OJCD  Vol.7 No.3 , September 2017
Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood

Background: Lung cancer is among the most common cancers. Search is ongoing to find biomarkers to improve the diagnosis lung cancer techniques in early stages. In this study we evaluate the sensitivity and specificity of the MUC1 and CEA gene expressions in the peripheral blood of non-small cell lung cancer (NSCLC). Material and Methods: This study was done in Masih Daneshvari Hospital, Tehran, Iran and was case/control study that conducted on 30 NSCLC patients and 30 healthy controls. Peripheral blood was collected and total RNA was extracted then cDNA was synthesized. Sample was separately assessed by real time PCR. Results: The expression of CEA gen was positive in 24 patients indicating 80% sensitivity for this marker. The expression of CEA gen was positive in 9 controls out of 30 each. A statistically significant difference was detected between patients and healthy controls with regard to CEA mRNA expression (P < 0.001). The MUC1 gen expressed in 20 out of 30 patients, while it expressed in 3 controls. The difference in MUC1 mRNA expression was statistically significant between NSCLC patients and healthy controls (P < 0.001). Conclusion: MUC1 and CEA are molecular biomarkers with relatively favorable sensitivity for primary diagnosis of NSCLC.

Cite this paper: Bahrami, N. , Jamaati, H. , Nia, J. , Tabarsi, P. , Fakharian, A. , Emami, H. , Sharifynia, S. , Abniki, M. , Mohamadnia, A. (2017) Two Molecular Markers of Early Non-Small Cell Lung Carcinoma Based on Gene Expression in Peripheral Blood. Open Journal of Clinical Diagnostics, 7, 91-102. doi: 10.4236/ojcd.2017.73010.

[1]   Keith, R.L. and Miller, Y.E. (2013) Lung Cancer Chemoprevention: Current Status and Future Prospects. Nature Reviews Clinical Oncology, 10, 334-343.

[2]   Gettinger, S.N., Kowanetz, M., Koeppen, H., Wistuba, I.I., Kockx, M., Kadel, E.E., et al. (2015) Molecular, Immune and Histopathological Characterization of NSCLC Based on PDL1 Expression on Tumor and Immune Cells and Association with Response to the Anti-PDL1 Antibody MPDL3280A. American Society of Clinical Oncology, 33, 3015.

[3]   Raponi, M., Dossey, L., Jatkoe, T., Wu, X., Chen, G., Fan, H., et al. (2009) MicroRNA Classifiers for Predicting Prognosis of Squamous Cell Lung Cancer. Cancer Research, 69, 5776-5783.

[4]   Milroy, R. (2007) New American College of Chest Physicians Lung Cancer Guidelines: An Important Addition to the Lung Cancer Guidelines Armamentarium. Chest Journal, 132, 744-746.

[5]   Thomas, C. and Sweep, C. (2001) Serum Tumor Markers: Past, State of the Art, and Future. The International Journal of Biological Markers, 16, 73-86.

[6]   Zheng, H., Chen, Q., Ye, Y. and Huang, W. (2008) mRNA Expression of CK19 and CEA in Peripheral Blood of Patients with Breast Cancer Detected by Real-Time Quantitative PCR. Zhonghua Yi Xue Za Zhi, 88, 2267-2270.

[7]   Perez, C.A. and Brady, L.W. (2011) Radiation Oncology: Management Decisions. Lippincott Williams & Wilkins, Philadelphia.

[8]   Franchina, T., Amodeo, V., Bronte, G., Savio, G., Ricciardi, G.R., Picciotto, M., et al. (2014) Circulating miR-22, miR-24 and miR-34a as Novel Predictive Biomarkers to Pemetrexed-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer. Journal of Cellular Physiology, 229, 97-99.

[9]   Esquela-Kerscher, A. and Slack, F.J. (2006) Oncomirs—microRNAs with a Role in Cancer. Nature Reviews Cancer, 6, 259-269.

[10]   Tian, T., Shu, Y., Chen, J., Hu, Z., Xu, L., Jin, G., et al. (2009) A Functional Genetic Variant in microRNA-196a2 Is Associated with Increased Susceptibility of Lung Cancer in Chinese. Cancer Epidemiology and Prevention Biomarkers, 18, 1183-1187.

[11]   Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., et al. (2004) Human microRNA Genes Are Frequently Located at Fragile Sites and Genomic Regions Involved in Cancers. Proceedings of the National academy of Sciences of the United States of America, 101, 2999-3004.

[12]   Benedíková, A., Srovnal, J., Szkorupa, M., Skalicky, P., Chudácek, J., Bohanes, T., et al. (2012) Biomarkers in the Detection of Minimal Systemic Dissemination in Lung Cancer Patients. Rozhledy v Chirurgii: Mesicnik Ceskoslovenske Chirurgicke Spolecnosti, 91, 209-215.

[13]   Gerhard, M., Juhl, H., Kalthoff, H., Schreiber, H.W., Wagener, C. and Neumaier, M. (1994) Specific Detection of Carcinoembryonic Antigen-Expressing Tumor Cells in Bone Marrow Aspirates by Polymerase Chain Reaction. Journal of Clinical Oncology, 12, 725-729.

[14]   Bahrami, N. , Gholami, M., Jamaati, H.R., Mohamadnia, A., Dargahi, H., Kazempour Dizaji, M., Khosravi, A., Heshmatnia, J., Vahabi, P. and Bahrami, N.A. (2016) Expression of Two Essential mRNA Biomarker in the Peripheral Blood as Possible Biomarkers for Diagnosis of Non-Small Cell Lung Carcinoma. Minerva Pneumologica, 55, 31-36.

[15]   Grunnet, M. and Sorensen, J. (2012) Carcinoembryonic antigen (CEA) as Tumor Marker in Lung Cancer. Lung Cancer, 76, 138-143.

[16]   Zhu, G., Liu, D., Wang, X. and Chen, J. (2004) Detection of CK19 and CEA mRNA Expression for the Diagnosis of Peripheral Blood Micrometastases in Patients with Non-Small Cell Lung Cancer. Chinese Journal of Lung Cancer, 7, 226-229.

[17]   Li, X., Hu, Y., Zhang, S. and Zheng, S. (2004) Combined Detection of CEA mRNA and CK 19 mRNA in Peripheral Blood Cells of Patients with Lung Cancer. Chinese Journal of Oncology, 26, 382-384.

[18]   Peterson, J.A., Scallan, C.D., Ceriani, R.L. and Hamosh, M. (2001) Structural and Functional Aspects of Three Major Glycoproteins of the Human Milk Fat Globule Membrane. Bioactive Components of Human Milk, Springer, New York, 179-187.

[19]   Hu, X.F., Yang, E., Li, J. and Xing, P.X. (2006) MUC1 Cytoplasmic Tail: A Potential Therapeutic Target for Ovarian Carcinoma. Expert Review of Anticancer Therapy, 6, 1261-1271.

[20]   Leroy, X., Buisine, M.-P., Leteurtre, E., Aubert, S., Buob, D., Porchet, N., et al. (2006) MUC1 EMA, A Key Molecule of Carcinogenesis? Annales de Pathologie, 26, 257-266.

[21]   Li, Y. and Cozzi, P. (2007) MUC1 Is a Promising Therapeutic Target for Prostate Cancer Therapy. Current Cancer Drug Targets, 7, 259-271.

[22]   Mahanta, S., Fessler, S.P., Park, J. and Bamdad, C. (2008) A Minimal Fragment of MUC1* Mediates Growth of Cancer Cells. PLoS One, 3, e2054.

[23]   Hikita, S.T., Kosik, K.S., Clegg, D.O. and Bamdad, C. (2008) MUC1* Mediates the Growth of Human Pluripotent Stem Cells. PloS One, 3, e3312.

[24]   Fessler, S.P., Wotkowicz, M.T., Mahanta, S.K. and Bamdad, C. (2009) MUC1* Is a Determinant of Trastuzumab (Herceptin) Resistance in Breast Cancer Cells. Breast Cancer Research and Treatment, 118, 113.

[25]   Karimi, S., Mohamadnia, A., Nadji, S.A., Yadegarazari, R., Khosravi, A., Bahrami, N., et al. (2015) Expression of Two Basic mRNA Biomarkers in Peripheral Blood of Patients with Non-Small Cell Lung Cancer Detected by Real-Time rt-PCR, Individually and Simultaneously. Iranian Biomedical Journal, 19, 17.

[26]   Ghadimi, K., Bahrami, N., Fathi, M., Farzanegan, B., Naji, T., Emami, M., et al. (2017) 56, 10.23736/S0026-4954.16.01773-9) D. Diagnostic Value of LunX mRNA and CEA mRNA Expression in Pleural Fluid of Patients with Non-Small Cell Lung Cancer, Minerva Pneumologica.

[27]   Karimi, S., Bahrami, N., Sharifi, K., Daustany, M., Baghbani-Arani, F., Kazempour, M., et al. (2017) Investigating Gene Expression Level of MUC1 and CEA in Pleural Fluid of NSCLC Lung Cancer Patients with Real-Time RT-PCR Method. Minerva Pneumologica, 56, 18-24.

[28]   Moshref Behzad, N., Bahrami, N., Farzanegan, B., Fathi, M., Zareh Karizi, S. and Mohamadnia, A. (2017) Expression of CK19-mRNA and CEA-mRNA Biomarkers in Pleural Fluid of Patients with Non-Small Cell Lung Cancer. Minerva Pneumologica, 56, 78-83.

[29]   Bates, J., Rutherford, R., Divilly, M., Finn, J., Grimes, H., O'Muircheartaigh, I., et al. (1997) Clinical Value of CYFRA 21.1, Carcinoembryonic Antigen, Neurone-Specific Enolase, Tissue Polypeptide Specific Antigen and Tissue Polypeptide Antigen in the Diagnosis of Lung Cancer. European Respiratory Journal, 10, 2535-2538.

[30]   Paone, G., De Angelis, G., Munno, R., Pallotta, G., Bigioni, D., Saltini, C., et al. (1995) Discriminant Analysis on Small Cell Lung Cancer and Non-Small Cell Lung Cancer by Means of NSE and CYFRA-21.1. European Respiratory Journal, 8, 1136-1140.

[31]   Iwao, K., Watanabe, T., Fujiwara, Y., Takami, K., Kodama, K., Higashiyama, M., et al. (2001) Isolation of a Novel Human Lung-Specific Gene, LUNX, a Potential Molecular Marker for Detection of Micrometastasis in Non-Small-Cell Lung Cancer. International Journal of Cancer, 91, 433-437.<::AID-IJC1059>3.0.CO;2-B

[32]   Jamaati, H., Bahrami, N., Abniki, M., Tabarsi, P., Farzanegan, B., Doroudinia, A., et al. (2016) Real-Time RT-PCR Detection of HCN4 and ADAM8 Genes in Ventilator-Associated Pneumonia Patients Hospitalized in Intensive Care Unit. Journal of Cellular and Molecular Anesthesia, 1, 163-167.

[33]   Wallace, M.B., Block, M.I., Gillanders, W., Ravenel, J., Hoffman, B.J., Reed, C.E., et al. (2005) Accurate Molecular Detection of Non-Small Cell Lung Cancer Metastases in Mediastinal Lymph Nodes Sampled by Endoscopic Ultrasound-Guided Needle Aspiration. CHEST Journal, 127, 430-437.

[34]   Mohamadnia, A., Karimi, S., Yadegar Azari, R., Naji, S.A., Khosravi, A., Bahrami, N., et al. (2016) Expression of CK19 Gene in Patients with Lung Cancer and Its Comparison with Carcinoembryonic Antigen in Peripheral Blood. Journal of Payavard Salamat, 9, 459-468.

[35]   Saintigny, P., Coulon, S., Kambouchner, M., Ricci, S., Martinot, E., Danel, C., et al. (2005) Real-Time RT-PCR Detection of CK19, CK7 and MUC1 mRNA for Diagnosis of Lymph Node Micrometastases in Non Small Cell Lung Carcinoma. International Journal of Cancer, 115, 777-782.

[36]   Kufe, D.W. (2009) Mucins in Cancer: Function, Prognosis and Therapy. Nature Reviews Cancer, 9, 874-885.

[37]   Li, J., Hu, Y.-M., Du, Y.-J., Zhu, L.-R., Qian, H., Wu, Y., et al. (2014) Expressions of MUC1 and Vascular Endothelial Growth Factor mRNA in Blood Are Biomarkers for Predicting Efficacy of Gefitinib Treatment in Non-Small Cell Lung Cancer. BMC Cancer, 14, 848.