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Open Access 01-12-2014 | Research

Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer

Authors: Jie Shen, Jia Wei, Wenxian Guan, Hao Wang, Yitao Ding, Xiaoping Qian, Lixia Yu, Zhengyun Zou, Li Xie, Carlota Costa, Trever Bivona, Rafael Rosell, Baorui Liu

Published in: Journal of Translational Medicine | Issue 1/2014

Abstract

Objective

Personalized chemotherapy based on predictive biomarkers can maximize efficacy. However, tumor tissue obtained at the time of initial diagnosis will not reflect genetic alterations observed at the time of disease progression. We have examined whether plasma mRNA levels can be a surrogate for tumor levels in predicting chemosensitivity.

Methods

In 150 gastric cancer patients, mRNA levels of BRCA1 and TS were assessed in plasma and paired tumor tissue. The Mann-Whitney U-test was used to compare mRNA expression levels between tumor samples exhibiting in vitro sensitivity or resistance to docetaxel and pemetrexed. All statistical tests were two-sided.

Results

There were significant correlations between plasma and tumor mRNA levels of BRCA1 (rho = 0.696, P < 0.001) and TS (rho = 0.620, P < 0.001). BRCA1 levels in plasma (docetaxel-sensitive: 1.25; docetaxel-resistant: 0.50, P < 0.001) and tumor (docetaxel-sensitive: 8.81; docetaxel-resistant: 4.88, P < 0.001) were positively associated with docetaxel sensitivity. TS levels in plasma (pemetrexed-sensitive: 0.90; pemetrexed-resistant: 1.82, P < 0.001) and tumor (pemetrexed-sensitive: 6.56; pemetrexed-resistant: 16.69, P < 0.001) were negatively associated with pemetrexed sensitivity.

Conclusions

Plasma mRNA expression levels mirror those in the tumor and may have a promising role as potential predictive biomarkers for chemotherapy.

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Elimova E, Shiozaki H, Wadhwa R, Sudo K, Chen Q, Estrella JS, Blum MA, Badgwell B, Das P, Song S, Ajani JA: Medical management of gastric cancer: A 2014 update. World J Gastroenterol. 2014, 20 (38): 13637-13647. 10.3748/wjg.v20.i38.13637.PubMedCentralCrossRefPubMed

Lan H, Lin CY, Li Y: Pemetrexed is mildly active with good tolerability in treating patients with gastric cancer. Asian Pac J Cancer Prev. 2014, 15 (17): 7137-7139. 10.7314/APJCP.2014.15.17.7137.CrossRefPubMed

Wei J, Costa C, Ding Y, Zou Z, Yu L, Sanchez JJ, Qian X, Chen H, Gimenez Capitan A, Meng F, Moran T, Benlloch S, Taron M, Rosell R, Liu B: mRNA expression of BRCA1, PIAS1, and PIAS4 and survival after second-line docetaxel in advanced gastric cancer. J Natl Cancer Inst. 2011, 103: 1552-1556. 10.1093/jnci/djr326.CrossRefPubMed

Quinn JE, Kennedy RD, Mullan PB, Gilmore PM, Carty M, Johnston PG, Harkin DP: BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res. 2003, 63: 6221-6228.PubMed

Wang L, Wei J, Qian X, Yin H, Zhao Y, Yu L, Wang T, Liu B: ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel. BMC Cancer. 2008, 8: 97-10.1186/1471-2407-8-97.PubMedCentralCrossRefPubMed

Wei J, Costa C, Shen J, Yu L, Sanchez JJ, Qian X, Sun X, Zou Z, Gimenez-Capitan A, Yue G, Guan W, Rosell R, Liu B: Differential effect of MMSET mRNA levels on survival to first-line FOLFOX and second-line docetaxel in gastric cancer. Br J Cancer. 2014, 110 (11): 2662-2668. 10.1038/bjc.2014.231.PubMedCentralCrossRefPubMed

Hanauske AR, Eismann U, Oberschmidt O, Pospisil H, Hoffmann S, Hanauske-Abel H, Ma D, Chen V, Paoletti P, Niyikiza C: In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression. Invest New Drugs. 2007, 25: 417-423. 10.1007/s10637-007-9060-9.CrossRefPubMed

Chen CY, Chang YL, Shih JY, Lin JW, Chen KY, Yang CH, Yu CJ, Yang PC: Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed. Lung Cancer. 2011, 74: 132-138. 10.1016/j.lungcan.2011.01.024.CrossRefPubMed

Monaco SE, Nikiforova MN, Cieply K, Teot LA, Khalbuss WE, Dacic S: A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases. Hum Pathol. 2010, 41: 94-102. 10.1016/j.humpath.2009.06.019.CrossRefPubMed

10.

Schwarzenbach H, Hoon DS, Pantel K: Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011, 11: 426-437. 10.1038/nrc3066.CrossRefPubMed

11.

Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE: Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases. Clin Cancer Res. 2010, 16: 790-799. 10.1158/1078-0432.CCR-09-2446.CrossRefPubMed

12.

Kalikaki A, Koutsopoulos A, Trypaki M, Souglakos J, Stathopoulos E, Georgoulias V, Mavroudis D, Voutsina A: Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC. Br J Cancer. 2008, 99: 923-929. 10.1038/sj.bjc.6604629.PubMedCentralCrossRefPubMed

13.

Badalian G, Barbai T, Raso E, Derecskei K, Szendroi M, Timar J: Phenotype of bone metastases of non-small cell lung cancer: epidermal growth factor receptor expression and K-RAS mutational status. Pathol Oncol Res. 2007, 13: 99-104. 10.1007/BF02893484.CrossRefPubMed

14.

Salazar F, Molina MA, Sanchez-Ronco M, Moran T, Ramirez JL, Sanchez JM, Stahel R, Garrido P, Cobo M, Isla D, Bertran-Alamillo J, Massuti B, Cardenal F, Manegold C, Lianes P, Trigo JM, Sanchez JJ, Taron M, Rosell R: First-line therapy and methylation status of CHFR in serum influence outcome to chemotherapy versus EGFR tyrosine kinase inhibitors as second-line therapy in stage IV non-small-cell lung cancer patients. Lung Cancer. 2011, 72: 84-91. 10.1016/j.lungcan.2010.07.008.CrossRefPubMed

15.

Nabeya Y, Suzuki T, Furuya A, Koide N, Ohkoshi M, Takiguchi M, Ochiai T, Matsubara H, Hiwasa T: Calpain regulates thymidylate synthase-5-fluoro-dUMP complex levels associated with response to 5-fluorouracil in gastric cancer cells. Cancer Sci. 2011, 102: 1509-1515. 10.1111/j.1349-7006.2011.01978.x.CrossRefPubMed

16.

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J: Paz-Ares, Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012, 13: 239-246. 10.1016/S1470-2045(11)70393-X.CrossRefPubMed

17.

Shen J, Wang H, Wei J, Yu L, Xie L, Qian X, Zou Z, Liu B, Guan W: Thymidylate synthase mRNA levels in plasma and tumor as potential predictive biomarkers for raltitrexed sensitivity in gastric cancer. Int J Cancer. 2012, 131: E938-E945. 10.1002/ijc.27530.CrossRefPubMed

18.

Garcia JM, Garcia V, Pena C, Dominguez G, Silva J, Diaz R, Espinosa P, Citores MJ, Collado M, Bonilla F: Extracellular plasma RNA from colon cancer patients is confined in a vesicle-like structure and is mRNA-enriched. RNA. 2008, 14: 1424-1432. 10.1261/rna.755908.PubMedCentralCrossRefPubMed

19.

Furukawa T, Kubota T, Hoffman RM: Clinical applications of the histoculture drug response assay. Clin Cancer Res. 1995, 1: 305-311.PubMed

20.

Fichtner I, Rolff J, Soong R, Hoffmann J, Hammer S, Sommer A, Becker M, Merk J: Establishment of patient-derived non-small cell lung cancer xenografts as models for the identification of predictive biomarkers. Clin Cancer Res. 2008, 14: 6456-6468. 10.1158/1078-0432.CCR-08-0138.CrossRefPubMed

21.

Hayashi Y, Kuriyama H, Umezu H, Tanaka J, Yoshimasu T, Furukawa T, Tanaka H, Kagamu H, Gejyo F, Yoshizawa H: Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. Intern Med. 2009, 48: 203-208. 10.2169/internalmedicine.48.1659.CrossRefPubMed

22.

Lausen B, Schumacher M: Maximally selected rank statistics. Biometrics. 1992, 48: 73-85. 10.2307/2532740.CrossRef

23.

Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed

24.

Shen Q, Fan J, Yang XR, Tan Y, Zhao W, Xu Y, Wang N, Niu Y, Wu Z, Zhou J, Qiu SJ, Shi YH, Yu B, Tang N, Chu W, Wang M, Wu J, Zhang Z, Yang S, Gu J, Wang H, Qin W: Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol. 2012, 13: 817-826. 10.1016/S1470-2045(12)70233-4.CrossRefPubMed

25.

Tzimagiorgis G, Michailidou EZ, Kritis A, Markopoulos AK, Kouidou S: Recovering circulating extracellular or cell-free RNA from bodily fluids. Cancer Epidemiol. 2011, 35: 580-589. 10.1016/j.canep.2011.02.016.CrossRefPubMed

26.

Terrin L, Rampazzo E, Pucciarelli S, Agostini M, Bertorelle R, Esposito G, DelBianco P, Nitti D, De Rossi A: Relationship between tumor and plasma levels of hTERT mRNA in patients with colorectal cancer: implications for monitoring of neoplastic disease. Clin Cancer Res. 2008, 14: 7444-7451. 10.1158/1078-0432.CCR-08-0478.CrossRefPubMed

27.

Nilsson RJ, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, Widmark A, Gerritsen WR, Verheul HM, Vandertop WP, Noske DP, Skog J, Wurdinger T: Blood platelets contain tumor-derived RNA biomarkers. Blood. 2011, 118: 3680-3683. 10.1182/blood-2011-03-344408.CrossRefPubMed

28.

Garcia V, Garcia JM, Pena C, Silva J, Dominguez G, Lorenzo Y, Diaz R, Espinosa P, de Sola JG, Cantos B, Bonilla F: Free circulating mRNA in plasma from breast cancer patients and clinical outcome. Cancer Lett. 2008, 263: 312-320. 10.1016/j.canlet.2008.01.008.CrossRefPubMed

29.

Wong SC, Lo SF, Cheung MT, Ng KO, Tse CW, Lai BS, Lee KC, Lo YM: Quantification of plasma beta-catenin mRNA in colorectal cancer and adenoma patients. Clin Cancer Res. 2004, 10: 1613-1617. 10.1158/1078-0432.CCR-1168-3.CrossRefPubMed

30.

Perhavec A, Cerkovnik P, Novakovic S, Zgajnar J: The hTERT mRNA in plasma samples of early breast cancer patients, non-cancer patients and healthy individuals. Neoplasma. 2008, 55: 549-554.PubMed

31.

Porika M, Tippani R, Bollam SR, Panuganti SD, Thamidala C, Abbagani S: Serum human telomerase reverse transcriptase: a novel biomarker for breast cancer diagnosis. Int J Clin Oncol. 2011, 16: 617-622. 10.1007/s10147-011-0230-6.CrossRefPubMed

32.

Silva JM, Rodriguez R, Garcia JM, Munoz C, Silva J, Dominguez G, Provencio M, Espana P, Bonilla F: Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells. Gut. 2002, 50: 530-534. 10.1136/gut.50.4.530.PubMedCentralCrossRefPubMed

33.

Silva JM, Dominguez G, Silva J, Garcia JM, Sanchez A, Rodriguez O, Provencio M, Espana P, Bonilla F: Detection of epithelial messenger RNA in the plasma of breast cancer patients is associated with poor prognosis tumor characteristics. Clin Cancer Res. 2001, 7: 2821-2825.PubMed

34.

Tani N, Ichikawa D, Ikoma D, Tomita H, Sai S, Ikoma H, Okamoto K, Ochiai T, Ueda Y, Otsuji E, Yamagishi H, Miura N, Shiota G: Circulating cell-free mRNA in plasma as a tumor marker for patients with primary and recurrent gastric cancer. Anticancer Res. 2007, 27: 1207-1212.PubMed

35.

Xu W, Zhou H, Qian H, Bu X, Chen D, Gu H, Zhu W, Yan Y, Mao F: Combination of circulating CXCR4 and Bmi-1 mRNA in plasma: A potential novel tumor marker for gastric cancer. Mol Med Report. 2009, 2: 765-771. 10.3892/mmr_00000170.CrossRef

36.

Savino M, Parrella P, Copetti M, Barbano R, Murgo R, Fazio VM, Valori VM, Carella M, Garrubba M, Santini SA: Comparison between real-time quantitative PCR detection of HER2 mRNA copy number in peripheral blood and ELISA of serum HER2 protein for determining HER2 status in breast cancer patients. Cell Oncol. 2009, 31: 203-211.PubMedCentralPubMed

Title: Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer
Authors: Jie Shen
Jia Wei
Wenxian Guan
Hao Wang
Yitao Ding
Xiaoping Qian
Lixia Yu
Zhengyun Zou
Li Xie
Carlota Costa
Trever Bivona
Rafael Rosell
Baorui Liu
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-014-0355-2

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Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer

Abstract

Objective

Methods

Results

Conclusions

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