Gene expression profiles of tumor regression grade in locally advanced             rectal cancer after neoadjuvant chemoradiotherapy.
Tumor regression grading (TRG) reportedly has prognostic value in rectal             cancer patients after pre-operative chemoradiotherapy (CRT). The aim of this retrospective             study was to differentiate gene expression profiles based on TRG in residual cancer             cells after CRT. We evaluated pathological response using the criteria of four             TRG systems: the Japanese Society for the Cancer of Colon and Rectum (JSCCR),             Mandard, Dworak and Rödel. Total RNA was obtained using microdissection from 52             locally advanced rectal cancer specimens from patients who underwent pre-operative             CRT to examine the expression levels of 20 genes [PCNA, MKI67, CDKN1A (p21Cip1),             CDK2, CHEK1, PDRG1, LGR5, PROM1 (CD133), CD44, SOX2, POU5F1 (OCT4), LKB1, VEGF,             EGFR, HGF, MET, HIF1, GLUT1, BAX and BCL2] using real-time quantitative RT-PCR.             Gene expression was compared across the four TRG systems. LGR5 gene expression             levels in CRT non-responders were significantly higher than in responders in all             four grading systems. Patients with elevated PDRG1 and GLUT1 gene expression had             poor pathological response in three TRG systems (JSCCR, Dworak and Rödel). MKI67             gene expression in non-responders was significantly higher than in responders             in two grading systems (JSCCR and Rödel). While, BAX gene expression in responders             was significantly higher than in non-responders in the Mandard TRG system. The             results of this study suggest that TRG may reflect characteristics, such as proliferative             activity, stemness potency and resistance to hypoxia, of residual cancer cells             following pre-operative CRT.
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Mie 514-8507, Japan. saigusa@clin.medic.mie-u.ac.jp
Susumu
S
Saigusa
Koji
K
Tanaka
Yuji
Y
Toiyama
Kohei
K
Matsushita
Mikio
M
Kawamura
Yoshinaga
Y
Okugawa
Junichiro
J
Hiro
Yasuhiro
Y
Inoue
Keiichi
K
Uchida
Yasuhiko
Y
Mohri
Masato
M
Kusunoki
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D004268:DNA-Binding Proteins; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; C116884:LGR5 protein, human; C478985:PDRG1 protein, human; D043562:Receptors, G-Protein-Coupled; C495677:SLC2A1 protein, human; D051028:bcl-2-Associated X Protein