Show simple item record

Expression profiling of cervical cancers in I ndian women at different stages to identify gene signatures during progression of the disease

dc.contributor.authorThomas, Ashaen_US
dc.contributor.authorMahantshetty, Umeshen_US
dc.contributor.authorKannan, Sadhanaen_US
dc.contributor.authorDeodhar, Kedaren_US
dc.contributor.authorShrivastava, Shyam K.en_US
dc.contributor.authorKumar‐sinha, Chandanen_US
dc.contributor.authorMulherkar, Ritaen_US
dc.date.accessioned2013-12-04T18:57:15Z
dc.date.available2015-01-05T13:54:43Zen_US
dc.date.issued2013-12en_US
dc.identifier.citationThomas, Asha; Mahantshetty, Umesh; Kannan, Sadhana; Deodhar, Kedar; Shrivastava, Shyam K.; Kumar‐sinha, Chandan ; Mulherkar, Rita (2013). "Expression profiling of cervical cancers in I ndian women at different stages to identify gene signatures during progression of the disease." Cancer Medicine 2(6): 836-848.en_US
dc.identifier.issn2045-7634en_US
dc.identifier.issn2045-7634en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/101800
dc.description.abstractCervical cancer is the second most common cancer among women worldwide, with developing countries accounting for >80% of the disease burden. Although in the West, active screening has been instrumental in reducing the incidence of cervical cancer, disease management is hampered due to lack of biomarkers for disease progression and defined therapeutic targets. Here we carried out gene expression profiling of 29 cervical cancer tissues from I ndian women, spanning International Federation of Gynaecology and Obstetrics ( FIGO ) stages of the disease from early lesion (IA and IIA) to progressive stages (IIB and IIIA–B), and identified distinct gene expression signatures. Overall, metabolic pathways, pathways in cancer and signaling pathways were found to be significantly upregulated, while focal adhesion, cytokine–cytokine receptor interaction and WNT signaling were downregulated. Additionally, we identified candidate biomarkers of disease progression such as SPP 1, proliferating cell nuclear antigen ( PCNA ), STK 17A, and DUSP 1 among others that were validated by quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ) in the samples used for microarray studies as well in an independent set of 34 additional samples. Integrative analysis of our results with other cervical cancer profiling studies could facilitate the development of multiplex diagnostic markers of cervical cancer progression. Cervical cancer is the leading cause of cancer deaths among women in I ndia, yet it remains poorly characterized at molecular level. This study provides one of the largest molecular profiling efforts from this region involving cervical cancer tissues from well‐defined clinical stages to identify molecular signatures of disease progression, as well as identify novel biomarkers distinguishing early and advanced disease. We expect this study to serve as a template for larger studies, including those based on high‐throughput sequencing, to help develop robust biomarkers of disease progression and potentially identify actionable therapeutic targets.en_US
dc.publisherGLOBOCANen_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherMicroarrayen_US
dc.subject.otherBiomarkeren_US
dc.subject.otherCervical Canceren_US
dc.subject.otherExpression Profilingen_US
dc.subject.otherReal‐Time PCRen_US
dc.titleExpression profiling of cervical cancers in I ndian women at different stages to identify gene signatures during progression of the diseaseen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelHematology and Oncologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/101800/1/cam4152.pdf
dc.identifier.doi10.1002/cam4.152en_US
dc.identifier.sourceCancer Medicineen_US
dc.identifier.citedreferenceSong, J. Y., J. K. Lee, N. W. Lee, H. H. Jung, S. H. Kim, and K. W. Lee. 2008. Microarray analysis of normal cervix, carcinoma in situ, and invasive cervical cancer: identification of candidate genes in pathogenesis of invasion in cervical cancer. Int. J. Gynecol. Cancer 18: 1051 – 1059.en_US
dc.identifier.citedreferenceKim, H. E., D. G. Kim, K. J. Lee, J. G. Son, M. Y. Song, Y. M. Park, et al. 2012. Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PLoS One 7: e43223.en_US
dc.identifier.citedreferenceShrestha, S., L. J. Wilmeth, J. Eyer, and C. B. Shuster. 2012. PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis. Mol. Biol. Cell 23: 1196 – 1207.en_US
dc.identifier.citedreferenceHuang, Z., Y. Cheng, P. M. Chiu, F. M. Cheung, J. M. Nicholls, D. L. Kwong, et al. 2012. Tumor suppressor Alpha B‐crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression‐associated properties. Oncogene 31: 3709 – 3720.en_US
dc.identifier.citedreferenceTaron, M., R. Rosell, E. Felip, P. Mendez, J. Souglakos, M. S. Ronco, et al. 2004. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum. Mol. Genet. 13: 2443 – 2449.en_US
dc.identifier.citedreferenceClark‐Knowles, K. V., A. M. O'Brien, and J. I. Weberpals. 2010. BRCA1 as a therapeutic target in sporadic epithelial ovarian cancer. J. Oncol. 2010: 891059.en_US
dc.identifier.citedreferenceWeber, G. F., G. S. Lett, and N. C. Haubein. 2010. Osteopontin is a marker for cancer aggressiveness and patient survival. Br. J. Cancer 103: 861 – 869.en_US
dc.identifier.citedreferenceLe, Q. T., P. D. Sutphin, S. Raychaudhuri, S. C. Yu, D. J. Terris, H. S. Lin, et al. 2003. Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clin. Cancer Res. 9: 59 – 67.en_US
dc.identifier.citedreferenceOgbureke, K. U., P. M. Weinberger, S. W. Looney, L. Li, and L. W. Fisher. 2012. Expressions of matrix metalloproteinase‐9 (MMP‐9), dentin sialophosphoprotein (DSPP), and osteopontin (OPN) at histologically negative surgical margins may predict recurrence of oral squamous cell carcinoma. Oncotarget 3: 286 – 298.en_US
dc.identifier.citedreferenceLiersch, R., J. Gerss, C. Schliemann, M. Bayer, C. Schwoppe, C. Biermann, et al. 2012. Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients. Blood 119: 5215 – 5220.en_US
dc.identifier.citedreferenceCho, H., S. W. Hong, Y. J. Oh, M. A. Kim, E. S. Kang, J. M. Lee, et al. 2008. Clinical significance of osteopontin expression in cervical cancer. J. Cancer Res. Clin. Oncol. 134: 909 – 917.en_US
dc.identifier.citedreferenceMaga, G., and U. Hubscher. 2003. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J. Cell Sci. 116: 3051 – 3060.en_US
dc.identifier.citedreferenceAstudillo, H., T. Lopez, S. Castillo, P. Gariglio, and L. Benitez. 2003. p53, Bcl‐2, PCNA expression, and apoptotic rates during cervical tumorigenesis. Ann. N. Y. Acad. Sci. 1010: 771 – 774.en_US
dc.identifier.citedreferenceBranca, M., M. Ciotti, C. Giorgi, D. Santini, L. Di Bonito, S. Costa, et al. 2007. Up‐regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high‐risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer. Eur. J. Obstet. Gynecol. Reprod. Biol. 130: 223 – 231.en_US
dc.identifier.citedreferenceTahan, S. R., D. S. Neuberg, A. Dieffenbach, and L. Yacoub. 1993. Prediction of early relapse and shortened survival in patients with breast cancer by proliferating cell nuclear antigen score. Cancer 71: 3552 – 3559.en_US
dc.identifier.citedreferenceZhong, W., J. Peng, H. He, D. Wu, Z. Han, X. Bi, et al. 2008. Ki‐67 and PCNA expression in prostate cancer and benign prostatic hyperplasia. Clin. Invest. Med. 31: E8 – E15.en_US
dc.identifier.citedreferenceWang, K., M. Zhang, Y. Y. Qian, Z. Y. Ding, J. H. Lv, and H. H. Shen. 2011. Imbalanced expression of mitogen‐activated protein kinase phosphatase‐1 and phosphorylated extracellular signal‐regulated kinases in lung squamous cell carcinoma. J. Zhejiang Univ. Sci. B 12: 828 – 834.en_US
dc.identifier.citedreferenceMoncho‐Amor, V., I. Ibanez de Caceres, E. Bandres, B. Martinez‐Poveda, J. L. Orgaz, I. Sanchez‐Perez, et al. 2011. DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non‐small‐cell lung cancer. Oncogene 30: 668 – 678.en_US
dc.identifier.citedreferenceSchuebel, K. E., N. Movilla, J. L. Rosa, and X. R. Bustelo. 1998. Phosphorylation‐dependent and constitutive activation of Rho proteins by wild‐type and oncogenic Vav‐2. EMBO J. 17: 6608 – 6621.en_US
dc.identifier.citedreferenceBrantley‐Sieders, D. M., G. Zhuang, D. Vaught, T. Freeman, Y. Hwang, D. Hicks, et al. 2009. Host deficiency in Vav2/3 guanine nucleotide exchange factors impairs tumor growth, survival, and angiogenesis in vivo. Mol. Cancer Res. 7: 615 – 623.en_US
dc.identifier.citedreferenceSanjo, H., T. Kawai, and S. Akira. 1998. DRAKs, novel serine/threonine kinases related to death‐associated protein kinase that trigger apoptosis. J. Biol. Chem. 273: 29066 – 29071.en_US
dc.identifier.citedreferenceGiefing, M., J. I. Martin‐Subero, K. Kiwerska, M. Jarmuz, R. Grenman, R. Siebert, et al. 2008. Characterization of homozygous deletions in laryngeal squamous cell carcinoma cell lines. Cancer Genet. Cytogenet. 184: 38 – 43.en_US
dc.identifier.citedreferenceMao, P., M. Jardine, L. Niemaszyk, J. Haghkerdar, E. Yang, E. G. yanco, et al. 2012. The novel protein kinase STK17A is a direct p53 target gene that mediates response to genotoxic and nutritional stress in a cancer cell context‐dependent manner. P. 72 in Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research, Chicago, IL, 31 March–4 April 2012. AACR; Cancer Res, Philadelphia (PA).en_US
dc.identifier.citedreferenceRonai, Z., Y. M. Yang, S. Y. Fuchs, V. Adler, M. Sardana, and M. Herlyn. 1998. ATF2 confers radiation resistance to human melanoma cells. Oncogene 16: 523 – 531.en_US
dc.identifier.citedreferenceXu, Y., Z. Liu, and K. Guo. 2012. The effect of JDP2 and ATF2 on the epithelial‐mesenchymal transition of human pancreatic cancer cell lines. Pathol. Oncol. Res. 18: 571 – 577.en_US
dc.identifier.citedreferenceZito, C. R., L. B. Jilaveanu, V. Anagnostou, D. Rimm, G. Bepler, S. M. Maira, et al. 2012. Multi‐level targeting of the phosphatidylinositol‐3‐kinase pathway in non‐small cell lung cancer cells. PLoS One 7: e31331.en_US
dc.identifier.citedreferenceWeber, G. L., M. O. Parat, Z. A. Binder, G. L. Gallia, and G. J. Riggins. 2011. Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells. Oncotarget 2: 833 – 849.en_US
dc.identifier.citedreferenceFu, Y., Q. Zhang, C. Kang, K. Zhang, J. Zhang, P. Pu, et al. 2009. Inhibitory effects of adenovirus mediated COX‐2, Akt1 and PIK3R1 shRNA on the growth of malignant tumor cells in vitro and in vivo. Int. J. Oncol. 35: 583 – 591.en_US
dc.identifier.citedreferenceGlobocan. 2008. Cancer incidence, mortality and prevalence worldwide in 2008. GLOBOCAN, Available at: http://globocan.iarc.fr.en_US
dc.identifier.citedreferenceDikshit, R., P. C. Gupta, C. Ramasundarahettige, V. Gajalakshmi, L. Aleksandrowicz, R. Badwe, et al. 2012. Cancer mortality in India: a nationally representative survey. Lancet 379: 1807 – 1816.en_US
dc.identifier.citedreferenceKjaer, S. K., A. J. van den Brule, J. E. Bock, P. A. Poll, G. Engholm, M. E. Sherman, et al. 1996. Human papillomavirus – the most significant risk determinant of cervical intraepithelial neoplasia. Int. J. Cancer 65: 601 – 606.en_US
dc.identifier.citedreferenceGolub, T. R., D. K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J. P. Mesirov, et al. 1999. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286: 531 – 537.en_US
dc.identifier.citedreferenceAlizadeh, A. A., M. B. Eisen, R. E. Davis, C. Ma, I. S. Lossos, A. Rosenwald, et al. 2000. Distinct types of diffuse large B‐cell lymphoma identified by gene expression profiling. Nature 403: 503 – 511.en_US
dc.identifier.citedreferenceGruvberger, S., M. Ringner, Y. Chen, S. Panavally, L. H. Saal, A. Borg, et al. 2001. Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res. 61: 5979 – 5984.en_US
dc.identifier.citedreferenceSorlie, T., C. M. Perou, R. Tibshirani, T. Aas, S. Geisler, H. Johnsen, et al. 2001. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA 98: 10869 – 10874.en_US
dc.identifier.citedreferenceReyal, F., M. H. van Vliet, N. J. Armstrong, H. M. Horlings, K. E. de Visser, M. Kok, et al. 2008. A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer. Breast Cancer Res. 10: R93.en_US
dc.identifier.citedreferencePaik, S., S. Shak, G. Tang, C. Kim, J. Baker, M. Cronin, et al. 2004. A multigene assay to predict recurrence of tamoxifen‐treated, node‐negative breast cancer. N. Engl. J. Med. 351: 2817 – 2826.en_US
dc.identifier.citedreferencevan‘t Veer, L. J., H. Dai, M. J. van de Vijver, Y. D. He, A. A. Hart, M. Mao, et al. 2002. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415: 530 – 536.en_US
dc.identifier.citedreferenceSorensen, K. D., and T. F. Orntoft. 2010. Discovery of prostate cancer biomarkers by microarray gene expression profiling. Expert Rev. Mol. Diagn. 10: 49 – 64.en_US
dc.identifier.citedreferenceWilliams, G. H., P. Romanowski, L. Morris, M. Madine, A. D. Mills, K. Stoeber, et al. 1998. Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc. Natl. Acad. Sci. USA 95: 14932 – 14937.en_US
dc.identifier.citedreferenceFreeman, A., L. S. Morris, A. D. Mills, K. Stoeber, R. A. Laskey, G. H. Williams, et al. 1999. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin. Cancer Res. 5: 2121 – 2132.en_US
dc.identifier.citedreferenceChen, Y., C. Miller, R. Mosher, X. Zhao, J. Deeds, M. Morrissey, et al. 2003. Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Res. 63: 1927 – 1935.en_US
dc.identifier.citedreferenceHarima, Y., S. Sawada, Y. Miyazaki, K. Kin, H. Ishihara, M. Imamura, et al. 2003. Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival. Am. J. Clin. Oncol. 26: e80 – e85.en_US
dc.identifier.citedreferenceRajkumar, T., N. Vijayalakshmi, K. Sabitha, S. Shirley, G. Selvaluxmy, M. V. Bose, et al. 2009. A 7 gene expression score predicts for radiation response in cancer cervix. BMC Cancer 9: 365.en_US
dc.identifier.citedreferenceWong, Y. F., D. S. Sahota, T. H. Cheung, K. W. Lo, S. F. Yim, T. K. Chung, et al. 2006. Gene expression pattern associated with radiotherapy sensitivity in cervical cancer. Cancer J. 12: 189 – 193.en_US
dc.identifier.citedreferenceHuang, L., M. Zheng, Q. M. Zhou, M. Y. Zhang, Y. H. Yu, J. P. Yun, et al. 2012. Identification of a 7‐gene signature that predicts relapse and survival for early stage patients with cervical carcinoma. Med. Oncol. 4: 2911 – 2918.en_US
dc.identifier.citedreferenceRajkumar, T., K. Sabitha, N. Vijayalakshmi, S. Shirley, M. V. Bose, G. Gopal, et al. 2011. Identification and validation of genes involved in cervical tumorigenesis. BMC Cancer 11: 80.en_US
dc.identifier.citedreferenceBenjamini, Y., and Y. Hochberg. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57: 289 – 300.en_US
dc.identifier.citedreferenceBiewenga, P., M. R. Buist, P. D. Moerland, E. Ver Loren van Themaat, A. H. van Kampen, F. J. ten Kate, et al. 2008. Gene expression in early stage cervical cancer. Gynecol. Oncol. 108: 520 – 526.en_US
dc.identifier.citedreferenceAhn, W. S., S. M. Bae, J. M. Lee, S. E. Namkoong, S. J. Han, Y. L. Cho, et al. 2004. Searching for pathogenic gene functions to cervical cancer. Gynecol. Oncol. 93: 41 – 48.en_US
dc.identifier.citedreferencePerez‐Plasencia, C., G. Vazquez‐Ortiz, R. Lopez‐Romero, P. Pina‐Sanchez, J. Moreno, and M. Salcedo. 2007. Genome wide expression analysis in HPV16 cervical cancer: identification of altered metabolic pathways. Infect. Agent Cancer 2: 16.en_US
dc.identifier.citedreferenceSantin, A. D., F. Zhan, E. Bignotti, E. R. Siegel, S. Cane, S. Bellone, et al. 2005. Gene expression profiles of primary HPV16‐ and HPV18‐infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Virology 331: 269 – 291.en_US
dc.identifier.citedreferenceWong, Y. F., T. H. Cheung, G. S. Tsao, K. W. Lo, S. F. Yim, V. W. Wang, et al. 2006. Genome‐wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray. Int. J. Cancer 118: 2461 – 2469.en_US
dc.identifier.citedreferenceCheng, Q., W. M. Lau, S. K. Tay, S. H. Chew, T. H. Ho, and K. M. Hui. 2002. Identification and characterization of genes involved in the carcinogenesis of human squamous cell cervical carcinoma. Int. J. Cancer 98: 419 – 426.en_US
dc.identifier.citedreferenceShadeo, A., R. Chari, K. M. Lonergan, A. Pusic, D. Miller, T. Ehlen, et al. 2008. Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia. BMC Genomics 9: 64.en_US
dc.identifier.citedreferenceGius, D., M. C. Funk, E. Y. Chuang, S. Feng, P. C. Huettner, L. Nguyen, et al. 2007. Profiling microdissected epithelium and stroma to model genomic signatures for cervical carcinogenesis accommodating for covariates. Cancer Res. 67: 7113 – 7123.en_US
dc.identifier.citedreferenceConesa‐Zamora, P. 2013. Role of cell cycle biomarkers in human papillomavirus related uterine lesions. Curr. Pharm. Des. 19: 1412 – 1424.en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


Files in this item

Show simple item record

Remediation of Harmful Language

The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.

Accessibility

If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.