Abstract
Aim:
To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis.
Methods:
Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR.
Results:
Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients.
Conclusion:
Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.
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References
Neville A . Lung cancer. Clin Evid 2005; (14): 1903–20.
Bernal Bernal R, Leon Jimenez A, Jaen Olasolo J, Benitez Rodriguez E, Mateo Vallejo F . Local recurrence after non-small cell lung cancer surgery: prognosis variables. An Med Interna 2008; 25: 55–60.
Ichinose Y, Tsuchiya R, Yasumitsu T, Koike T, Yamato Y, Nakagawa K, et al. Prognosis of non-small cell lung cancer patients with positive pleural lavage cytology after a thoracotomy: results of the survey conducted by the Japan Clinical Oncology Group. Lung Cancer 2001; 31: 37–41.
Okada A, Hirono T, Watanabe T . Safety and prognosis of limited surgery for octogenarians with non-small-cell lung cancer. Gen Thorac Cardiovasc Surg 2012; 60: 97–103.
Pathak AK, Bhutani M, Mohan A, Guleria R, Bal S, Kochupillai V . Non small cell lung cancer (NSCLC): current status and future prospects. Indian J Chest Dis Allied Sci 2004; 46: 191–203.
Okamoto H, Watanabe K . Medical treatment for stage III non-small-cell lung cancer (NSCLC). Gan To Kagaku Ryoho 2007; 34: 841–8.
Brockmoller J, Junker K, Multhoff G . New perspectives in the management of non-small-cell lung carcinoma (NSCLC). Onkologie 2006; 29: 25–8.
Chang A . Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer 2011; 71: 3–10.
Huppi K, Volfovsky N, Mackiewicz M, Runfola T, Jones TL, Martin SE, et al. MicroRNAs and genomic instability. Semin Cancer Biol 2007; 17: 65–73.
Leung AK, Sharp PA . Function and localization of microRNAs in mammalian cells. Cold Spring Harb Symp Quant Biol 2006; 71: 29–38.
Bagnyukova TV, Pogribny IP, Chekhun VF . MicroRNAs in normal and cancer cells: a new class of gene expression regulators. Exp Oncol 2006; 28: 263–9.
Osada H, Takahashi T . MicroRNAs in biological processes and carcinogenesis. Carcinogenesis 2007; 28: 2–12.
Pfeffer S, Voinnet O . Viruses, microRNAs and cancer. Oncogene 2006; 25: 6211–9.
Cortez MA, Welsh JW, Calin GA . Circulating microRNAs as noninvasive biomarkers in breast cancer. Recent Results Cancer Res 2012; 195: 151–61.
Lovat F, Valeri N, Croce CM . MicroRNAs in the pathogenesis of cancer. Semin Oncol 2011; 38: 724–33.
Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009; 58: 1375–81.
Wei J, Xie L, Taron M, Rosell R, Liu B . Epigenetic alterations of tumor marker microRNAs: towards new cancer therapies. Drug News Perspect 2010; 23: 655–61.
Yu DC, Li QG, Ding XW, Ding YT . Circulating microRNAs: potential biomarkers for cancer. Int J Mol Sci 2011; 12: 2055–63.
Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, et al. Circulating miR-125b as a marker predicting chemoresistance in breast cancer. PLoS One 2012; 7: e34210.
Ferracin M, Zagatti B, Rizzotto L, Cavazzini F, Veronese A, Ciccone M, et al. MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Mol Cancer 2010; 9: 123.
Graziano F, Canestrari E, Loupakis F, Ruzzo A, Galluccio N, Santini D, et al. Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan. Pharmacogenomics J 2010; 10: 458–64.
Mathe EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, et al. MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res 2009; 15: 6192–200.
Feng J, Sun X, Sun N, Qin S, Li F, Cheng H, et al. XPA A23G polymorphism is associated with the elevated response to platinum-based chemotherapy in advanced non-small cell lung cancer. Acta Biochim Biophys Sin 2009; 41: 429–35.
Yang YQ, Li L, Wang J, Liu XY, Chen XZ, Zhang W, et al. A novel GATA4 loss-of-function mutation associated with congenital ventricular septal defect. Pediatr Cardiol 2012; 33: 539–46.
Kong F, Sun C, Wang Z, Han L, Weng D, Lu Y, et al. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technolog Med Sci 2011; 31: 543–9.
Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y, et al. Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun 2008; 377: 114–9.
Acknowledgements
This work was supported by Zhejiang Province Welfare Technology Applied Research Program (2011C33051) and the National Natural Science Foundation of China (No 31171024).
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Cui, Eh., Li, Hj., Hua, F. et al. Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin 34, 309–313 (2013). https://doi.org/10.1038/aps.2012.125
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DOI: https://doi.org/10.1038/aps.2012.125
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