Biomarker research in prostate cancer—towards utility, not futility

Oon, Shereen; Fitzpatrick, John M.; Watson, R. William G.

doi:10.1038/nrurol.2011.11

Cited by 35 publications

(31 citation statements)

References 67 publications

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“…There are several possible reasons for this (reviewed in Oon et al , 2011 ), such as the fact that one prostate can have multiple tumour foci that display different Gleason scores, and it is well known that there is much heterogeneity between tumours that are graded Gleason score 7. We attempted to circumvent some issues involving tumours with Gleason score 7 by restricting analyses to those patients with the more ' extreme ' Gleason scores of ≤ 6 and ≥ 8.…”

Section: Discussionmentioning

confidence: 97%

The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Lose¹,

Lawrence²,

Srinivasan

et al. 2012

Biological Chemistry

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Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

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Section: Discussionmentioning

confidence: 97%

The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Lose¹,

Lawrence²,

Srinivasan

et al. 2012

Biological Chemistry

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show abstract

“…12 In addition, the following abnormal ultrastructural features of the X Sun, N-K Liao, J-J Yu Mitochondrial functional score in prostate cancer mitochondria were observed: swelling, low matrix electron density, cristae that were scarce, disordered, broken or absent, and mitochondrial vacuolation (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Prognostic Value of a Mitochondrial Functional Score in Prostate Cancer

Sun

2012

J Int Med Res

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OBJECTIVE: To evaluate the utility of a mitochondrial functional score in predicting the progress of prostate cancer. METHODS: This retrospective study included 72 patients (mean age 70.1 years) with prostate cancer who were treated by radical prostatectomy between October 2006 and March 2007. The epithelioglandular mitochondrial functional scores were assessed according to the Flameng grading. Patients were divided into six groups (groups 1 – 6) according to their Gleason score (Gleason score 2 – 7, respectively). The correlation between Gleason score and mitochondrial functional score was examined using Pearson's correlation coefficient. RESULTS: The mean mitochondrial functional score was significantly lower in group 6 compared with group 1. An inverse correlation was found between the Gleason and mitochondrial functional scores. At 1 year, significantly fewer patients in group 1 had died (0/15 patients) than in group 6 (2/10 patients); the deaths were cancer-related. CONCLUSIONS: Mitochondrial dysfunction exists in patients with prostate cancer, particularly in cases with a higher degree of malignancy. The mitochondrial functional score, combined with the Gleason score, is beneficial for predicting the progress of prostate cancer.

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“…But biopsy only examines limited sample regions in possible disease sites. Taking prostate cancer for example, even though saturation biopsy is used routinely for prostate cancer evaluation, the overall sensitivity and specificity with prostate biopsy are still very low, approximately 32% and 51%, respectively 71, 72 . In addition, as an invasive approach, biopsy is associated with bleeding, pain, anxiety, possible infections, and other unintended side effects.…”

Section: Targeting Fibronectin For Cancer Imagingmentioning

confidence: 99%

Targeting fibronectin for cancer imaging and therapy

2017

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During cancer progression, the extracellular matrix (ECM) undergoes dramatic changes, which promote cancer cell migration and invasion. In the remodeled tumor ECM, fibronectin (FN) level is upregulated to assist tumor growth, progression, and invasion. FN serves as a central organizer of ECM molecules and mediates the crosstalk between the tumor microenvironment and cancer cells. Its upregulation is correlated with angiogenesis, cancer progression, metastasis, and drug resistance. A number of FN-targeting ligands have been developed for cancer imaging and therapy. Thus far, FN-targeting imaging agents have been tested for nuclear imaging, MRI, and fluorescence imaging, for tumor detection and localization. FN-targeting therapeutics, including nuclear medicine, chemotherapy drugs, cytokines, and photothermal moieties, were also developed in cancer therapy. Because of the prevalence of FN overexpression in cancer, FN targeting imaging agents and therapeutics have the promise of broad applications in the diagnosis, treatment, and image-guided interventions of many types of cancers. This review will summarize current understanding on the role of FN in cancer, discuss the design and development of FN-targeting agents, and highlight the applications of these FN-targeting agents in cancer imaging and therapy.

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Biomarker research in prostate cancer—towards utility, not futility

Cited by 35 publications

References 67 publications

The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Prognostic Value of a Mitochondrial Functional Score in Prostate Cancer

Targeting fibronectin for cancer imaging and therapy

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