Evidence for a field effect in early prostate cancer (PCa): Gene expression profiles in normal-appearing prostate tissue (NT) adjacent to tumor (T) as predictors of clinical outcome.

5029 Background: We previously identified genes whose expression predicts aggressive PCa (clinical recurrence (cR), prostate cancer death (PCD), adverse pathology) when assessed in histologically heterogeneous tumor foci and in biopsies (Klein ASCO 2012). These results enabled the definition of a multi-gene Genomic Prostate Score (GPS), which has been clinically validated (Cooperberg AUA 2013). There is interest regarding a possible field effect in PCa, i.e. molecular alterations throughout the gland that may influence PCa development. We conducted exploratory analyses to evaluate gene expression, including GPS, in adjacent normal-appearing tissue (NT) for prediction of cR and PCD. Methods: Cohort sampling was used to select 127 patients with and 374 without cR from 2,641 patients treated with RP for T1/T2 PCa. Expression of 732 genes was measured by qRT-PCR separately in T and NT (defined as > 3 mm from T) specimens. GPS (0-100 units) was determined using the genes and algorithm from the validation study. Analysis used Cox proportional hazards models and Storey’s false discovery rate (FDR) control. Results: 410 evaluable patients had paired T and NT. Of the 405 genes which were predictive of outcome in T (FDR < 20%), 289 (71%) showed similar but weaker effects in NT. 47 genes were associated with cR in NT (FDR < 20%), of which 34 also concordantly predicted cR in T (FDR < 20%). GPS assessed in NT significantly predicted time to cR (HR/20 units = 1.8; 95% CI: 1.3-2.4; p< 0.001) and PCD (HR/20 units = 1.9; 95% CI: 1.2-3.0; p = 0.005) but was less predictive than GPS in T (HR/20 units = 4.8 for cR; 95% CI: 3.7-6.2; p < 0.001 and HR/20 units = 6.9 for PCD; 95% CI: 4.4-10.7; p < 0.001). The strongest components of GPS in predicting cR and PCD in NT were stromal response and androgen signaling genes (p < 0.05); proliferation and cellular organization genes did not consistently provide a significant contribution in NT. Conclusions: These data indicate that gene expression profiles, including GPS, can predict outcome in NT, albeit more weakly than in tumor. These findings suggest that there is an underlying field effect associated with the development of aggressive PCa.

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Systematic computational identification of prognostic cytogenetic markers in neuroblastoma

BMC Medical Genomics ◽

10.1186/s12920-019-0620-6 ◽

2019 ◽

Vol 12 (1) ◽

Author(s):

Chao Qin ◽

Xiaoyan He ◽

Yanding Zhao ◽

Chun-Yip Tong ◽

Kenneth Y. Zhu ◽

...

Keyword(s):

Gene Expression ◽

Copy Number ◽

Proportional Hazards ◽

Patient Survival ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Gain Loss ◽

Chromosome Bands

Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor found in children. The frequent gain/loss of many chromosome bands in tumor cells and absence of mutations found at diagnosis suggests that NB is a copy number-driven cancer. Despite the previous work, a systematic analysis that investigates the relationship between such frequent gain/loss of chromosome bands and patient prognosis has yet to be implemented. Methods First, we analyzed two NB CNV datasets to select chromosomal bands with a high frequency of gain or loss. Second, we applied a computational approach to infer sample-specific CNVs for each chromosomal band selected in step 1 based on gene expression data. Third, we applied univariate Cox proportional hazards models to examine the association between the resulting inferred copy number values (iCNVs) and patient survival. Finally, we applied multivariate Cox proportional hazards models to select chromosomal bands that remained significantly associated with prognosis after adjusting for critical clinical variables, including age, stage, gender, and MYCN amplification status. Results Here, we used a computational method to infer the copy number variations (CNVs) of sample-specific chromosome bands from NB patient gene expression profiles. The resulting inferred CNVs (iCNVs) were highly correlated with the experimentally determined CNVs, demonstrating CNVs can be accurately inferred from gene expression profiles. Using this iCNV metric, we identified 58 frequent gain/loss chromosome bands that were significantly associated with patient survival. Furthermore, we found that 7 chromosome bands were still significantly associated with patient survival even when clinical factors, such as MYCN status, were considered. Particularly, we found that the chromosome band chr11p14 has high potential as a novel candidate cytogenetic biomarker for clinical use. Conclusion Our analysis resulted in a comprehensive list of prognostic chromosome bands supported by strong statistical evidence. In particular, the chr11p14 gain event provided additional prognostic value in addition to well-established clinical factors, including MYCN status, and thereby represents a novel candidate cytogenetic biomarker with high clinical potential. Additionally, this computational framework could be readily extended to other cancer types, such as leukemia.

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Genomic Complexity and Recurrent Aberration in Multiple Myeloma: Analysis of a Compendium of aCGH and Gene Expression Profiles.

Blood ◽

10.1182/blood.v112.11.1682.1682 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1682-1682

Author(s):

Wee-Joo Chng ◽

Ian Lee ◽

Victor Jimenez-zepeda ◽

Esteban Braggio ◽

Jonathan Keats ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Proportional Hazards ◽

Expression Profiles ◽

Clinical Status ◽

Gene Expression Profiles ◽

Cox Proportional Hazards ◽

Comparative Genomic ◽

Initial Attempt ◽

Genomic Complexity

Abstract Multiple Myeloma (MM) is the second most prevalent haematological disorder in the US with great recent progress propelled by various technological and therapeutic advances. Nevertheless, the complexity of MM genomes remains inadequately characterized. We have combined high-resolution (44K Agilent) array comparative genomic hybridization (aCGH) and gene expression data with clinical outcomes in an initial attempt at indexing genomic complexity in MM and its clinical implication in 100 MM patients. We enumerated the Number of Aberrations per Tumor (NAPT) as defined by the ADM-1 algorithm available within CGH Analytics. There appear to be no difference in degree of genetic complexity between hyperdiploid and non-hyperdiploid myeloma. Generally, t(11;14) have low NAPT whereas D2 tumors have high NAPT. Amongst the high-risk genetic subtypes, tumors with maf translocations have relatively low NAPT whereas t(4;14) have high NAPT. Whilst a Multivariate Cox Proportional Hazards regression of survival outcome showed little statistical support for popular indicators such as ploidy and TC classification, results for NAPT were considerably more encouraging (p~ 0.07, median survival of 40 months in low complexity vs 18 months in high). Log-rank tests further supported prognosis based on NAPT independent of clinical status and ploidy. To characterize complexity, we clustered aCGH profiles by clinical status, ploidy and TC classification. Clear patterns of aggregation and recurrent aberration were observed suggesting that they were possibly instrument to aberrant gene expression. Indeed, expression of a large proportion of genes approximately 2Mb of the recurrent breakpoints varied significantly between patients carrying aberrations vis-a-viz others that did not. Comparison against known gene sets showed an enrichment for cell-cycle and apoptosis genes. We are presently characterizing several such breakpoint-associated genes for their functional significance.

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The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia

Scientific Reports ◽

10.1038/s41598-019-53563-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Ling Cao ◽

Weilong Zhang ◽

Xiaoni Liu ◽

Ping Yang ◽

Jing Wang ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Proportional Hazards ◽

Expression Profiles ◽

Prognostic Significance ◽

Gene Expression Profiles ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.

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839: Gene Expression Profiles that Underlie the Biological Events Visualized by Magnetic Resonance Spectra (MRS) of Human Prostate Cancer: Choline Kinase

The Journal of Urology ◽

10.1016/s0022-5347(18)38088-1 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 221-222

Author(s):

Sandra M. Gaston ◽

Jonathan G. Rogg ◽

Dang Vu ◽

Jung M. Lee ◽

Dana L. Goldner ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Magnetic Resonance ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Human Prostate ◽

Choline Kinase ◽

Human Prostate Cancer ◽

Magnetic Resonance Spectra

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1100: Gene Expression Profiles of Doxazosin-Treated LNCaP Prostate Cancer Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)38337-x ◽

2004 ◽

Vol 171 (4S) ◽

pp. 290-290

Author(s):

José M. Arencibia ◽

Mónica Del Río ◽

Ana Bonnin ◽

Mónica López-Barahona

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cancer Cells ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Prostate Cancer Cells

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Abstract T MP48: Androgen Suppression in Patients with Prostate Cancer Increases Incidence of Combined Cardiovascular Outcomes

Stroke ◽

10.1161/str.46.suppl_1.tmp48 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Zuber S Ali ◽

Danielle M Greere ◽

Robyn L Shearer ◽

Syed Ali Gardezi ◽

Arshad Jahangir

Keyword(s):

Prostate Cancer ◽

Proportional Hazards ◽

Age Groups ◽

The Elderly ◽

Cox Proportional Hazards ◽

Cardiovascular Outcomes ◽

Elevated Risk ◽

Disease Stage ◽

Cox Proportional Hazards Models ◽

Androgen Suppression

Introduction: Androgen suppression therapy for prostate cancer is controversial due to adverse fatal and non-fatal cardiovascular outcomes reported in some studies. However, effects of androgen suppression on stroke have not been fully assessed in the elderly. Methods: Patients diagnosed with prostate cancer during 2007-2013 in a large community-based healthcare system were identified from the Cancer Registry, electronic records, and billing codes. Those who underwent androgen suppression therapy with Gonadotropin-releasing hormone agonist (GnRH) were propensity-matched to patients treated without androgen suppression therapy by age at cancer diagnosis, race/ethnicity, disease stage and outcome, body mass index and use of surgery, radiation, and chemotherapy. Tests of independence and Cox proportional hazards models were used to examine effects of hormone therapy on acute myocardial infarction (AMI), stroke, and mortality outcomes. Models also adjusted for patient comorbidities. Results: A total of 1282 patients and 641 matched-pairs were identified, with mean diagnosis age of 69 yr and follow-up period of 3.05 yr. Effects of androgen suppression therapy on AMI (P=0.051) and stroke (P=0.062) were of marginal to non-significance, but adjusted-odds of death and combined AMI, stroke, and death were 1.61 times (P=0.002; odds ratio [OR] 95% CI: 1.19-2.18) and 1.70 times (P<0.001; OR 95% CI: 1.26-2.28) greater, respectively, for men with than without androgen suppression. An interaction of androgen suppression and age-group (<65 yr, 65-74 yr, >74 yr) was discovered for combined outcomes, suggesting increased probability of AMI, stroke, and/or death with age (8.6-20.0%; P=0.003) for patients without androgen suppression but elevated risk of outcomes across all age groups (18.3-22.4%; P=0.546) for men treated with androgen suppression therapy. Conclusion: Endogenous androgen suppression presents elevated risk of combined cardiovascular and death outcomes, especially for men <65 yr.

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