Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma

Ren, Dan; Kim, Ik Yong; Koh, Sang Baek; Chang, Sei Jin; Eom, Minseob; Yi, Sang Yeop; Seong, Sehyun; Kim, Mi Dong; Bronner, Mary P.; Cho, Mee Yon

doi:10.1002/jso.21383

Cited by 11 publications

(9 citation statements)

References 23 publications

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“…2C). Additionally, several colorectal biomarkers, including Kirsten rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF) (17), TS, DPD (18), SMAD family member 4 (SMAD4) (19) and most ColoPrint reference genes (8), including multiple C2 domains, transmembrane 1 (MCTP1), cathepsin C (CTSC) and pyridine nucleotide-disulphide oxidoreductase domain 1 (PYROXD1), were in group B, indicating the reliability and reproducibility of these genes for molecular analyses in colorectal cancer. Of note, however, one ColoPrint-related gene, hydroxy-δ-5-steroid dehydrogenase, 3β- and steroid δ-isomerase 1 (HSD3B1), had a wide expression distribution among the time-points.…”

Section: Resultsmentioning

confidence: 99%

Gene profiling and bioinformatics analyses reveal time course differential gene expression in surgically resected colorectal tissues

et al. 2014

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It has previously been reported that gene profiles in surgically-resected colorectal cancer tissues are altered over time possibly due to the different tissue-acquisition methods and sample extraction timing that were used. However, the changes that occur are still not clearly understood. In the present study, time-dependent changes in gene expression profiling in colorectal surgical specimens were analyzed. Normal and tumor tissues at several time-points (0, 30, 60 and 120 min) were extracted, and RNA quality, microarray experiments, quantitative PCR and bioinformatics clustering were performed. Although RNA integrity was preserved 2 h after resection, inherent increased/decreased gene expression was observed from 30–120 min in approximately 10% of genes. Bioinformatics clustering could not distinguish case-by-case, probably due to gene profiling changes. Irregular changes in gene expression after surgical resection were found, which could be a crucial confounding factor for quantitative analyses.

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Section: Resultsmentioning

confidence: 99%

Gene profiling and bioinformatics analyses reveal time course differential gene expression in surgically resected colorectal tissues

et al. 2014

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“…The Response Evaluation Criteria in Solid Tumors (RECIST) were used to evaluate the patients' response following completion of the six cycles of chemotherapy. 1,2 No patient achieved a complete response (CR); 13 patients achieved partial responses and were included in the experimental group, six patients achieved stable disease, and 11 patients had disease progression (PD) and were included in the control group (see Table 1). …”

Section: Subjectsmentioning

confidence: 99%

Establishment of a Predictive Genetic Model for Estimating Chemotherapy Sensitivity of Colorectal Cancer with Synchronous Liver Metastasis

Pan

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Objective: We examined the whole genome expression profile in advanced colorectal cancer (ACC) patients who had received FOLFOX4 chemotherapy to establish a genetic biomarker model predicting chemotherapy sensitivity. Methods: Eligible ACC patients were divided into two groups, based on postchemotherapy evaluation results: specifically, the sensitive group (experimental group) and the resistant group (control group). The genome expression profiles of colorectal cancer tissues were examined using DNA microarray analysis, and differential gene expression was identified using a significance analysis of the microarray. The probe signal log ratios were used to produce the area-under-the-curve, sensitivity, and specificity for candidate genes. Genes exhibiting differential expression and significant predictive power were used to simulate a genetic model for estimating chemotherapy sensitivity. Results: Totally, 30 ACC patients were eligible for the study, 13 assigned to the experimental group and 17 to the control group. In total, 30 genes showing significant differential expression were identified. Seven candidate genes (NKX2-3, FXYD6, TGFB1I1, ACTG2, ANPEP, HOXB8, and KLK11), which exhibited positive or negative correlations, were incorporated into a genetic model, with an overall accurate predication rate of 93.3%. Conclusions: The predictive model involving the seven genes listed had high accuracy in estimating chemotherapy sensitivity to the FOLFOX4 regimen.

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“…Certain previous studies revealed no association between TS expression and the response to pemetrexed, whereas other studies revealed that low TS expression was associated with a high sensitivity to pemetrexed-based chemotherapy (25–27); a meta-analysis favored the latter in NSCLC (7,18). It has also been reported that IHC more accurately predicts the response rate of pemetrexed compared with RT-qPCR, probably because TS protein, but not TS mRNA, exerts activity on DNA synthesis (28). In the present study, the tumors that were sensitive to pemetrexed on performing the CD-DST analysis revealed a slightly higher IHC score for TS compared with those without the sensitivity (P=0.217).…”

Section: Discussionmentioning

confidence: 99%

Protein and mRNA expression of folic acid-associated enzymes as biomarkers for the cytotoxicity of the thymidylate synthase-targeted drugs, pemetrexed and S-1, in non-small cell lung cancer

Kimura

Imamura

Inoue

et al. 2017

Molecular and Clinical Oncology

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The thymidylate synthase (TS)-targeted drugs, pemetrexed and S-1, exert an important role in advanced non-small cell lung cancer (NSCLC) treatment; folic acid-associated enzymes are expected to behave as biomarkers, although their role has yet to be fully elucidated. In the present study, a single-institutional prospective analysis, in which the mRNA and protein expression levels of five folic acid-associated enzymes were evaluated with surgical specimens of NSCLC, was performed. Drug sensitivity was evaluated using a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) in vitro. A total of 50 patients with NSCLC were enrolled, and the mRNA and protein expression levels of five enzymes were assessed in 47 and 46 patients, respectively. A significant association was identified between mRNA and protein expression in TS (r=0.6266), but the correlation between mRNA and protein expression levels for the other four enzymes was poor. TS mRNA expression was significantly higher in poorly differentiated tumors compared with moderately differentiated tumors (P=0.0399). TS protein expression was significantly higher in patients with pleural invasion or lymphatic invasion compared with those lacking them (P=0.027 and 0.030, respectively). CD-DST revealed that none of the tumors that were sensitive to pemetrexed, but not to S-1, were well differentiated, whereas none of the tumors that were sensitive to S-1, but not to pemetrexed, were poorly differentiated. More prominent vascular invasion was observed in the tumors that were sensitive to S-1. The only factors that exhibited the potential to discriminate the cytotoxicity of pemetrexed from S-1 were tumor differentiation grade and vascular invasion.

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Comparative analysis of thymidylate synthase at the protein, mRNA, and DNA levels as prognostic markers in colorectal adenocarcinoma

Abstract: TS genotyping on paraffin-embedded fixed tissues proved to be the most useful method for prediction of outcome of 5-FU treatment in patients with colorectal adenocarcinoma.

Cited by 11 publications

References 23 publications

Gene profiling and bioinformatics analyses reveal time course differential gene expression in surgically resected colorectal tissues

Gene profiling and bioinformatics analyses reveal time course differential gene expression in surgically resected colorectal tissues

Establishment of a Predictive Genetic Model for Estimating Chemotherapy Sensitivity of Colorectal Cancer with Synchronous Liver Metastasis

Protein and mRNA expression of folic acid-associated enzymes as biomarkers for the cytotoxicity of the thymidylate synthase-targeted drugs, pemetrexed and S-1, in non-small cell lung cancer

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