Clinical Significance of a Gene Signature Generated from Tumor Budding Grade in Colon Cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-04-23

AUTHORS

Eiji Shinto, Yuichiro Yoshida, Yoshiki Kajiwara, Koichi Okamoto, Satsuki Mochizuki, Masato Yamadera, Takehiro Shiraishi, Ken Nagata, Hitoshi Tsuda, Kazuo Hase, Yoji Kishi, Hideki Ueno

ABSTRACT

BackgroundTumor budding, a microscopic finding of dedifferentiation at the invasive margin, has been reported as a definite prognostic marker in colon cancer (CC). Herein, we aimed to generate a molecular budding signature (MBS) based on DNA microarray data and to examine its prognostic significance.MethodsFrozen tissue samples from 85 patients with stage II/III CC were used for DNA microarray analyses. First, we selected candidate genes that were differentially expressed (twofold change) between the invasive frontal regions and corresponding tumor centers of three extremely high-grade budding tumors. Subsequently, using microarray data from whole-tissue sections of the 85 patients, we selected MBS-constituent genes from the candidates based on correlation to the pathological budding grade. The MBS score was calculated using the sum of the logarithm of the expression of each gene.ResultsWe selected seven MBS-constituent genes: MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, FOXC1. A comparison of relapse-free survival (RFS) rates revealed a significant impact of the MBS score [5-year RFS, 77.4% (score-high) vs. 95.1% (score-low); P = 0.044]. Analyses of public databases revealed that low MBS score patients exhibited better prognosis than those with high-score cancers (GSE14333: 5-year RFS, 83.1% vs. 66.6%, P = 0.028; GSE39582: 5-year disease-free survival, 72.2% vs. 58.1%, P = 0.0005). Multivariate analysis revealed that the MBS score is an independent prognostic indicator in GSE39582 (hazard ratio, 1.611; P = 0.013).ConclusionsWe developed a new gene classification method, i.e., MBS, and demonstrated its clinical relevance as an indicator of high recurrence risk of CC. More... »

PAGES

4044-4054

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-020-08498-3

DOI

http://dx.doi.org/10.1245/s10434-020-08498-3

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https://app.dimensions.ai/details/publication/pub.1126917215

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32328985


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