Detection and localization of early- and late-stage cancers using platelet RNA

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

The role of blood platelets in tumor angiogenesis

AbstractCoagulation abnormalities occur frequently in cancer patients. It is becoming evident that blood platelets have an important function in this process. However, understanding of the underlying mechanisms is still very modest. In this review, we discuss the role of platelets in tumor angiogenesis and growth and suggest their potential significance in malignancies. Platelets contain various pro-and antiangiogenic molecules, which seem to be endocytosed and sequestered in different populations of α-granules. Furthermore, tumor endothelial cells are phenotypically and functionally different from endothelial cells in healthy tissue, stimulating local platelet adhesion and subsequent activation. As a consequence, platelets are able to secrete their angiogenic and angiostatic content, most likely in a regulated manner. The overall effect of these platelet–endothelium interactions appears to be proangiogenic, stimulating tumor angiogenesis. We favor the view that local adhesion and activation of blood platelets and dysregulation of coagulation represent underestimated pathways in the progression of cancer

Platelets as messengers of early-stage cancer

Platelets have an important role in tumor angiogenesis, growth, and metastasis. The reciprocal interaction between cancer and platelets results in changes of several platelet characteristics. It is becoming clear that analysis of these platelet features could offer a new strategy in the search for biomarkers of cancer. Here, we review the human studies in which platelet characteristics (e.g., count, volume, protein, and mRNA content) are investigated in early-stage cancer. The main focus of this paper is to evaluate which platelet features are suitable for the development of a blood test that could detect cancer in its early stages

Human splanchnic amino-acid metabolism

Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (−36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (−58.0 ± 4.4 µmol/L and −61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (−12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (−9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine–citrulline pathway appears to be functional in the small intestine but not in the colon

Quantitative and qualitative changes in platelet traits of sunitinib-treated patients with renal cell carcinoma in relation to circulating sunitinib levels: a proof-of-concept study

Background Tyrosine kinase inhibitors (TKIs), such as sunitinib, are used for cancer treatment, but may also affect platelet count and function with possible hemostatic consequences. Here, we investigated whether patient treatment with the TKI sunitinib affected quantitative and qualitative platelet traits as a function of the sunitinib level and the occurrence of bleeding. Methods Blood was collected from 20 metastatic renal cell carcinoma (mRCC) patients before treatment, and at 2 weeks, 4 weeks and 3 months after sunitinib administration. We measured blood cell counts, platelet aggregation, and concentrations of sunitinib as well as its N-desethyl metabolite in plasma, serum and isolated platelets. Progression of disease (PD) and bleeding were monitored after 3 months. Results In sunitinib-treated mRCC patients, concentrations of (N-desethyl-)sunitinib in plasma and serum were highly correlated. In the patients' platelets the active metabolite levels were relatively increased as compared to sunitinib. On average, a sustained reduction in platelet count was observed on-treatment, which was significantly related to the inhibitor levels in plasma/serum. Principal component and correlational analysis showed that the (N-desethyl-)sunitinib levels in plasma/serum were linked to a reduction in both platelet count and collagen-induced platelet aggregation. The reduced aggregation associated in part with reported bleeding, but did not correlate to PD. Conclusion The sunitinib-induced reduction in quantitative and qualitative platelet traits may reflect the effective sunitinib levels in the patient. These novel results may serve as a proof-of-principle for other TKI-related drugs, where both platelet count and functions are affected, which could be used for therapeutic drug monitoring