Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling

Objectives: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance. Materials and Methods: Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls. Results: Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone. Conclusions: We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic too

No distinct local cuisines among humpback whales: A population diet comparison in the Southern Hemisphere

Southern hemisphere humpback whale (Megaptera novaeangliae, SHHW) breeding populations follow a high-fidelity Antarctic krill (Euphausia superba) diet while feeding in distinct sectors of the Southern Ocean. Their capital breeding life history requires predictable ecosystem productivity to fuel migration and migration-related behaviours. It is therefore postulated that populations feeding in areas subject to the strongest climate change impacts are more likely to show the first signs of a departure from a high-fidelity krill diet. We tested this hypothesis by investigating blubber fatty acid profiles and skin stable isotopes obtained from five SHHW populations in 2019, and comparing them to Antarctic krill stable isotopes sampled in three SHHW feeding areas in the Southern Ocean in 2019. Fatty acid profiles and δ13C and δ15N varied significantly among all five populations, however, calculated trophic positions did not (2.7 to 3.1). Similarly, fatty acid ratios, 16:1ω7c/16:0 and 20:5ω3/22:6ω3 were above 1, showing that whales from all five populations are secondary heterotrophs following an omnivorous diet with a diatom-origin. Thus, evidence for a potential departure from a high-fidelity Antarctic krill diet was not seen in any population. δ13C of all populations were similar to δ13C of krill sampled in productive upwelling areas or the marginal sea-ice zone. Consistency in trophic position and diet origin but significant fatty acid and stable isotope differences demonstrate that the observed variability arises at lower trophic levels. Our results indicate that, at present, there is no evidence of a divergence from a high-fidelity krill diet. Nevertheless, the characteristic isotopic signal of whales feeding in productive upwelling areas, or in the marginal sea-ice zone, implies that future cryosphere reductions could impact their feeding ecology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cyclooxygenase-2 Enzyme Induces the Expression of the α-2,3-Sialyltransferase-3 (ST3Gal-I) in Breast Cancer

Aberrant glycosylation is a common feature of malignant change. Changes in mucin-type O-linked glycosylation in breast cancer can result in the expression of truncated core 1-based sialylated glycans rather than the core 2-based glycans observed in normal mammary epithelium cells. This has been shown, in part, to be due to changes in the expression of glycosyltransferases, including the up-regulation of some sialyltransferases. Using the breast cancer cell line T47D, we have shown that PGE2, one of the final products of the cyclooxygenase-2 (COX-2) pathway, can induce the mRNA expression of the sialyltransferase α-2,3-sialyltransferase-3 (ST3Gal-I), resulting in increased sialyltransferase activity, demonstrated by a reduction in PNA lectin staining. Induction of COX-2 in the MDA-MB-231 breast cancer cell line also results in the increased expression of ST3Gal-I, leading to increased sialylation of the substrate of ST3Gal-I, core 1 Galβ1,3GalNAc. This effect on sialylation could be reversed by the selective COX-2 inhibitor celecoxib. The use of siRNA to knock down COX-2 and overexpression of COX-2 in MDA-MD-231 cells confirmed the involvement of COX-2 in the up-regulation of ST3Gal-I. Moreover, analysis of the expression of ST3Gal-I and COX-2 by 74 primary breast cancers showed a significant correlation between the two enzymes. COX-2 expression has been associated with a number of tumors, including breast cancer, where its expression is associated with poor prognoses. Thus, these results suggest the intriguing possibility that some of the malignant characteristics associated with COX-2 expression may be via the influence that COX-2 exerts on the glycosylation of tumor cells

A benthic bioindicator reveals distinct land and ocean-Based influences in an urbanized coastal embayment.

Biogeochemical maps of coastal regions can be used to identify important influences and inputs that define nearshore environments and biota. Biogeochemical tracers can also track animal movement and their diet, monitor human coastal development, and evaluate the condition of habitats and species. However, the beneficial applications of spatial biogeochemical analysis are hindered by a limited understanding of how tracer distribution is affected by different land and ocean-based influences. To help address these knowledge gaps, we determined the spatial trends of three stable isotopes (δ13C-carbon, δ15N-nitrogen, δ34S-sulfur) and 13 major and trace elements in an urbanized coastal embayment (Moreton Bay, Australia), as incorporated into the muscle tissue of a marine consumer, the eastern king prawn Melicertus plebejus. Results were used to identify unique biochemical regions within the bay and to discuss how spatial patterns in tracers could be used to indicate the relative importance of catchment, urban and offshore drivers in coastal bays. Discriminant analysis identified seven biogeochemical regions that were likely distinguished by variation in catchment, urban, and offshore input, and habitat type. δ13C and δ15N patterns suggested nearshore areas could be distinguished by increased sediment resuspension and higher wastewater inputs from catchments. High inshore lead (Pb) and copper (Cu) concentrations were likely the result of urban input. Arsenic (As) and cadmium (Cd) increased further from shore. This trend implied oceanic influences were a significant control over As and Cd bioavailability. Cobalt (Co) and rare earths were also used to differentiate some nearshore areas, but incongruent distribution patterns in Co suggested it may be less reliable. Overall, results indicated that δ15N, δ13C, Cd, Cu, Pb and rare earth elements were the most reliable tracers to differentiate nearshore and offshore environments, and catchment-based effects. We encourage future studies to consider using a similar multivariate approach in coastal spatial analysis, and to include unrelated tracers that reflect distinct coastal influences

Online prediction of ovarian cancer

In this paper we apply computer learning methods to diagnosing ovarian cancer using the level of the standard biomarker CA125 in conjunction with information provided by mass-spectrometry. We are working with a new data set collectedover a period of 7 years. Using the level of CA125 and mass-spectrometry peaks, our algorithm gives probability predictions for the disease. To estimate classification accuracy we convert probability predictions into strict predictions. Our algorithm makes fewer errors than almost any linear combination of the CA125 level and one peak's intensity (taken on the logscale). To check the power of our algorithm we use it to test the hypothesis that CA125 and the peaks do not contain useful information for the prediction of the disease at a particular time before the diagnosis. Our algorithm produces p-values that are better than those produced by the algorithm that has been previously applied to this data set. Our conclusion is that the proposed algorithm is more reliable for prediction on new data