian Lanciault4 • Kevin Billingsley1,5 • V. Liana Tsikitis1,5 • Melissa H. Wong2,5
•
Ó Socie´te´ Internationale de Chirurgie 2020
Abstract Background 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. Methods 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. Results 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 earlystage 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 CD166associated molecules revealed elevated ASCL2 in primary tumors from patients who recurred. Conclusions We identified a protein signature prognostic of aggressive disease in early stage CRC. Stem cellassociated 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.
Brett S. Walker and Luai R. Zarour contributed equally.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00268-020-05586-z) contains supplementary material, which is available to authorized users. & V. Liana Tsikitis [email protected] & Melissa H. Wong [email protected] 1
Department of Surgery, OHSU, 3181 SW Sam Jackson Park Rd, L619, Portland, OR 97239, USA
2
Department of Cell, Developmental, and Cancer Biology, OHSU, 2720 S Moody Ave., KR-CDCB, Portland, OR 97201, USA
3
Kaiser Permanente Northwest Center for Health Research, 3800 N. Interstate Ave., Portland, OR 97227, USA
4
Department of Pathology, OHSU, 3181 SW Sam Jackson Park Rd, L-113, Portland, OR 97239, USA
5
Knight Cancer Institute, Oregon Health & Science University, 2720 S Moody Ave., Portland, OR 97201, USA
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World J Surg
Introduction Colorectal cancer (CRC) is the second leading cause of canc
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