Role of MicroRNAs in Progression and Recurrence of Early-Stage Lung Adenocarcinoma
DOI:
https://doi.org/10.17140/PRRMOJ-2-108Keywords:
Adenocarcinoma, Biomarker, microRNAs, Non-Small Cell Lung Cancer, Recurrence, TranscriptomeAbstract
Lung cancer is the leading cause of cancer-related death worldwide, and the majority of cases (77%) are not diagnosed until the disease has spread to regional lymph nodes or distant sites. Even among Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma patients who have been diagnosed early and where there has been no spread to lymph nodes, recurrence after surgical intervention is high. Improved understanding of the molecular alterations involved in aggressivity and recurrence of these tumors may provide better biomarkers for the identification of patients who would benefit from adjuvant chemotherapy. By comparing the expression of microRNAs in advanced Stage II/III tumors with those expressed in earlier Stage I tumors, we aimed to identify differentially expressed molecular biomarkers that could underly progression and recurrence of Stage I tumors. This pilot study utilized TaqMan qPCR assays to assess the expression of microRNAs in tumor tissue, matched normal tissue and plasma samples from Stage I and Stage II/III lung adenocarcinoma patients. Seven microRNAs were identified from plasma that could distinguish between patients with Stage I and Stage II/III adenocarcinoma. The up-regulation of miR-29a in plasma of patients with later-stage adenocarcinoma would result in enhanced expression of several molecules involved in integrin signaling, migration and proliferation. Analysis of differential expression of microRNAs in later-stage compared to early-stage lung adenocarcinoma implicates focal adhesion and ECM-receptor pathways in progression and recurrence. Plasma miR-29a is a promising biomarker that can be assessed non-invasively and whose clinical utility should be pursued.
References
WHO. Cancer Fact Sheet 297, 2012. http://www.who.int/me-diacentre/factsheets/fs297/en/ Accessed 2015.
Reed MF, Molloy M, Dalton EL, Howington JA. Survival af-ter resection for lung cancer is the outcome that matters. Am J Surg. 2004; 188: 598-602. doi: http://dx.doi.org/10.1016/j. amjsurg.2004.07.037
Zhang J, Fujimoto J, Wedge DC, et al. Intratumor heteroge-neity in localized lung adenocarcinomas delineated by multi-region sequencing. Science. 2014; 346: 256-259. doi: 10.1126/ science.1256930
Seoane J, De Mattos-Arruda L. The challenge of intratumour heterogeneity in precision medicine. J Intern Med. 2014; 276: 41-51. doi: 10.1111/joim.12240
Tsim S, O’Dowd CA, Milroy R, Davidson S. Staging of non-small cell lung cancer (NSCLC): A review. Respir. Med. 2010; 104: 1767-1774. doi: 10.1016/j.rmed.2010.08.005
Holdenrieder S, Stieber P. Circulating apoptotic markers in the management of non-small cell lung cancer. Cancer Biomark-ers. 2009; 6: 197-210. doi: 10.3233/CBM-2009-0130
Dhillon T, Mauri FA, Bellezza G, et al. Overexpression of the mammalian target of rapamycin: a novel biomarker for poor sur-vival in resected early stage non-small cell lung cancer. J Thorac Oncol. 2010; 5: 314-319. doi: 10.1097/JTO.0b013e3181ce6604
Su WP, Chen YT, Lai WW, Lin CC, Yan JJ, Su WC. Apo-lipoprotein E expression promotes lung adenocarcinoma pro-liferation and migration and as a potential survival marker in lung cancer. Lung Cancer. 2011; 71: 28-33. doi: 10.1016/j. lungcan.2010.04.009
Sholl LM, Barletta JA, Yeap BY, Chirieac LR, Hornick JL. Sox2 protein expression is an independent poor prognostic indi-cator in stage I lung adenocarcinoma. Am J Surg Pathol. 2010; 34: 1193-1198. doi: 10.1097/PAS.0b013e3181e5e024
Woodard GA, Gubens MA, Jahan TM, et al. Prognostic mo-lecular assay might improve identification of patients at risk for recurrence in early-stage non-small-cell lung cancer. Clin Lung Cancer. 2014; 15: 426-432. doi: 10.1016/j.cllc.2014.07.004
Liao J, Yu L, Mei Y, et al. Small nucleolar RNA signatures as biomarkers for non-small-cell lung cancer. Mol. Cancer. 2010; 9: 198-208. doi: 10.1186/1476-4598-9-198
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat. Rev. Cancer. 2006; 6: 259-269. doi: 10.1038/nrc1840
Shen J, Jiang F. Applications of microRNAs in the diagnosis and prognosis of lung cancer. Expert Opin. Med. Diagn. 2012; 6: 197-207.
Ohshima K, Inoue K, Fujiwara A, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One. 2010; 5: e13247. doi: 10.1371/journal.pone.0013247
Hu Z, Chen X, Zhao Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profil-ing predict survival of non-small-cell lung cancer. J. Clin. On-col. 2010; 28: 1721-1726. doi: 10.1200/JCO.2009.24.9342
Kaduthanam S, Gade S, Meister M, et al. Serum miR-142- 3p is associated with early relapse in operable lung adenocarci-noma patients. Lung Cancer. 2013; 80: 223-227. doi: 10.1016/j. lungcan.2013.01.013
Saeed AI, Sharov V, White J, et al. TM4: a free, open-source system for microarray data management and analysis. BioTech-niques. 2003; 34: 374-378.
Heegaard NH, Schetter AJ, Welsh JA, Yoneda M, Bowman ED, Harris CC. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. Int J Cancer. 2012; 130: 1378-1386. doi: 10.1002/ijc.26153
Sakamoto N, Naito Y, Oue N, et al. MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis. Cancer Sci. 2013. doi: 10.1111/cas.12330
Lu L, Xue X, Lan J, Gao Y, et al. MicroRNA-29a upregulates MMP2 in oral squamous cell carcinoma to promote cancer inva-sion and anti-apoptosis. Biomed Pharmacother. 2013; in press.
Weissmann-Brenner A, Kushnir M, Lithwick Yanai G, et al. Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer. Int J Oncol. 2012; 40: 2097-2103. doi: 10.3892/ijo.2012.1403
Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X. Plasma microRNAs are promising novel biomarkers for early detec-tion of colorectal cancer. Int J Cancer. 2010; 127: 118-126. doi: 10.1002/ijc.25007
Yanaihara N, Caplen N, Bowman E, et al. Unique microR-NA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006; 9: 189-198. doi: http://dx.doi.org/10.1016/j. ccr.2006.01.025
Barh D, Jain N, Tiwari S, et al. A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer. BMC Genomics. 2013; 14: S5. doi: 10.1186/1471-2164-14-S6-S5
Boeri M, Verri C, Conte D, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of com-puted tomography detected lung cancer. Proc Natl Acad Sci USA. 2011; 108: 3713-3718. doi: 10.1073/pnas.1100048108
Cheng J, Guo S, Chen S, et al. An extensive network of TET2-targeting MicroRNAs regulates malignant hematopoie-sis. Cell Rep. 2013; 5: 471-481. doi: http://dx.doi.org/10.1016/j. celrep.2013.08.050
Douglas S, Bethune D, Xu Z. Microarray analysis implicates focal adhesion and ECM-receptor pathways in progression of early stage lung adenocarcinoma. Pulm Res Respir Med. 2015; 1: 21-31.
Zhao Y, Zhou T, Li A, Yao H, He F, Wang L, et al. A potential role of collagens expression in distinguishing between prema-lignant and malignant lesions in stomach. Anat Rec (Hoboken). 2009; 292: 692-700. doi: 10.1002/ar.20874
Galvan JA, Garcia-Martinez J, Vazquez-Villa F, et al. Valida-tion of COL11A1/procollagen 11A1 expression in TGF-beta1- activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma. BMC Cancer. 2014; 14: 867. doi: 10.1186/1471-2407-14-867
Wang Z, Liang Z, Liu J, et al. Expression and clinical signifi-cance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung can-cer tissues from patients with non-small cell lung cancer. Onco Targets Ther. 2013; 6: 1437-1444. doi: 10.2147/OTT.S51997
Lavender P, Vandel L, Bannister AJ, Kouzarides T. The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A. Oncogene. 1997; 14: 2721-2728.
Gonzalez L, Eiro N, Gonzalez-Reyes S, et al. Clinical signifi-cance of myosin in colorectal cancer. Ann Diagn Pathol. 2012; 16: 260-266. doi: 10.1016/j.anndiagpath.2011.11.004
Esplugues E, Vega-Ramos J, Cartoixa D, et al. Induction of tumor NK-cell immunity by anti-CD69 antibody therapy. Blood. 2005; 105: 4399-4406.
He S, Chu J, Wu LC, et al. MicroRNAs activate natural kill-er cells through Toll-like receptor signaling. Blood. 2013; 121: 4663-4671. doi: 10.1182/blood-2012-07-441360
Matsui S, Utani A, Takahashi K, Mukoyama Y, Miyachi Y, Matsuyoshi N. Knockdown of Fat2 by siRNA inhibits the migra-tion of human squamous carcinoma cells. J Dermatol Sci. 2008; 51: 207-210. doi: 10.1016/j.jdermsci.2008.04.006
Vie N, Copois V, Bascoul-Mollevi C, et al. Overexpres-sion of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells. Mol Cancer. 2008; 7: 14. doi: 10.1186/1476-4598-7-14
Dalmay T, Edwards DR. MicroRNAs and the hallmarks of cancer. Oncogene. 2006; 25: 6170-6175. doi: 10.1038/ sj.onc.1209911
Lochhead P, Imamura Y, Morikawa T, et al. Insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3) is a marker of unfavourable prognosis in colorectal cancer. Eur J Cancer. 2012; 48: 3405-3413. doi: 10.1016/j.ejca.2012.06.021
Kalathas D, Theocharis DA, Bounias D, et al. Chondroitin synthases I, II, III and chondroitin sulfate glucuronyltransferase expression in colorectal cancer. Mol Med Rep. 2011; 4: 363-368. doi: 10.3892/mmr.2011.431
Schaeffer DF, Owen DR, Lim HJ, et al. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival. BMC Cancer. 2010; 10: 59. doi: 10.1186/1471-2407-10-59
Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic ther-apy? Nat Rev Cancer. 2008; 8: 942-956. doi: 10.1038/nrc2524
Li L, Yu C, Gao H, Li Y. Argonaute proteins: potential bio-markers for human colon cancer. BMC Cancer. 2010; 10: 38. doi: 10.1186/1471-2407-10-38
Lee TV, Sethi MK, Leonardi J, et al. Negative regulation of notch signaling by xylose. PLoS Genet. 2013; 9: e1003547. doi: 10.1371/journal.pgen.1003547
Peng RQ, Wan HY, Li HF, Liu M, Li X, Tang H. MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by targeting UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7. J Biol Chem. 2012; 287: 14301-14309. doi: 10.1074/jbc.M111.337642
Reka AK, Kurapati H, Narala VR, et al. Peroxisome pro-liferator-activated receptor-gamma activation inhibits tumor metastasis by antagonizing Smad3-mediated epithelial-mesen-chymal transition. Mol Cancer Ther. 2010; 9: 3221-3232. doi: 10.1158/1535-7163.MCT-10-0570
Strebhardt K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov. 2010; 9: 643-660. doi: 10.1038/nrd3184
Yu W, Ding X, Chen F, et al. The phosphorylation of SEPT2 on Ser218 by casein kinase 2 is important to hepatoma carci-noma cell proliferation. Mol Cell Biochem. 2009; 325: 61-67. doi: 10.1007/s11010-008-0020-2
Yin Y, Betsuyaku T, Garbow JR, Miao J, Govindan R, Or-nitz DM. Rapid induction of lung adenocarcinoma by fibroblast growth factor 9 signaling through FGF receptor 3. Cancer Res. 2013; 73: 5730-5741. doi: 10.1158/0008-5472.CAN-13-0495
Ohgino K, Soejima K, Yasuda H, et al. Expression of fibro-blast growth factor 9 is associated with poor prognosis in pa-tients with resected non-small cell lung cancer. Lung Cancer. 2014; 83: 90-96. doi: 10.1016/j.lungcan.2013.10.016
Schwarzenbach H. Circulating nucleic acids as biomarkers in breast cancer. Breast Cancer Res. 2013; 15: 211.
Liu XG, Zhu WY, Huang YY, et al. High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med. Oncol. 2012; 29: 618-626. doi: 10.1007/s12032-011-9923-y
Patnaik SK, Kannisto E, Knudsen S, Yendamuri S. Evalua-tion of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical re-section. Cancer Res. 2010; 70: 36-45. doi: 10.1158/0008-5472. CAN-09-3153
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Pulmonary Research and Respiratory Medicine (PRRM) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.
