Repositorio
Institucional

Marimuthu, Arivusudar

Subbannayya, Yashwanth

Sahasrabuddhe, Nandini A.

Balakrishnan, Lavanya

Syed, Nazia

Sekhar, Nirujogi Raja

Katte, Teesta V.

Pinto, Sneha M.

Srikanth, Srinivas M.

Kumar, Praveen

Pawar, Harsh

Kashyap, Manoj K.

Maharudraiah, Jagadeesha

Ashktorab, Hassan

Smoot, Duane T.

Ramaswamy, Girija

Kumar, Rekha V.

Cheng, Yulan

Meltzer, Stephen J.

Carlos Roa, Juan

Chaerkady, Raghothama

Prasad, T. S. Keshava

Harsha, H. C.

Chatterjee, Aditi

Pandey, Akhilesh

SILAC-based quantitative proteomic analysis of gastric cancer secretome

WILEY-V C H VERLAG GMBH

PROTEOMICS CLINICAL APPLICATIONS

en

Purpose Gastric cancer is a commonly occurring cancer in Asia and one of the leading causes of cancer deaths. However, there is no reliable blood-based screening test for this cancer. Identifying proteins secreted from tumor cells could lead to the discovery of clinically useful biomarkers for early detection of gastric cancer. Experimental design A SILAC-based quantitative proteomic approach was employed to identify secreted proteins that were differentially expressed between neoplastic and non-neoplastic gastric epithelial cells. Proteins from the secretome were subjected to SDS-PAGE and SCX-based fractionation, followed by mass spectrometric analysis on an LTQ-Orbitrap Velos mass spectrometer. Immunohistochemical labeling was employed to validate a subset of candidates using tissue microarrays. Results We identified 2205 proteins in the gastric cancer secretome of which 263 proteins were overexpressed greater than fourfold in gastric cancer-derived cell lines as compared to non-neoplastic gastric epithelial cells. Three candidate proteins, proprotein convertase subtilisin/kexin type 9 (PCSK9), lectin mannose binding 2 (LMAN2), and PDGFA-associated protein 1 (PDAP1) were validated by immunohistochemical labeling. Conclusions and clinical relevance We report here the largest cancer secretome described to date. The novel biomarkers identified in the current study are excellent candidates for further testing as early detection biomarkers for gastric adenocarcinoma.

Artículo original

We thank the Department of Biotechnology (DBT) of the Government of India for research support to the Institute of Bioinformatics, Bangalore, India. NAS, HP, NRS, and SMP are recipients of Senior Research fellowships from the Council of Scientific and Industrial Research (CSIR), India. YS, SMS, and NS are recipients of research fellowships from the University Grants Commission (UGC). T. S. Keshava Prasad is supported by a research grant on "Development of Infrastructure and a Computational Framework for Analysis of Proteomic Data" from DBT. Harsha Gowda is a Wellcome Trust/DBT India Alliance Early Career fellow. We thank Dr. S.K. Shankar and Dr. Anita Mahedavan for providing access to the microscopic facility. This study was supported in part by NIH grants U24CA160036 and G12 MD007597.

Agradecemos al Departamento de Biotecnología (DBT) del Gobierno de la India por el apoyo a la investigación brindado al Instituto de Bioinformática de Bangalore, India. NAS, HP, NRS y SMP son beneficiarios de becas de investigación sénior del Consejo de Investigación Científica e Industrial (CSIR) de la India. YS, SMS y NS son beneficiarios de becas de investigación de la Comisión de Subvenciones Universitarias (UGC). T. S. Keshava Prasad cuenta con el apoyo de una beca de investigación del DBT sobre "Desarrollo de infraestructura y un marco computacional para el análisis de datos proteómicos". Harsha Gowda es becario de la Alianza Wellcome Trust/DBT India para jóvenes investigadores. Agradecemos al Dr. S.K. Shankar y a la Dra. Anita Mahedavan por facilitar el acceso a las instalaciones de microscopía. Este estudio fue financiado en parte por las subvenciones U24CA160036 y G12 MD007597 de los NIH.

10.1002/prca.201200069

pdf

Biomarkers

Cell supernatants

Early diagnosis

Gastric carcinoma

In vivo labeling

Secreted proteins

SQUAMOUS-CELL CARCINOMA

FOLLISTATIN-LIKE 1

PROPROTEIN CONVERTASES

BINDING-PROTEIN

EXPRESSION

IDENTIFICATION

TISSUE

INVASIVENESS

LECTINS

GROWTH

Biomarcadores

Sobrenadantes celulares

Diagnóstico precoz

Carcinoma gástrico

Marcaje in vivo

Proteínas secretadas

CARCINOMA DE CÉLULAS ESCAMOSAS

FOLLISTATINA-LIKE 1

PROPROTEÍNA CONVERTASAS

PROTEÍNA DE UNIÓN

EXPRESIÓN

IDENTIFICACIÓN

TEJIDO

INVASIVIDAD

LECTINAS

CRECIMIENTO

Biomarkers

Cell supernatants

Early diagnosis

Gastric carcinoma

In vivo labeling

Secreted proteins

SQUAMOUS-CELL CARCINOMA

FOLLISTATIN-LIKE 1

PROPROTEIN CONVERTASES

BINDING-PROTEIN

EXPRESSION

IDENTIFICATION

TISSUE

INVASIVENESS

LECTINS

GROWTH

Biomarcadores

Sobrenadantes celulares

Diagnóstico precoz

Carcinoma gástrico

Marcaje in vivo

Proteínas secretadas

CARCINOMA DE CÉLULAS ESCAMOSAS

FOLLISTATINA-LIKE 1

PROPROTEÍNA CONVERTASAS

PROTEÍNA DE UNIÓN

EXPRESIÓN

IDENTIFICACIÓN

TEJIDO

INVASIVIDAD

LECTINAS

CRECIMIENTO

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Oncología

SILAC-based quantitative proteomic analysis of gastric cancer secretome

PROTEOMICS CLINICAL APPLICATIONS

hibrida

metadata

metadata

PMID 23161554

en

Artículo original

versión publicada

Department of Biotechnology (DBT) of the Government of India#Council of Scientific and Industrial Research (CSIR), India#University Grants Commission (UGC)#DBT#NIH U24CA160036#NIH G12 MD007597

Department of Biotechnology (DBT) of the Government of India

Council of Scientific and Industrial Research (CSIR), India

University Grants Commission (UGC)

DBT

NIH U24CA160036

NIH G12 MD007597

WILEY-V C H VERLAG GMBH

1862-8346

355

366

Métodos de investigación bioquímica

Bioquímica y biología molecular

Biochemical Research Methods

Biochemistry & Molecular Biology

pdf

WOS:000320554800005