| 1. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 2. |
- Best, Myron G., et al.
(författare)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 3. |
- Olsson, Pär A T, 1981-, et al.
(författare)
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All-atomic and coarse-grained molecular dynamics investigation of deformation in semi-crystalline lamellar polyethylene
- 2018
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Ingår i: Polymer. - : Elsevier Ltd. - 0032-3861 .- 1873-2291. ; 153, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- In the present work we have performed classical molecular dynamics modelling to investigate the effects of different types of force-fields on the stress-strain and yielding behaviours in semi-crystalline lamellar stacked linear polyethylene. To this end, specifically the all-atomic optimized potential for liquid simulations (OPLS-AA) and the coarse-grained united-atom (UA) force-fields are used to simulate the yielding and tensile behaviour for the lamellar separation mode. Despite that the considered samples and their topologies are identical for both approaches, the results show that they predict widely different stress-strain and yielding behaviours. For all UA simulations we obtain oscillating stress-strain curves accompanied by repetitive chain transport to the amorphous region, along with substantial chain slip and crystal reorientation. For the OPLS-AA modelling primarily cavitation formation is observed, with small amounts of chain slip to reorient the crystal such that the chains align in the tensile direction. This force-field dependence is rooted in the lack of explicit H-H and C-H repulsion in the UA approach, which gives rise to underestimated ideal critical resolved shear stress. The computed critical resolved shear stress for the OPLS-AA approach is in good agreement with density functional theory calculations and the yielding mechanisms resemble those of the lamellar separation mode. The disparate energy and shear stress barriers for chain slip of the different models can be interpreted as differently predicted intrinsic activation rates for the mechanism, which ultimately are responsible for the observed diverse responses of the two modelling approaches. © 2018 Elsevier Ltd
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| 4. |
- Sol, Nik, et al.
(författare)
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Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
- 2020
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Ingår i: Cell Reports Medicine. - : Elsevier. - 2666-3791. ; 1:7
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.
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