Expression Signature of <i>E2F1</i> and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors

Lee, Ju Seog; Leem, Sun Hee; Lee, Sang Yeop; Kim, Sang Cheol; Park, Eun Sung; Kim, Sang Bae; Kim, Seon‐Kyu; Kim, Yong June; Kim, Wun-Jae; Chu, In Sun

doi:10.1200/jco.2009.25.0977

Cited by 297 publications

(281 citation statements)

References 35 publications

Supporting

Mentioning

265

Contrasting

Order By: Relevance

“…Expression was independent of clinical stage, grade or the presence of lymph node metastases. These data confirm the conclusion from our previous global analysis of HDAC isoenzyme expression and in silico analyses of publicly available data sets [32][33][34][35][36] that HDAC6 expression is generally variable in urothelial cancers, but that significant overexpression does occur in individual cases, highlighting HDAC6 as a potential target for cancer therapy. Similarly variable results on HDAC6 expression levels have been published for hepatocellular cancers.…”

Section: Discussionsupporting

confidence: 79%

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Rosik

Niegisch

Fischer

et al. 2014

Cancer Biology & Therapy

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 79%

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Rosik

Niegisch

Fischer

et al. 2014

Cancer Biology & Therapy

View full text Add to dashboard Cite

“…Moreover, immunohistochemical analyses indicated that HES1 expression was significantly lower in the muscle invasive bladder carcinomas (MIBC) compared with that in nonmuscle invasive tumors ( Figure 6C and Supplemental Figure 13). Finally, an independent analysis of Oncomine-deposited data (33)(34)(35) confirmed these clinical findings (Supplemental Figure 14). These observations indicate that low levels of HES1 associate with mesenchymal features and invasive properties in human bladder carcinomas.…”

Section: Notch Pathway Inactivation Promotes Bladder Cancer In Micesupporting

confidence: 64%

NOTCH pathway inactivation promotes bladder cancer progression

Maraver¹,

Fernández-Marcos²,

Cash³

et al. 2015

J. Clin. Invest.

View full text Add to dashboard Cite

“…From these studies, it is apparent that low-grade noninvasive and high-grade muscle-invasive tumors harbor distinct gene expression patterns, and that further molecular subsets can be identified within low-grade and high-grade tumors (5,(11)(12)(13)(14). Moreover, a number of gene signatures have been developed that can predict tumor stage, lymph node metastases, and bladder cancer progression (11)(12)(13)(15)(16)(17)(18). There are established gene expression patterns that differentiate lowgrade and high-grade tumors; however, there are little data identifying intrinsic subtypes specifically within high-grade disease.…”

mentioning

confidence: 99%

Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology

Damrauer

Hoadley

Chism

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

760

777

View full text Add to dashboard Cite

We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of highgrade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed "luminal" and "basal-like," which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtypespecific therapies, will be of interest.I n the United States, urothelial carcinoma (UC) of the bladder is the fourth most common malignancy in men and the ninth most common in women, with 72,570 new cases and 15,210 deaths expected in 2013 (1). Bladder cancer is heterogeneous and can be histologically divided into low-grade and high-grade disease. Whereas low-grade tumors are almost invariably noninvasive (Ta), high-grade tumors can be classified based on invasion into the muscularis propria of the bladder, as non-muscle invasive bladder cancer (NMIBC; Tis, Ta, T1) or muscle invasive bladder cancer (MIBC; ≥T2). Low-grade tumors are associated with a high rate of recurrence but an excellent overall prognosis, with a 5-y survival in the range of 90%. In contrast, high-grade MIBC has a relatively poor 5-y overall survival, 68% for T2 and decreasing to 15% for non-organ-confined disease (i.e., pT3 and pT4) (1, 2).Along with divergent pathologies and prognosis, low-grade and high-grade UCs are associated with distinct genetic alterations. For example, low-grade UCs are enriched for activating mutations in fibroblast growth factor 3 (FGFR3), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), and inactivating lysine (K)-specific demethylase 6A (KDM6A) mutations, whereas high-grade, muscle-invasive tumors are enriched for tumor protein p53 (TP53) and retinoblastoma 1 (RB1) pathway alterations (3-10).Several reports have examined the gene expression profiles of primary bladder tumors. From these studies, it is apparent that low-grade noninvasive and high-grade muscle-invasive tumors harbor distinct gene expression patterns, and that further molecular subsets can be identified within low-grade and high-grade tumors (5,(11)(12)(13)(14). Moreover, a number of gene signatures have been developed that can predict tumor stage, lymph node metastases, and bladder cancer progression (11-13, 15-18). There are established gene expression patterns that differentiate lowgrade and high-grade tumors;...

show abstract

Expression Signature of E2F1 and Its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors

Abstract: We present a molecular signature that can predict, at diagnosis, the likelihood of bladder cancer progression and, possibly, lead to improvements in patient therapy.

Cited by 297 publications

References 35 publications

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

Limited efficacy of specific HDAC6 inhibition in urothelial cancer cells

NOTCH pathway inactivation promotes bladder cancer progression

Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology

Contact Info

Product

Resources

About