Skip to main content
Top
Published in: Tumor Biology 4/2015

01-04-2015 | Research Article

Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening

Authors: Jin-shan Yang, Bao-jian Li, Hua-wei Lu, Yu Chen, Chuan Lu, Rui-xia Zhu, Si-hai Liu, Qing-ting Yi, Jing Li, Chun-hui Song

Published in: Tumor Biology | Issue 4/2015

Login to get access

Abstract

Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S. GLOBOCAN 2012 v1. 0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. 2014. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S. GLOBOCAN 2012 v1. 0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. 2014.
2.
go back to reference Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA, editors. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings: Elsevier; 2008. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA, editors. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings: Elsevier; 2008.
3.
go back to reference Crino L, Weder W, Van Meerbeeck J, Felip E. 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:v103–15.CrossRefPubMed Crino L, Weder W, Van Meerbeeck J, Felip E. 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:v103–15.CrossRefPubMed
4.
go back to reference Swensen SJ, Jett JR, Sloan JA, Midthun DE, Hartman TE, Sykes A-M, et al. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med. 2002;165:508–13.CrossRefPubMed Swensen SJ, Jett JR, Sloan JA, Midthun DE, Hartman TE, Sykes A-M, et al. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med. 2002;165:508–13.CrossRefPubMed
6.
go back to reference Yu L, Todd NW, Xing L, Xie Y, Zhang H, Liu Z, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010;127:2870–8.CrossRefPubMedPubMedCentral Yu L, Todd NW, Xing L, Xie Y, Zhang H, Liu Z, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer. 2010;127:2870–8.CrossRefPubMedPubMedCentral
7.
go back to reference Crawford M, Brawner E, Batte K, Yu L, Hunter M, Otterson G, et al. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun. 2008;373:607–12.CrossRefPubMed Crawford M, Brawner E, Batte K, Yu L, Hunter M, Otterson G, et al. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun. 2008;373:607–12.CrossRefPubMed
8.
go back to reference Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, et al. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS One. 2014;9:e87780.CrossRefPubMedPubMedCentral Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, et al. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS One. 2014;9:e87780.CrossRefPubMedPubMedCentral
9.
go back to reference Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci. 2007;104:15805–10.CrossRefPubMedPubMedCentral Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci. 2007;104:15805–10.CrossRefPubMedPubMedCentral
11.
go back to reference Zhong M, Ma X, Sun C, Chen L. MicroRNAs reduce tumor growth and contribute to enhance cytotoxicity induced by gefitinib in non-small cell lung cancer. Chem Biol Interact. 2010;184:431–8.CrossRefPubMed Zhong M, Ma X, Sun C, Chen L. MicroRNAs reduce tumor growth and contribute to enhance cytotoxicity induced by gefitinib in non-small cell lung cancer. Chem Biol Interact. 2010;184:431–8.CrossRefPubMed
12.
go back to reference Nielsen LB, Wang C, Sørensen K, Bang-Berthelsen CH, Hansen L, Andersen M-LM, et al. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Experiment Diab Res. 2012;2012. Nielsen LB, Wang C, Sørensen K, Bang-Berthelsen CH, Hansen L, Andersen M-LM, et al. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Experiment Diab Res. 2012;2012.
13.
go back to reference Bidzhekov K, Gan L, Denecke B, Rostalsky A, Hristov M, Koeppel TA, et al. microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans. Thromb Haemost. 2012;107:619.CrossRefPubMed Bidzhekov K, Gan L, Denecke B, Rostalsky A, Hristov M, Koeppel TA, et al. microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans. Thromb Haemost. 2012;107:619.CrossRefPubMed
14.
go back to reference Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23:814–24.CrossRefPubMedPubMedCentral Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23:814–24.CrossRefPubMedPubMedCentral
15.
go back to reference Zhou X, Zhao F, Wang Z-N, Song Y-X, Chang H, Chiang Y, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 2012;27:447.PubMed Zhou X, Zhao F, Wang Z-N, Song Y-X, Chang H, Chiang Y, et al. Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 2012;27:447.PubMed
16.
go back to reference Li R, Qian N, Tao K, You N, Wang X, Dou K. MicroRNAs involved in neoplastic transformation of liver cancer stem cells. J Exp Clin Cancer Res. 2010;29:169.CrossRefPubMedPubMedCentral Li R, Qian N, Tao K, You N, Wang X, Dou K. MicroRNAs involved in neoplastic transformation of liver cancer stem cells. J Exp Clin Cancer Res. 2010;29:169.CrossRefPubMedPubMedCentral
17.
go back to reference Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, et al. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 2010;14:1170–9.CrossRefPubMed Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C, et al. Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 2010;14:1170–9.CrossRefPubMed
18.
go back to reference Song Y-X, Yue Z-Y, Wang Z-N, Xu Y-Y, Luo Y, Xu H-M, et al. MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation. Mol Cancer. 2011;10:1.CrossRefPubMedPubMedCentral Song Y-X, Yue Z-Y, Wang Z-N, Xu Y-Y, Luo Y, Xu H-M, et al. MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation. Mol Cancer. 2011;10:1.CrossRefPubMedPubMedCentral
19.
go back to reference Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–5.CrossRefPubMed Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67:6130–5.CrossRefPubMed
20.
go back to reference Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.CrossRefPubMed
21.
go back to reference Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, et al. Over-and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 2009;34:1069–75.PubMed Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, et al. Over-and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 2009;34:1069–75.PubMed
22.
go back to reference Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.CrossRefPubMed Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.CrossRefPubMed
23.
go back to reference Katada T, Ishiguro H, Kuwabara Y, Kimura M, Mitui A, Mori Y, et al. microRNA expression profile in undifferentiated gastric cancer. Int J Oncol. 2009;34:537.PubMed Katada T, Ishiguro H, Kuwabara Y, Kimura M, Mitui A, Mori Y, et al. microRNA expression profile in undifferentiated gastric cancer. Int J Oncol. 2009;34:537.PubMed
24.
go back to reference Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci. 2008;105:3903–8.CrossRefPubMedPubMedCentral Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci. 2008;105:3903–8.CrossRefPubMedPubMedCentral
25.
go back to reference Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.CrossRefPubMed Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–6.CrossRefPubMed
26.
go back to reference Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non–small cell lung cancer risk. Cancer Res. 2008;68:8535–40.CrossRefPubMedPubMedCentral Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non–small cell lung cancer risk. Cancer Res. 2008;68:8535–40.CrossRefPubMedPubMedCentral
27.
go back to reference Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713–22.CrossRefPubMed Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713–22.CrossRefPubMed
28.
go back to reference Capodanno A, Boldrini L, Proietti A, Alì G, Pelliccioni S, Niccoli C, et al. Let-7g and miR-21 expression in non-small cell lung cancer: correlation with clinicopathological and molecular features. Int J Oncol. 2013;43:765–74.PubMed Capodanno A, Boldrini L, Proietti A, Alì G, Pelliccioni S, Niccoli C, et al. Let-7g and miR-21 expression in non-small cell lung cancer: correlation with clinicopathological and molecular features. Int J Oncol. 2013;43:765–74.PubMed
29.
go back to reference Seike M, Goto A, Okano T, Bowman ED, Schetter AJ, Horikawa I, et al. MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci. 2009;106:12085–90.CrossRefPubMedPubMedCentral Seike M, Goto A, Okano T, Bowman ED, Schetter AJ, Horikawa I, et al. MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc Natl Acad Sci. 2009;106:12085–90.CrossRefPubMedPubMedCentral
30.
go back to reference Zhang J-g, Wang J-j, Zhao F, Liu Q, Jiang K, Yang G-h. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 2010;411:846–52.CrossRefPubMed Zhang J-g, Wang J-j, Zhao F, Liu Q, Jiang K, Yang G-h. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta. 2010;411:846–52.CrossRefPubMed
31.
go back to reference Zhao Y, Jia H, Zhou H, Dong Q, Fu L, Yan Z, et al. Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR. Zhonghua gan zang bing za zhi= Zhonghua ganzangbing zazhi= Chinese J Hepatol. 2009;17:526–530. Zhao Y, Jia H, Zhou H, Dong Q, Fu L, Yan Z, et al. Identification of metastasis-related microRNAs of hepatocellular carcinoma in hepatocellular carcinoma cell lines by quantitative real time PCR. Zhonghua gan zang bing za zhi= Zhonghua ganzangbing zazhi= Chinese J Hepatol. 2009;17:526–530.
32.
go back to reference Huang J, Wang Y, Guo Y, Sun S. Down‐regulated microRNA‐152 induces aberrant DNA methylation in hepatitis B virus–related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 2010;52:60–70.CrossRefPubMed Huang J, Wang Y, Guo Y, Sun S. Down‐regulated microRNA‐152 induces aberrant DNA methylation in hepatitis B virus–related hepatocellular carcinoma by targeting DNA methyltransferase 1. Hepatology. 2010;52:60–70.CrossRefPubMed
33.
go back to reference Zhu A, Xia J, Zuo J, Jin S, Zhou H, Yao L, et al. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer. Med Oncol. 2012;29:2701–9.CrossRefPubMed Zhu A, Xia J, Zuo J, Jin S, Zhou H, Yao L, et al. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in gastric cancer. Med Oncol. 2012;29:2701–9.CrossRefPubMed
34.
go back to reference Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci. 2008;105:13556–61.CrossRefPubMedPubMedCentral Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci. 2008;105:13556–61.CrossRefPubMedPubMedCentral
35.
go back to reference Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17:7574–83.CrossRefPubMed Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17:7574–83.CrossRefPubMed
36.
go back to reference Song Y, Xu Y, Wang Z, Chen Y, Yue Z, Gao P, et al. MicroRNA‐148b suppresses cell growth by targeting cholecystokinin‐2 receptor in colorectal cancer. Int J Cancer. 2012;131:1042–51.CrossRefPubMed Song Y, Xu Y, Wang Z, Chen Y, Yue Z, Gao P, et al. MicroRNA‐148b suppresses cell growth by targeting cholecystokinin‐2 receptor in colorectal cancer. Int J Cancer. 2012;131:1042–51.CrossRefPubMed
Metadata
Title
Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancer screening
Authors
Jin-shan Yang
Bao-jian Li
Hua-wei Lu
Yu Chen
Chuan Lu
Rui-xia Zhu
Si-hai Liu
Qing-ting Yi
Jing Li
Chun-hui Song
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2938-1

Other articles of this Issue 4/2015

Tumor Biology 4/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine