Development and validation of a 28-gene hypoxia-related prognostic signature for localized prostate cancer

Background Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. Method Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Results A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P  Conclusion A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.</p

Development and validation of a 28-gene hypoxia-related prognostic signature for localized prostate cancer

Background Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer. Method Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON). Results A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients (Log rank test P &lt; .05), with borderline significances achieved in the other two (P &lt; .1). The signature also predicted biochemical recurrence in patients receiving post-prostatectomy radiotherapy (n = 130, P = .007) or definitive radiotherapy alone (n = 248, P = .035). Lastly, the signature predicted metastasis events in a pooled cohort (n = 631, P = .002). Prognostic significance remained after adjusting for clinic-pathological factors and commercially available prognostic signatures. The signature predicted benefit from hypoxia-modifying therapy in bladder cancer patients (intervention-by-signature interaction test P = .0026), where carbogen and nicotinamide was associated with improved survival only in hypoxic tumours. Conclusion A 28-gene hypoxia signature has strong and independent prognostic value for prostate cancer patients.</p

Wet Season Upwelling and Dry Season Chlorophyll-a Describe Interannual Growth Rates of Porites in Southern China

Southern China hosts coral communities in marginal environments that are characterized by low linear extension rates, low coral cover and/or no reef formation, thus providing natural laboratories to study coral communities with below average growth rates. Here we compare the annual linear extension rates over 10 years (range 1.2 to 11.4 mm yr-1) of six Porites sp. coral cores collected from Hong Kong with monthly hydrographic data from the Hong Kong Environmental Protection Department. At all sites, low-density, dry season extension were more variable than high-density, wet season extension and on average, was lower at two of the three sites. We applied multi-variate linear regressions that revealed high-density, wet season band extension to inversely correlate most significantly to temperature (r = -0.39, p<0.01). In contrast, low-density, dry season band extension was more variable and correlated most significantly with dry season chlorophyll-a (Chl-a) (r = 0.64, p<0.001). Additionally, we find that corals at the site with highest dry season Chl-a have the highest dry season extension lengths. Our findings indicate that relative mixing of fresh and salt water in the wet season and primary productivity in the dry season, and their influences on aragonite saturation, are likely to impact interannual coral extension variability in marginal environments