RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

被引：805

作者：

Best, Myron G. ^{[1
,2
]}

Sol, Nik ^{[3
]}

Kooi, Irsan ^{[4
]}

Tannous, Jihane ^{[5
,6
]}

Westerman, Bart A. ^{[2
]}

Rustenburg, Francois ^{[1
,2
]}

Schellen, Pepijn ^{[2
,7
]}

Verschueren, Heleen ^{[2
,7
]}

Post, Edward ^{[2
,7
]}

Koster, Jan ^{[8
]}

Ylstra, Bauke ^{[1
]}

Ameziane, Najim ^{[4
]}

Dorsman, Josephine ^{[4
]}

Smit, Egbert F. ^{[9
]}

Verheul, Henk M. ^{[10
]}

Noske, David P. ^{[2
]}

Reijneveld, Jaap C. ^{[3
]}

Nilsson, R. Jonas A. ^{[2
,7
,11
]}

Tannous, Bakhos A. ^{[5
,6
]}

Wesseling, Pieter ^{[1
,12
]}

Wurdinger, Thomas ^{[2
,5
,6
,7
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pathol, NL-1081 HV Amsterdam, Netherlands

[2] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands

[3] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurol, NL-1081 HV Amsterdam, Netherlands

[4] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands

[5] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA

[6] Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA

[7] thromboDx BV, NL-1098 EA Amsterdam, Netherlands

[8] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands

[9] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pulm Dis, NL-1081 HV Amsterdam, Netherlands

[10] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands

[11] Umea Univ, Dept Radiat Sci, S-90185 Umea, Sweden

[12] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands

来源：

CANCER CELL | 2015年 / 28卷 / 05期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

GENE-EXPRESSION SIGNATURES; METASTATIC BREAST-CANCER; MESSENGER-RNA; LUNG-CANCER; TRANSCRIPTIONAL LANDSCAPE; CLINICAL VALIDATION; ANUCLEATE PLATELETS; ACTIVATED PLATELETS; CLASS PREDICTION; PLASMA DNA;

D O I：

10.1016/j.ccell.2015.09.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".

引用

页码：666 / 676

页数：11

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