Thymidylate synthase locus LOH in combination with genotype has prognostic and predictive significance in colorectal cancer

被引:0
作者
Kotake, Masanori [1 ,2 ,3 ,4 ]
Bando, Hiroyuki [2 ]
Kaneko, Mami [1 ,2 ,4 ]
Takemura, Hirofumi [1 ]
Minamoto, Toshinari [4 ]
Kawakami, Kazuyuki [4 ,5 ]
机构
[1] Kanazawa Univ, Grad Sch Med Sci, Dept Gen & Cardiothorac Surg, Kanazawa, Ishikawa 9208641, Japan
[2] Ishikawa Prefectural Cent Hosp, Dept Gastrointestinal Surg, Kanazawa, Ishikawa 9208530, Japan
[3] Kouseiren Takaoka Hosp, Dept Surg, 5-10 Eiraku Cho, Takaoka, Toyama 9338555, Japan
[4] Kanazawa Univ, Canc Res Inst, Div Translat & Clin Oncol, 13-1 Takara Machi, Kanazawa, Ishikawa 9200934, Japan
[5] Tokyo Womens Med Univ, Dept Chemotherapy & Palliat Care, Tokyo 1628666, Japan
关键词
5-fluorouracil; colorectal cancer; genetic polymorphism; loss of heterozygocity; thymidylate synthase; SINGLE NUCLEOTIDE POLYMORPHISM; TANDEM REPEAT SEQUENCE; 18Q ALLELIC LOSS; ADJUVANT CHEMOTHERAPY; ENHANCER REGION; CHROMOSOME; 18Q; STAGE-II; DIHYDROPYRIMIDINE DEHYDROGENASE; FUNCTIONAL-ANALYSIS; PROTEIN EXPRESSION;
D O I
10.3892/mco.2021.2398
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of the current study was to investigate the prognostic and predictive significance of polymorphisms in the thymidylate synthase (TS) gene, alongside the loss of heterozygocity (LOH) at this gene locus in patients with colorectal cancer. Genotyping was carried out for a variable number tandem repeat (VNTR) polymorphism in the TS 5'-untranslated region, a G/C single nucleotide polymorphism (SNP) located within this VNTR, and for TS LOH status in 246 colorectal cancer and paired normal DNA samples. The results were analyzed in relation to clinicopathological features, including the prognostic and predictive significance of TS genotype in patients who underwent curative surgery. Complete VNTR, SNP and LOH information for TS was obtained in 226 cases. No significant associations were observed between normal tissue TS genotype status and clinicopathological features. LOH of TS was observed in 58% of tumor samples and was associated with poor prognosis independently of clinical stage. Cases exhibiting TS LOH were classified into the three groups of 2R/loss, 3G/loss and 3C/loss. Patients with 3C/loss genotype status had poor outcomes when treated by surgery alone, but their survival was similar to patients with other genotypes following Fluorouracil (5-FU)-based adjuvant chemotherapy. The results suggested that LOH of the TS locus may be a significant prognostic factor in colorectal cancer, with the genotype of the residual allele also demonstrating an influence on prognosis. In conclusion, LOH status should be considered when TS genotype is explored as a potential prognostic and predictive marker for 5-FU-based adjuvant chemotherapy in colorectal cancer.
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页数:8
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