Tumor Biol. DOI 10.1007/s13277-015-3366-6
RESEARCH ARTICLE
Prognostic value of microRNA-10b overexpression in peripheral blood mononuclear cells of nonsmall-cell lung cancer patients Yun-Long Yang 1 & Lu-Ping Xu 2 & Feng-Lin Zhuo 1 & Tian-You Wang 1
Received: 22 January 2015 / Accepted: 19 March 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Abstract We examined microRNA (miRNA)-10b expression in peripheral blood mononuclear cells (PBMCs) of nonsmall-cell lung cancer (NSCLC) patients for its clinical value. A group of 74 patients confirmed with NSCLC were recruited as case group and 52 healthy volunteers as control group. PBMCs were isolated from all subjects, and miRNA10b expression level in these cells was measured by reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between miRNA-10b expression levels and the clinical and pathological characteristics of NSCLC was obtained. The miRNA-10b expression level in NSCLS patients is markedly higher than control subjects (P < 0.01). Analysis of receiver operating characteristic (ROC) curve estimated the peak diagnostic sensitivity of miRNA-10b at 86.5 % and specificity at 76.9 %. NSCLC patients were divided into high expression group (64 patients) and low expression group (10 patients). Further analysis showed that miRNA-10b expression levels in PBMCs correlated with lymph node metastasis, distant metastasis, and TNM classification (all P60 years, lymph node and distant metastases, and stage III–IV carcinoma were risk factors for poor prognosis in
* Tian-You Wang [email protected] 1
Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District Beijing 100050, People’s Republic of China
2
Department of Thoracic Surgery, The Affiliated Hospital of Beihua University, Jilin 132011, People’s Republic of China
NSCLC patients (all P60 v. ≤60 years) Smoking history (>10 vs ≤10 packs/year)
2.763 0.478 1.113 0.290
0.716 0.339 0.365 0.445
14.889 1.988 9.306 0.424
0.000 0.159 0.002 0.515
15.848 1.613 3.043 1.336
3.894–64.489 0.830–3.137 1.489–6.221 0.558–3.199
Pathogenic site (right vs left) Histology (squamous cell carcinoma vs adenocarcinoma) Tumor size (≥3 vs 60 years, lymph node metastasis, distant metastasis, and stage III–IV carcinoma were found to be the major risk factors for poor prognosis of NSCLC. These results implicate that miRNA-10b expression level in PBMCs might be a potentially high value screening tool for early detection of NSCLC. In summary, we provide strong evidence that high expression of miRNA-10b in PBMC samples of NSCLC patients correlated with poor patient outcomes. Measurement of miRNA-10b expression in PBMCs distinguished NSCLC patients from cancer-free subjects with high sensitivity and specificity, suggesting that miRNA-10b expression in PBMCs might be a prognostic factor for NSCLC. Nevertheless, further validation of miRNA-10b status in a larger population, and identification of other aberrantly expressed miRNAs in PBMCs, is required to expand the tools available for improving patient outcomes in NSCLC patients. Acknowledgments We would like to acknowledge the reviewers for their helpful comments on this paper. Conflicts of interest The authors have declared that no existing competing interests.
Tumor Biol.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012;148(1– 2):259–72. Xie Y, Todd NW, Liu Z, Zhan M, Fang H, Peng H, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010;67(2):170–6. Schabath MB, Nguyen A, Wilson P, Sommerer KR, Thompson ZJ, Chiappori AA. Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer patients. Lung Cancer. 2014;86(1): 14–21. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin Chem. 2008;54(10):1696–704. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6(3): 482–8. van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56. Cui EH, Li HJ, Hua F, Wang B, Mao W, Feng XR, et al. Serum microrna 125b as a diagnostic or prognostic biomarker for advanced nsclc patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin. 2013;34(2):309–13. Jin H, Yu Y, Chrisler WB, Xiong Y, Hu D, Lei C. Delivery of MicroRNA-10b with polylysine nanoparticles for inhibition of breast cancer cell wound healing. Breast Cancer (Auckl). 2012;6: 9–19. Zhang J, Xu L, Yang Z, Lu H, Hu D, Li W, et al. MicroRNA-10b indicates a poor prognosis of non-small cell lung cancer and targets E-cadherin. Clin Transl Oncol. 2014;17(3):209–14.
11.
Liu Y, Li M, Zhang G, Pang Z. MicroRNA-10b overexpression promotes non-small cell lung cancer cell proliferation and invasion. Eur J Med Res. 2013;18:41. 12. M PN. World medical association publishes the revised declaration of Helsinki. Natl Med J India. 2014;27(1):56. 13. Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18(6):1059–68. 14. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P, et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568–77. 15. Crino L, Weder W, van Meerbeeck J, Felip E, Group EGW. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v103–15. 16. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008;358(11):1118–28. 17. Soria JC, Shepherd FA, Douillard JY, Wolf J, Giaccone G, Crino L, et al. Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol. 2009;20(10):1674– 81. 18. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008;118(7):2600–8. 19. Mittal RD, Gangwar R, George GP, Mittal T, Kapoor R. Investigative role of pre-microRNAs in bladder cancer patients: a case-control study in North India. DNA Cell Biol. 2011;30(6):401–6. 20. Shen Y, Tang D, Yao R, Wang M, Wang Y, Yao Y, et al. Microrna expression profiles associated with survival, disease progression, and response to gefitinib in completely resected non-small-cell lung cancer with egfr mutation. Med Oncol. 2013;30(4):750. 21. Villanueva A, Hoshida Y, Toffanin S, Lachenmayer A, Alsinet C, Savic R, et al. New strategies in hepatocellular carcinoma: genomic prognostic markers. Clin Cancer Res. 2010;16(19):4688–94.
RESEARCH ARTICLE
Prognostic value of microRNA-10b overexpression in peripheral blood mononuclear cells of nonsmall-cell lung cancer patients Yun-Long Yang 1 & Lu-Ping Xu 2 & Feng-Lin Zhuo 1 & Tian-You Wang 1
Received: 22 January 2015 / Accepted: 19 March 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015
Abstract We examined microRNA (miRNA)-10b expression in peripheral blood mononuclear cells (PBMCs) of nonsmall-cell lung cancer (NSCLC) patients for its clinical value. A group of 74 patients confirmed with NSCLC were recruited as case group and 52 healthy volunteers as control group. PBMCs were isolated from all subjects, and miRNA10b expression level in these cells was measured by reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between miRNA-10b expression levels and the clinical and pathological characteristics of NSCLC was obtained. The miRNA-10b expression level in NSCLS patients is markedly higher than control subjects (P < 0.01). Analysis of receiver operating characteristic (ROC) curve estimated the peak diagnostic sensitivity of miRNA-10b at 86.5 % and specificity at 76.9 %. NSCLC patients were divided into high expression group (64 patients) and low expression group (10 patients). Further analysis showed that miRNA-10b expression levels in PBMCs correlated with lymph node metastasis, distant metastasis, and TNM classification (all P60 years, lymph node and distant metastases, and stage III–IV carcinoma were risk factors for poor prognosis in
* Tian-You Wang [email protected] 1
Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95, Yongan Road, Xicheng District Beijing 100050, People’s Republic of China
2
Department of Thoracic Surgery, The Affiliated Hospital of Beihua University, Jilin 132011, People’s Republic of China
NSCLC patients (all P60 v. ≤60 years) Smoking history (>10 vs ≤10 packs/year)
2.763 0.478 1.113 0.290
0.716 0.339 0.365 0.445
14.889 1.988 9.306 0.424
0.000 0.159 0.002 0.515
15.848 1.613 3.043 1.336
3.894–64.489 0.830–3.137 1.489–6.221 0.558–3.199
Pathogenic site (right vs left) Histology (squamous cell carcinoma vs adenocarcinoma) Tumor size (≥3 vs 60 years, lymph node metastasis, distant metastasis, and stage III–IV carcinoma were found to be the major risk factors for poor prognosis of NSCLC. These results implicate that miRNA-10b expression level in PBMCs might be a potentially high value screening tool for early detection of NSCLC. In summary, we provide strong evidence that high expression of miRNA-10b in PBMC samples of NSCLC patients correlated with poor patient outcomes. Measurement of miRNA-10b expression in PBMCs distinguished NSCLC patients from cancer-free subjects with high sensitivity and specificity, suggesting that miRNA-10b expression in PBMCs might be a prognostic factor for NSCLC. Nevertheless, further validation of miRNA-10b status in a larger population, and identification of other aberrantly expressed miRNAs in PBMCs, is required to expand the tools available for improving patient outcomes in NSCLC patients. Acknowledgments We would like to acknowledge the reviewers for their helpful comments on this paper. Conflicts of interest The authors have declared that no existing competing interests.
Tumor Biol.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012;148(1– 2):259–72. Xie Y, Todd NW, Liu Z, Zhan M, Fang H, Peng H, et al. Altered miRNA expression in sputum for diagnosis of non-small cell lung cancer. Lung Cancer. 2010;67(2):170–6. Schabath MB, Nguyen A, Wilson P, Sommerer KR, Thompson ZJ, Chiappori AA. Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer patients. Lung Cancer. 2014;86(1): 14–21. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin Chem. 2008;54(10):1696–704. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ. miR1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol. 2011;6(3): 482–8. van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11(9):644–56. Cui EH, Li HJ, Hua F, Wang B, Mao W, Feng XR, et al. Serum microrna 125b as a diagnostic or prognostic biomarker for advanced nsclc patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin. 2013;34(2):309–13. Jin H, Yu Y, Chrisler WB, Xiong Y, Hu D, Lei C. Delivery of MicroRNA-10b with polylysine nanoparticles for inhibition of breast cancer cell wound healing. Breast Cancer (Auckl). 2012;6: 9–19. Zhang J, Xu L, Yang Z, Lu H, Hu D, Li W, et al. MicroRNA-10b indicates a poor prognosis of non-small cell lung cancer and targets E-cadherin. Clin Transl Oncol. 2014;17(3):209–14.
11.
Liu Y, Li M, Zhang G, Pang Z. MicroRNA-10b overexpression promotes non-small cell lung cancer cell proliferation and invasion. Eur J Med Res. 2013;18:41. 12. M PN. World medical association publishes the revised declaration of Helsinki. Natl Med J India. 2014;27(1):56. 13. Brambilla E, Travis WD, Colby TV, Corrin B, Shimosato Y. The new World Health Organization classification of lung tumours. Eur Respir J. 2001;18(6):1059–68. 14. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P, et al. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568–77. 15. Crino L, Weder W, van Meerbeeck J, Felip E, Group EGW. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v103–15. 16. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008;358(11):1118–28. 17. Soria JC, Shepherd FA, Douillard JY, Wolf J, Giaccone G, Crino L, et al. Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors. Ann Oncol. 2009;20(10):1674– 81. 18. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008;118(7):2600–8. 19. Mittal RD, Gangwar R, George GP, Mittal T, Kapoor R. Investigative role of pre-microRNAs in bladder cancer patients: a case-control study in North India. DNA Cell Biol. 2011;30(6):401–6. 20. Shen Y, Tang D, Yao R, Wang M, Wang Y, Yao Y, et al. Microrna expression profiles associated with survival, disease progression, and response to gefitinib in completely resected non-small-cell lung cancer with egfr mutation. Med Oncol. 2013;30(4):750. 21. Villanueva A, Hoshida Y, Toffanin S, Lachenmayer A, Alsinet C, Savic R, et al. New strategies in hepatocellular carcinoma: genomic prognostic markers. Clin Cancer Res. 2010;16(19):4688–94.
