van den Berg Inge, Smid Marcel, Coebergh van den Braak Robert R J, van Deurzen Carolien H M, de Weerd Vanja, Foekens John A, IJzermans Jan N M, Martens John W M, Wilting Saskia M
Department of Surgery, Erasmus MC-University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Cancers (Basel). 2021 Apr 15;13(8):1903. doi: 10.3390/cancers13081903.
Circular RNAs (circRNAs) appear important in tumor progression of colon cancer (CC). We identified an extensive catalog of circRNAs in 181 chemonaive stage I/II colon tumors, who underwent curative surgery between 2007 and 2014. We identified circRNAs from RNAseq data, investigated common biology related to circRNA expression, and studied the association between circRNAs and relapse status, tumor stage, consensus molecular subtypes (CMS), tumor localization and microsatellite instability (MSI). We identified 2606 unique circRNAs. 277 circRNAs (derived from 260 genes) were repeatedly occurring in at least 20 patients of which 153 showed a poor or even negative ( < 0.3) correlation with the expression level of their linear gene. The circular junctions for circSATB2, circFGD6, circKMT2C and circPLEKHM3 were validated by Sanger sequencing. Multiple correspondence analysis showed that circRNAs were often co-expressed and that high diversity in circRNAs was associated with favorable disease-free survival (DFS), which was confirmed by Cox regression analysis (Hazard Ratio (HR) 0.60, 95% CI 0.38-0.97, = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circNAB1, and circCEP192 were associated with both MSI and CMS. This study represents a showcase of the potential clinical utility of circRNAs for prognostic stratification in patients with stage I-II colon cancer and demonstrated that high diversity in circRNAs is associated with favorable DFS.
环状RNA（circRNAs）在结肠癌（CC）的肿瘤进展中似乎具有重要作用。我们在2007年至2014年间接受根治性手术的181例初治I/II期结肠肿瘤中鉴定出了大量的circRNAs。我们从RNA测序数据中鉴定出circRNAs，研究了与circRNA表达相关的常见生物学特性，并研究了circRNAs与复发状态、肿瘤分期、共识分子亚型（CMS）、肿瘤定位和微卫星不稳定性（MSI）之间的关联。我们鉴定出了2606种独特的circRNAs。277种circRNAs（源自260个基因）在至少20例患者中反复出现，其中153种与它们的线性基因表达水平呈负相关或弱相关（<0.3）。通过桑格测序验证了circSATB2、circFGD6、circKMT2C和circPLEKHM3的环状连接。多重对应分析表明，circRNAs通常共表达，并且circRNAs的高度多样性与良好的无病生存期（DFS）相关，这一点通过Cox回归分析得到了证实（风险比（HR）为0.60，95%置信区间为0.38 - 0.97，P = 0.036）。就单个circRNAs而言，circMGA的缺失与复发显著相关，而circSATB2、circNAB1和circCEP192与MSI和CMS均相关。本研究展示了circRNAs在I-II期结肠癌患者预后分层中的潜在临床应用价值，并表明circRNAs的高度多样性与良好的DFS相关。
