Abstract
The present study aimed at investigating genetic variations, specific signal pathways, or biological processes of chromosome 1 genes between subtypes and stages of lung cancer and prediction of selected targeting genes for patient survival rate. About 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without caner were integrated from 16 databases and analyzed in the present study. Three (ASPM, CDC20, KIAA1799) or 28 genes significantly up- or down-expressed in four subtypes of lung cancer. The activated cell division and down-regulated immune responses were identified in patients with lung cancer. Keratinocyte development associated genes S100 and SPRR families dominantly up-expressed in SCC and AKT3 and NRAS in SCLC. Subtype-specific genes of ADC, SCC, LCC, or SCLC were also identified. C1orf106, CAPN8, CDC20, COL11A1, CRABP2, and NBPF9 up-expressed at four stages of ADC. Fifty six related with keratinocytes or potassium channels up-expressed in three stages of SCC. CDC20, IL10, ECM1, GABPB2, CRABP2, and COL11A1 significantly predicted the poor overall survival of ADC patients and S100A2 and TIMM17A in SCC patients. Our data indicate that a number of altered chromosome 1 genes have the subtype and stage specificities of lung cancer and can be considered as diagnostic and prognosis biomarkers.









References
Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61, 69–90.
Hensing, T., Chawla, A., Batra, R., & Salgia, R. (2014). A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization. Advances in Experimental Medicine and Biology, 799, 85–117.
Oxnard, G. R., Binder, A., & Janne, P. A. (2013). New targetable oncogenes in non-small-cell lung cancer. Journal of Clinical Oncology, 31, 1097–1104.
Baty, F., Facompre, M., Kaiser, S., et al. (2010). Gene profiling of clinical routine biopsies and prediction of survival in non-small cell lung cancer. American Journal of Respiratory and Critical Care Medicine, 181, 181–188.
Sanchez-Palencia, A., Gomez-Morales, M., Gomez-Capilla, J. A., et al. (2011). Gene expression profiling reveals novel biomarkers in nonsmall cell lung cancer. International Journal of Cancer, 129, 355–364.
Kuner, R., Muley, T., Meister, M., et al. (2009). Global gene expression analysis reveals specific patterns of cell junctions in non-small cell lung cancer subtypes. Lung Cancer, 63, 32–38.
Takeuchi, T., Tomida, S., Yatabe, Y., et al. (2006). Expression profile-defined classification of lung adenocarcinoma shows close relationship with underlying major genetic changes and clinicopathologic behaviors. Journal of Clinical Oncology, 24, 1679–1688.
Lockwood, W. W., Chari, R., Coe, B. P., et al. (2008). DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers. Oncogene, 27, 4615–4624.
Stella, G. M., Luisetti, M., Pozzi, E., & Comoglio, P. M. (2013). Oncogenes in non-small-cell lung cancer: emerging connections and novel therapeutic dynamics. Lancet Respiratory Medecine, 1, 251–261.
Barrett, T., Troup, D. B., Wilhite, S. E., et al. (2007). NCBI GEO: mining tens of millions of expression profiles—database and tools update. Nucleic Acids Research, 35, D760–D765.
Huang, Z. X., Tian, H. Y., Hu, Z. F., Zhou, Y. B., Zhao, J., & Yao, K. T. (2008). GenCLiP: a software program for clustering gene lists by literature profiling and constructing gene co-occurrence networks related to custom keywords. BMC Bioinformatics, 9, 308.
Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., & Hattori, M. (2004). The KEGG resource for deciphering the genome. Nucleic Acids Research, 32, D277–D280.
Therneau, T. (2014). A package for survival analysis in S. R package version 2.37-7, http://CRAN.R-project.org/package=survival.
Gyorffy, B., Surowiak, P., Budczies, J., & Lanczky, A. (2013). Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One, 8, e82241.
Gregory, S. G., Barlow, K. F., McLay, K. E., et al. (2006). The DNA sequence and biological annotation of human chromosome 1. Nature, 441, 315–321.
Nilsson, J., Yekezare, M., Minshull, J., & Pines, J. (2008). The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction. Nature Cell Biology, 10, 1411–1420.
Kato, T., Daigo, Y., Aragaki, M., Ishikawa, K., Sato, M., & Kaji, M. (2012). Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. Journal of Surgical Oncology, 106, 423–430.
Bond, J., Roberts, E., Mochida, G. H., et al. (2002). ASPM is a major determinant of cerebral cortical size. Nature Genetics, 32, 316–320.
Higgins, J., Midgley, C., Bergh, A. M., et al. (2010). Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC Cell Biology, 11, 85.
Finger, E. C., Turley, R. S., Dong, M., How, T., Fields, T. A., & Blobe, G. C. (2008). TbetaRIII suppresses non-small cell lung cancer invasiveness and tumorigenicity. Carcinogenesis, 29, 528–535.
Wei, S., Wang, H., Lu, C., et al. (2014). The activating transcription factor 3 protein suppresses the oncogenic function of mutant p53 proteins. Journal of Biological Chemistry, 289, 8947–8959.
Samten, B. (2013). CD52 as both a marker and an effector molecule of T cells with regulatory action: identification of novel regulatory T cells. Cellular and molecular immunology, 10, 456–458.
Shen, B., Yu, H., Hao, X., Qu, L., Cai, X., & Li, N. (2013). Impact of antimouse CD52 monoclonal antibody on graft’s gammadelta intraepithelial lymphocytes after orthotopic small bowel transplantation in mice. Transplantation, 95, 663–670.
Shipman, M., Lubick, K., Fouchard, D., et al. (2012). Proteomic and systems biology analysis of monocytes exposed to securinine, a GABA(A) receptor antagonist and immune adjuvant. PLoS One, 7, e41278.
Cha, I. S., Castillo, C. S., Nho, S. W., Hikima, J., Aoki, T., & Jung, T. S. (2011). Innate immune response in the hemolymph of an ascidian, Halocynthia roretzi, showing soft tunic syndrome, using label-free quantitative proteomics. Developmental and Comparative Immunology, 35, 809–816.
Park, I. H., Park, S. J., Cho, J. S., et al. (2012). Increased expression of intelectin-1 in nasal polyps. American Journal of Rhinology & Allergy, 26, 274–277.
Park, J. C., Chae, Y. K., Son, C. H., et al. (2008). Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer. Biochemical and Biophysical Research Communications, 365, 221–226.
Chong, I. W., Chang, M. Y., Chang, H. C., et al. (2006). Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer. Oncology Reports, 16, 981–988.
Roche, J., Nasarre, P., Gemmill, R., et al. (2013). Global decrease of histone H3K27 acetylation in ZEB1-induced epithelial to mesenchymal transition in lung cancer cells. Cancers (Basel), 5, 334–356.
Jo, U., Park, K. H., Whang, Y. M., et al. (2014). EGFR endocytosis is a novel therapeutic target in lung cancer with wild-type EGFR. Oncotarget, 5, 1265–1278.
Sundarraj, S., Kannan, S., Thangam, R., & Gunasekaran, P. (2012). Effects of the inhibition of cytosolic phospholipase A(2)alpha in non-small cell lung cancer cells. Journal of Cancer Research and Clinical Oncology, 138, 827–835.
Salama, I., Malone, P. S., Mihaimeed, F., & Jones, J. L. (2008). A review of the S100 proteins in cancer. European Journal of Surgical Oncology, 34, 357–364.
Naz, S., Bashir, M., Ranganathan, P., Bodapati, P., Santosh, V., & Kondaiah, P. (2014). Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3. Carcinogenesis, 35, 14–23.
Tsuta, K., Tanabe, Y., Yoshida, A., et al. (2011). Utility of 10 immunohistochemical markers including novel markers (desmocollin-3, glypican 3, S100A2, S100A7, and Sox-2) for differential diagnosis of squamous cell carcinoma from adenocarcinoma of the Lung. Journal of Thoracic Oncology, 6, 1190–1199.
Vermeij, W. P., & Backendorf, C. (2010). Skin cornification proteins provide global link between ROS detoxification and cell migration during wound healing. PLoS One, 5, e11957.
Woenckhaus, M., Klein-Hitpass, L., Grepmeier, U., et al. (2006). Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers. Journal of Pathology, 210, 192–204.
Fujii, S. I., Shimizu, K., Okamoto, Y., et al. (2013). NKT cells as an ideal Anti-tumor immunotherapeutic. Frontiers in Immunology, 4, 409.
Declerck, S., & Vansteenkiste, J. (2014). Immunotherapy for lung cancer: ongoing clinical trials. Future Oncology, 10, 91–105.
Mollbrink, A., Jawad, R., Vlamis-Gardikas, A., et al. (2014). Expression of thioredoxins and glutaredoxins in human hepatocellular carcinoma: correlation to cell proliferation, tumor size and metabolic syndrome. International Journal of Immunopathology and Pharmacology, 27, 169–183.
Su, D. M., Zhang, Q., Wang, X., et al. (2009). Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy. Molecular Cancer Therapeutics, 8, 1292–1304.
Salio, M., Silk, J. D., Jones, E. Y., & Cerundolo, V. (2014). Biology of CD1- and MR1-restricted T cells. Annual Review of Immunology, 32, 323–366.
Umemura, S., Mimaki, S., Makinoshima, H., et al. (2014). Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. Journal of Thoracic Oncology, 9, 1324–1331.
Zitzmann, K., Vlotides, G., Brand, S., et al. (2012). Perifosine-mediated Akt inhibition in neuroendocrine tumor cells: role of specific Akt isoforms. Endocrine-Related Cancer, 19, 423–434.
Ohashi, K., Sequist, L. V., Arcila, M. E., et al. (2013). Characteristics of lung cancers harboring NRAS mutations. Clinical Cancer Research, 19, 2584–2591.
Kim, B. H., Shenoy, A. R., Kumar, P., Das, R., Tiwari, S., & MacMicking, J. D. (2011). A family of IFN-gamma-inducible 65-kD GTPases protects against bacterial infection. Science, 332, 717–721.
Aoyama, D., Hashimoto, N., Sakamoto, K., et al. (2013). Involvement of TGFbeta-induced phosphorylation of the PTEN C-terminus on TGFbeta-induced acquisition of malignant phenotypes in lung cancer cells. PLoS One, 8, e81133.
Hill, K. S., Erdogan, E., Khoor, A., et al. (2013). Protein kinase Calpha suppresses Kras-mediated lung tumor formation through activation of a p38 MAPK-TGFbeta signaling axis. Oncogene. doi:10.1038/onc.2013.147.
Acknowledgments
The work was supported by Zhongshan Distinguished Professor Grant (XDW), The National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), The Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), Zhejiang Provincial Natural Science Foundation (Z2080988), Zhejiang Provincial Science Technology Department Foundation (2010C14011), and Ministry of Education, Academic Special Science and Research Foundation for PhD Education (20130071110043).
Conflict of interest
The authors declare that they have no competing interests.
Authors’ contributions
YZ contributed the study design and performance, collection of information, analysis, mining, and interpretation of data and writing of the manuscript; JW and LMB contributed the data analyses; HYW contributed the prognosis prediction analyses; XDW contributed the study design and data mining, and preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Table 1
(XLSX 71 kb)
Supplementary Table 2
(XLSX 10 kb)
Supplementary Table 3
(XLSX 113 kb)
Supplementary Table 4
(XLSX 73 kb)
Supplementary Table 5
(XLSX 89 kb)
Supplementary Table 6
(XLSX 14 kb)
Rights and permissions
About this article
Cite this article
Zhang, Y., Wang, H., Wang, J. et al. Global analysis of chromosome 1 genes among patients with lung adenocarcinoma, squamous carcinoma, large-cell carcinoma, small-cell carcinoma, or non-cancer. Cancer Metastasis Rev 34, 249–264 (2015). https://doi.org/10.1007/s10555-015-9558-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10555-015-9558-0