Chang Li-Chun, Chiu Han-Mo, Ho Bing-Ching, Chen Min-Hsuan, Hsu Yin-Chen, Chiu Wei-Tzu, Su Kang-Yi, Shun Chia-Tung, Liang Jin-Tung, Yu Sung-Liang, Wu Ming-Shiang
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
Health Management Center, National Taiwan University Hospital, Taipei 100, Taiwan.
Cancers (Basel). 2020 Jun 10;12(6):1527. doi: 10.3390/cancers12061527.
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 , , and 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 ( = 0.012), especially in stage I ( = 0.049), stages T ( = 0.027), and proximal cancers ( = 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.
凹陷型结直肠肿瘤具有较高的恶性潜能且侵袭性迅速。我们研究了凹陷型肿瘤的基因组图谱,并阐明了由其引发的癌症的生存结果和治疗反应。我们通过全基因组拷贝数分析检查了20个凹陷型肿瘤和13个息肉样肿瘤。随后,我们在一个由37个凹陷型肿瘤和42个息肉样肿瘤组成的独立队列中验证了所鉴定的拷贝数改变(CNAs)。最后,在530例结直肠癌(CRCs)中将这些CNAs作为生物标志物进行检测,以阐明凹陷型肿瘤的临床结果。在 、 和 中的CNAs在凹陷型肿瘤中显著富集,并被指定为D标志物组。与没有D标志物组的CRC相比,有D标志物组的CRC无进展生存期显著更短( = 0.012),尤其是在I期( = 0.049)、T期( = 0.027)和近端癌症( = 0.002)中。D标志物组的阳性是癌症进展的独立危险因素(风险比(95%置信区间) = 1.52(1.09 - 2.11))。此外,接受奥沙利铂化疗时,有D标志物组的近端CRC的总生存期和无进展生存期比没有该组的更差。D标志物组可能有助于优化近端CRC的治疗和监测,并开发一种分子检测方法。然而,目前的结果仍然是初步的,未来有必要在前瞻性试验中进行进一步验证。