Prognostic and predictive biomarkers in prostate cancer

Kontos, Christos K.; Adamopoulos, Panagiotis G.; Scorilas, Andreas

doi:10.1586/14737159.2015.1110022

Cited by 28 publications

(23 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated PSA levels are common when prostatic inflammation is present [21][22][23]. Recent reports indicate that PSA is a doubleedged sword when used as a biomarker of prostate cancer (reviewed in [24]) as it also serves as an indicator of inflammation based on subsequent biopsies that did not show cancer [22]. As a result, the findings in the current study, along with previous studies, suggest that circulating PSA levels serve as an indicator of inflammation in the prostate and therefore, are not necessarily a specific biomarker for cancer.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago

et al. 2017

View full text Add to dashboard Cite

Background Serum prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. Methods HHV-8 serostatus was determined among men with elevated serum PSA (≥4ng/ml; n=168, no prostate cancer on biopsy) and age-matched controls (PSA<4ng/ml; n=234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Results Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95% CI 1.48 – 4.29, P=00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10 and IL-13 indicating a Th2 immune response. Conclusions We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA.

show abstract

Section: Discussionmentioning

confidence: 99%

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago

et al. 2017

View full text Add to dashboard Cite

show abstract

“…From the genetic point of view, PCa can be considered a collection of cancers characterized by sets of molecular alterations that may underlie the clinically variable behavior of the disease and support the need to identify subgroups of patients with different prognoses [3]. Recently, the prognostic value of many molecular and genetic factors has been investigated, including the loss of PTEN or Akt mutations [4–6]. The prognostic significance of the TMPRSS2-ERG (T2E) fusion gene, a specific chromosomal rearrangement found in 50–70% of PCa that involves the androgen-responsive promoter of TMPRSS2 and the ETS transcription factor family gene ERG, has been evaluated, but the results are not conclusive [7–10].…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor 1 receptor affects the survival of primary prostate cancer patients depending on TMPRSS2-ERG status

et al. 2017

View full text Add to dashboard Cite

BackgroundProstate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. Therefore, it is necessary to identify molecular alterations to define new therapeutic strategies based on the risk of progression. In this study, the prognostic relevance of the insulin-like growth factor (IGF) system was examined in molecular subtypes defined by TMPRSS2-ERG (T2E) gene fusion within a series of patients with primary localized PCa.MethodsA cohort of 270 formalin-fixed and paraffin-embedded (FFPE) primary PCa samples from patients with more than 5 years’ follow-up was collected. IGF-1R, IGF-1, IGFBP-3 and INSR expression was analyzed using quantitative RT-PCR. The T2E status and immunohistochemical ERG findings were considered in the analyses. The association with both biochemical and clinical progression-free survival (BPFS and PFS, respectively) was evaluated for the different molecular subtypes using the Kaplan-Meier proportional risk log-rank test and the Cox proportional hazards model.ResultsAn association between IGF-1R overexpression and better BPFS was found in T2E-negative patients (35.3% BPFS, p-value = 0.016). Multivariate analysis demonstrated that IGF-1R expression constitutes an independent variable in T2E-negative patients [HR: 0.41. CI 95% (0.2–0.82), p = 0.013]. These data were confirmed using immunohistochemistry of ERG as subrogate of T2E. High IGF-1 expression correlated with prolonged BPFS and PFS independent of the T2E status.Conclusions IGF-1R, a reported target of T2E, constitutes an independent factor for good prognosis in T2E-negative PCa. Quantitative evaluation of IGF-1/IGF-1R expression combined with molecular assessment of T2E status or ERG protein expression represents a useful marker for tumor progression in localized PCa.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3356-8) contains supplementary material, which is available to authorized users.

show abstract

“…Prostate cancer (PCa) is one of the most common malignant tumors in the male worldwide, and the second leading cause of cancer-related death among men in America (1)(2)(3)(4). Despite the development in PCa early diagnosis and treatment methods (5), metastasis and tumor relapse still remains a serious problem for the patients long-term survival, and the mechanisms involved in PCa progression and metastasis are not fully understood. Several studies have shown that inhibition of apoptosis is the most critical factor for tumorigenesis in PCa (6,7).…”

Section: Introductionmentioning

confidence: 99%

Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells

Zhu

et al. 2016

Oncology Reports

View full text Add to dashboard Cite

Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear. In the present study, we aimed to understand the relationships between Bif-1 expression and PCa development. The mRNA and protein expression levels of Bif-1 in PCa cell lines, benign prostatic hyperplasia (BPH) (n=100) and PCa tissues (n=100, including low Gleason-scored PCa n=43 and high Gleason-scored PCa n=57) were detected and the effects of Bif-1 overexpression on the apoptosis, proliferation and migration in LNCaP cells were explored. Bif-1 mRNA levels of PCa cell lines were analyzed by real-time PCR and the protein levels were detected by western blotting. Bif-1 expression in BPH and PCa samples was detected by immunohistochemistry. To build Bif-1 overexpression PCa cells, Bif-1 gene was transfected into LNCaP cells by pcDNA3.1(+)‑Bif-1 vector. Cell apoptosis was detected by flow cytometric analysis, cell proliferation measured by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay and cell migration was analyzed by wound‑healing assay. The results proved that Bif-1 is downregulated in both PCa cell lines (P<0.01) and clinical samples (P<0.05), and Bif-1 expression is suppressed with the cancer progression (BPH vs. PCa P<0.01, and low Gleason-scored PCa vs. high Gleason-scored PCa P<0.05). Overexpression of Bif-1 could significantly inhibit cell proliferation (P<0.05) and enhancing PCa cell apoptosis (P<0.05), but it did not affect the migration ability (P>0.05). Our findings give strong evidence that Bif-1 is involved in PCa tumorigenesis and acts as a suppressor in PCa progression, and may have significance in understanding the process of PCa development.

show abstract

Prognostic and predictive biomarkers in prostate cancer

Cited by 28 publications

References 77 publications

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago

Insulin-like growth factor 1 receptor affects the survival of primary prostate cancer patients depending on TMPRSS2-ERG status

Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells

Contact Info

Product

Resources

About