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Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets

A cancer, lung cancer technology, applied in the field of medical diagnosis, disease diagnosis and monitoring

Inactive Publication Date: 2019-04-16
スティッチングヴィユーエムシー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A well-known challenge lies in the identification of optimal biomarker panels from such liquid biosources

Method used

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  • Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets
  • Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets
  • Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets

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Experimental program
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Embodiment 1

[0209] General Materials and Methods

[0210] Study Design and Sample Selection

[0211] At VU University Medical Center, Amsterdam, The Netherlands, Netherlands Cancer Institute (NKI / AvL), Amsterdam, The Netherlands, Academy Medical Center, Amsterdam, The Netherlands, Utrecht Medical Center, Utrecht, The Netherlands, Umea, Umea, Sweden University Hospital, the Hospital GermansTrias iPujol in Barcelona, ​​Spain, the University Hospital of Pisa in Pisa, Italy, and Massachusetts General Hospital in Boston, USA, from patients with cancer, inflammatory and other Peripheral whole blood was drawn from patients with non-cancerous conditions as well as from asymptomatic individuals. Whole blood was collected in 4, 6, or 10-mL EDTA-coated purple-capped BD Vacutainers containing the anticoagulant EDTA. Patients with cancer were diagnosed clinically, radiologically, and pathologically, and confirmed to have a detectable tumor burden at the time of blood collection. The 106 NSCLC samp...

Embodiment 2

[0263] By analyzing SMARTer-amplified platelet RNA samples, we observed subtle differences in SMARTer cDNA profiles (Fig. 4f), as measured by the Bioanalyzer DNA High Sensitivity Chip. The slopes of cDNA products could be subdivided into protruding, smooth and intermediate-order protruding / smooth profiles and did not tend to be disease specific (Fig. 4g). The most abundantly observed pattern of protrusions of slope (in non-cancer as 59% of the NSCLC cohort) may be related to the relatively small diversity of RNA molecules in platelets (approximately 4000-5000 different RNAs measured). The remaining samples were characterized by smooth or mid-order protruding / smooth cDNA product profiles. Notably, Picochip RNA profiles and DNA7500Truseq cDNA profiles were similar across the three SMARTer groups (Fig. 4f), and none of the SMARTer groups were enriched in low-quality RNA samples. The average cDNA length can be correlated with the SMARTer profile, and the cDNA yield after SMARTer ...

Embodiment 3

[0265]RNA-seq data offer the opportunity to quantify virtually any region of the transcriptome at high resolution. We therefore investigated the distribution of RNA species in the platelet RNA profile. The platelets analyzed in this study constitute a snapshot of all platelets circulating in the blood at the time of blood collection and can be affected by variables such as total platelet count, medications, bleeding disorders, injury, activity or exercise, and circadian rhythms. For the following analyses, to reduce the influence of factors highly suspected of confounding platelet characteristics (Table 4), we selected 263 patients matched for age and blood storage time. Based on intron read count analysis, we identified 1625 spliced ​​platelet genes with significantly differential splicing levels (FDR<0.01, 698 genes with enhanced splicing in platelets from NSCLC patients and 927 genes in platelets from NSCLC patients gene has reduced splicing), consistent with previous find...

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Abstract

The invention provides methods of administering immunotherapy that modulates an interaction between PD-1 and its ligand, to a cancer patient, based on tumor-educated gene expression profiles obtainedfrom anucleated cells. The invention further provides methods of typing a sample of a subject for the presence or absence of a cancer, based on tumor-educated gene expression profiles obtained from anucleated cells. The invention further provides a method for obtaining a biomarker panel for typing of a sample from a subject using particle swarm optimization-based algorithms.

Description

technical field [0001] The invention belongs to the field of medical diagnosis, especially the field of disease diagnosis and monitoring. The present invention relates to markers for detecting diseases, methods for detecting diseases, and methods for determining the efficacy of treatment for diseases. Background technique [0002] Cancer is one of the leading causes of death in developed countries. Research shows that many cancer patients are diagnosed at later stages, which are more difficult to treat. Cancer is primarily driven by sequential mutations in normal cells, resulting in DNA damage and ultimately overt genetic alterations leading to a cancerous state. [0003] Cancer is often diagnosed based on tumor markers. Tumor markers are substances that are present in cancer cells or produced by another cell in response to cancer. Some tumor markers are also present in normal cells, but in cancerous cells, for example, at higher levels in substituted forms. Tumor marke...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/106C12Q2600/158C07K16/2818C07K2317/21
Inventor 托马斯·武丁格尔迈伦·吉斯兰·贝斯特
Owner スティッチングヴィユーエムシー
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