Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer

Abstract

Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases.electron | cryotomography | platelet | microtubule | cancer

Quantifying Variability of Manual Annotation in Cryo-Electron Tomograms

“…The bottleneck for many cryoET studies lies in tomogram segmentation, a technique used to separate structurally complex tomograms into their individual components for visualization (Volkmann, 2010; Dai et al, 2013; Shahmoradian et al, 2013; Tsai et al, 2014; Darrow et al, 2015) or for quantification (Rigort et al, 2012; Rusu et al, 2012). To date, most cryoET studies involving intact mammalian cells have focused on annotating a single (or in some cases a few) macromolecular complex(es) (Koning et al, 2008; Maurer et al, 2008; Patla et al, 2010; Ibiricu et al, 2011; Gilliam et al, 2012; Shahmoradian et al, 2014; Woodward et al, 2014; Page et al, 2015; Wang et al, 2015). …”

A validated active contour method driven by parabolic arc model for detection and segmentation of mitochondria

“…We additionally tested our algorithm on a cryotomography (cryoET) dataset (ID: 6471) in EMDataBank (Wang et al, 2015). This dataset is quite large and has very low SNR.…”

Cellular structural biology as revealed by cryo-electron tomography

“…Based on their analysis, the team designed a predictive model, where malignancy was predicted solely by analyzing the number of mitochondria and the microtubule length in platelets. Malignancy was correctly assigned in 20 of 23 cases (87%), indicating that the ultrastructure of platelets could be a valuable tool, in the future, for detecting ovarian cancer (Wang et al, 2015).…”

“…Recently, Wang et al have illustrated how cryo-ET can be utilized as a noninvasive method to detect structural biomarkers of diseases that affect platelets (Wang et al, 2015). For example, it is known that the count and functionality of platelets can be altered in cancer patients.…”