Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers.
Dohun Pyeon,Michael A. Newton,Paul F. Lambert,Johan A. den Boon,Srikumar Sengupta,Carmen J. Marsit,Craig D. Woodworth,Joseph P. Connor,Thomas H. Haugen,Elaine M. Smith,Karl T. Kelsey,Lubomir P. Turek,Paul Ahlquist +12 more
TLDR
Findings in primary human tumors provide novel biomarkers for early detection of HPV(+) and HPV(-) cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV (+) cancers.Abstract:
Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+ HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV− HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+ HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV− HNC. Moreover, HPV+ cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV+ HNC and HPV− HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV− cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. [Cancer Res 2007;67(10):4605–19]read more
Citations
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Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene.
TL;DR: Combined knowledge of multiple genes' function from in vitro experiments together with meta-analysis of multiple cancers can deliver compact and robust signatures suitable for clinical application.
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Human Papillomavirus in Head and Neck Cancer: Its Role in Pathogenesis and Clinical Implications
TL;DR: Human papillomavirus-positive cancers are clinically distinct when compared with HPV-negative cancers with regard to treatment response and survival outcome, with tumor HPV-positivity being a favorable prognostic biomarker.
Journal ArticleDOI
Heterogeneity of tumor-induced gene expression changes in the human metabolic network
Jie Hu,Jason W. Locasale,Jason H. Bielas,Jason H. Bielas,Jacintha O'Sullivan,Kieran Sheahan,Lewis C. Cantley,Lewis C. Cantley,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Dennis Vitkup +10 more
TL;DR: Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues, and many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes, which are potential targets for anticancer therapy.
Journal ArticleDOI
Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer
Randall J. Kimple,Molly A. Smith,Grace C. Blitzer,Alexandra D. Torres,Joshua A. Martin,Robert Z. Yang,Chimera R. Peet,Laurel D. Lorenz,Kwangok P. Nickel,Aloysius J. Klingelhutz,Paul F. Lambert,Paul M. Harari +11 more
TL;DR: These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC, and suggest that low levels of normally functioning p53 in HPV+, which could be activated by radiation, leading to cell death.
Journal ArticleDOI
The emerging role of CXCL10 in cancer (Review)
TL;DR: This review focuses on current research elucidating the emerging role of CXCL10 in the pathogenesis of cancer, and examines its role as a potential biomarker and therapeutic target for related human malignancies.
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