TY - JOUR
T1 - Circular rna in chemonaive lymph node negative colon cancer patients
AU - van den Berg, Inge
AU - Smid, Marcel
AU - Coebergh van den Braak, Robert R.J.
AU - van Deurzen, Carolien H.M.
AU - de Weerd, Vanja
AU - Foekens, John A.
AU - Ijzermans, Jan N.M.
AU - Martens, John W.M.
AU - Wilting, Saskia M.
N1 - Funding Information:
Institutional Review Board Statement: This research was funded by Erasmus MC IRB, grant number MEC-2007-088.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - 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 (R < 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, p = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circ-NAB1, 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.
AB - 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 (R < 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, p = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circ-NAB1, 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.
UR - http://www.scopus.com/inward/record.url?scp=85104103064&partnerID=8YFLogxK
U2 - 10.3390/cancers13081903
DO - 10.3390/cancers13081903
M3 - Article
AN - SCOPUS:85104103064
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 8
M1 - 1903
ER -
