Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy

Asian Pac J Cancer Prev. 2014;15(10):4153-8. doi: 10.7314/apjcp.2014.15.10.4153.

Abstract

Background: This study was aimed to establish a novel method to simultaneously detect expression of four genes, ribonucleotide reductase subunit M1(RRM1), X-ray repair cross-complementing gene 1 (XRCC1), thymidylate synthase (TS) and class III β-tubulin (TUBB3), and to assess their application in the clinic for prediction of response of non-small cell lung cancer (NSCLC) to chemoradiotherapy.

Materials and methods: We have designed four gene molecular beacon (MB) probes for multiplex quantitative real-time polymerase chain reactions to examine RRM1, XRCC1, TUBB3 and TS mRNA expression in paraffin-embedded specimens from 50 patients with advanced or metastatic carcinomas. Twenty one NSCLC patients receiving cisplatin- based first-line treatment were analyzed.

Results: These molecular beacon probes could specially bind to their target genes in homogeneous solutions. Patients with low RRM1 and XRCC1 mRNA levels were found to have apparently higher response rates to chemoradiotherapy compared with those with high levels of RRM1 and XRCC1 expression (p<0.05). The TS gene expression level was not significantly associated with chemotherapy response (p>0.05).

Conclusions: A method of simultaneously detecting four molecular markers was successfully established and applied for evaluation of chemoradiotherapy response. It may be a useful tool in personalized cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Chemoradiotherapy
  • Chemoradiotherapy, Adjuvant
  • Cisplatin / therapeutic use
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Ribonucleoside Diphosphate Reductase
  • Thymidylate Synthase / biosynthesis*
  • Thymidylate Synthase / genetics
  • Treatment Outcome
  • Tubulin / biosynthesis*
  • Tubulin / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • TUBB3 protein, human
  • Tubulin
  • Tumor Suppressor Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Deoxycytidine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Thymidylate Synthase
  • Cisplatin
  • Gemcitabine