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Article

Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer

1
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
2
Health Management Center, National Taiwan University Hospital, Taipei 100, Taiwan
3
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
4
Centers of Genomic and Precision Medicine, National Taiwan University, Taipei 100, Taiwan
5
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
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Department of Pathology and Forensic Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
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Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
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Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
9
Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei 100, Taiwan
10
Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
*
Author to whom correspondence should be addressed.
Co-senior authors.
Cancers 2020, 12(6), 1527; https://doi.org/10.3390/cancers12061527
Received: 5 May 2020 / Revised: 29 May 2020 / Accepted: 6 June 2020 / Published: 10 June 2020
(This article belongs to the Section Cancer Biomarkers)
Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness. We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them. We examined 20 depressed and 13 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 colorectal cancers (CRCs) to clarify the clinical outcome of depressed neoplasms. CNAs in MYC, CCNA1, and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with a D-marker panel have significantly shorter progression-free survival compared with those without (p = 0.012), especially in stage I (p = 0.049), stages T1+2 (p = 0.027), and proximal cancers (p = 0.002). The positivity of the D-marker panel was an independent risk factor of cancer progression (hazard ratio (95% confidence interval) = 1.52 (1.09–2.11)). Furthermore, the proximal CRCs with D-marker panels had worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those that did not. The D-marker panel may help to optimize treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future. View Full-Text
Keywords: colorectal cancer; CNAs; chemotherapy; MYC; CCNA1; BIRC7 colorectal cancer; CNAs; chemotherapy; MYC; CCNA1; BIRC7
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MDPI and ACS Style

Chang, L.-C.; Chiu, H.-M.; Ho, B.-C.; Chen, M.-H.; Hsu, Y.-C.; Chiu, W.-T.; Su, K.-Y.; Shun, C.-T.; Liang, J.-T.; Yu, S.-L.; Wu, M.-S. Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer. Cancers 2020, 12, 1527. https://doi.org/10.3390/cancers12061527

AMA Style

Chang L-C, Chiu H-M, Ho B-C, Chen M-H, Hsu Y-C, Chiu W-T, Su K-Y, Shun C-T, Liang J-T, Yu S-L, Wu M-S. Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer. Cancers. 2020; 12(6):1527. https://doi.org/10.3390/cancers12061527

Chicago/Turabian Style

Chang, Li-Chun, Han-Mo Chiu, Bing-Ching Ho, Min-Hsuan Chen, Yin-Chen Hsu, Wei-Tzu Chiu, Kang-Yi Su, Chia-Tung Shun, Jin-Tung Liang, Sung-Liang Yu, and Ming-Shiang Wu. 2020. "Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer" Cancers 12, no. 6: 1527. https://doi.org/10.3390/cancers12061527

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