Effectiveness of gene expression profiling for response prediction of rectal cancer to preoperative radiotherapy.
BACKGROUND
Our aim was to determine whether the expression levels of specific genes could predict clinical radiosensitivity in human colorectal cancer.


METHODS
Radioresistant colorectal cancer cell lines were established by repeated X-ray exposure (total, 100 Gy), and the gene expressions of the parent and radioresistant cell lines were compared in a microarray analysis. To verify the microarray data, we carried out a reverse transcriptase-polymerase chain reaction analysis of identified genes in clinical samples from 30 irradiated rectal cancer patients.


RESULTS
A comparison of the intensity data for the parent and three radioresistant cell lines revealed 17 upregulated and 142 downregulated genes in all radioresistant cell lines. Next, we focused on two upregulated genes, PTMA (prothymosin alpha) and EIF5a2 (eukaryotic translation initiation factor 5A), in the radioresistant cell lines. In clinical samples, the expression of PTMA was significantly higher in the minor effect group than in the major effect group (P = 0.004), but there were no significant differences in EIF5a2 expression between the two groups.


CONCLUSIONS
We identified radiation-related genes in colorectal cancer and demonstrated that PTMA may play an important role in radiosensitivity. Our findings suggest that PTMA may be a novel marker for predicting the effectiveness of radiotherapy in clinical cases.
Ojima
Eiki
E
Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan.
Inoue
Yasuhiro
Y
Miki
Chikao
C
Mori
Masaki
M
Kusunoki
Masato
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000528:radiation effects; D001706:Biopsy; D003082:Colectomy; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010448:Peptide Initiation Factors / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D011300:Preoperative Care / Q000379:methods*; D011379:Prognosis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000528:radiation effects; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013947:Thymosin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D000097574:Eukaryotic Translation Initiation Factor 5A
D014408:Biomarkers, Tumor; D010448:Peptide Initiation Factors; D011498:Protein Precursors; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D013947:Thymosin; D000097574:Eukaryotic Translation Initiation Factor 5A; C040782:prothymosin alpha