Secretomes are a potential source of molecular targets for cancer therapies and indicate that APOE is a candidate biomarker for lung adenocarcinoma metastasis

Identifying patients at high risk of metastasis is a major challenge in lung adenocarcinoma (ADC) therapy, therefore discovery of noninvasive biomarkers and therapeutic targets is urgent. We found significant differences between the secretomes of differentially expressed proteins in lung ADC cell lines, clinical tissue samples and serum plasma samples with high and low metastatic potential. In particular, Apolipoprotein E (APOE) levels were three-times greater in cells with lymph node metastases (LNM) than those without. Our study indicates that APOE is a potential indicator of metastatic lung ADC and that secretomes may offer a valuable resource for biomarkers of lung ADC with LNM.

[1]  K. Waltner,et al.  Effects of metal salts on the electrolyte content of human red blood cells. , 1960, Clinica chimica acta; international journal of clinical chemistry.

[2]  J. Folkman.  Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[3]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[4]  R. Mahley,et al.  Apolipoprotein E: far more than a lipid transport protein. , 2000, Annual review of genomics and human genetics.

[5]  S. Bron,et al.  Signal Peptide-Dependent Protein Transport inBacillus subtilis: a Genome-Based Survey of the Secretome , 2000, Microbiology and Molecular Biology Reviews.

[6]  Y. Mitani,et al.  Gene Expression Profile of Gastric Carcinoma , 2004, Cancer Research.

[7]  W. Schmiegel,et al.  Differential proteome analysis of conditioned media to detect Smad4 regulated secreted biomarkers in colon cancer , 2005, Proteomics.

[8]  Sean L Seymour,et al.  The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra*S , 2007, Molecular & Cellular Proteomics.

[9]  L. Holmberg,et al.  Lung cancer incidence in never smokers. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  D. Lin,et al.  Cathepsin D is secreted from M-BE cells: its potential role as a biomarker of lung cancer. , 2007, Journal of proteome research.

[11]  Chun-Ming Huang,et al.  Breast tumor microenvironment: proteomics highlights the treatments targeting secretome. , 2008, Journal of proteome research.

[12]  S. Hanash,et al.  Mining the plasma proteome for cancer biomarkers , 2008, Nature.

[13]  K. Mimori,et al.  Clinical significance of ApoE expression in human gastric cancer. , 2008, Oncology reports.

[14]  M. Lai,et al.  The cancer secretome: a reservoir of biomarkers , 2008, Journal of Translational Medicine.

[15]  Bor-Sen Chen,et al.  Global screening of potential Candida albicans biofilm-related transcription factors via network comparison , 2010, BMC Bioinformatics.

[16]  C. Greenwood,et al.  Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer , 2009, British Journal of Cancer.

[17]  N. Rothman,et al.  Apolipoprotein E/C1 locus variants modify renal cell carcinoma risk. , 2009, Cancer research.

[18]  E. Diamandis,et al.  Identification of Five Candidate Lung Cancer Biomarkers by Proteomics Analysis of Conditioned Media of Four Lung Cancer Cell Lines* , 2009, Molecular & Cellular Proteomics.

[19]  D. Tai,et al.  Candidate Serological Biomarkers for Cancer Identified from the Secretomes of 23 Cancer Cell Lines and the Human Protein Atlas* , 2010, Molecular & Cellular Proteomics.

[20]  A. Skubitz,et al.  Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum , 2010, Proteome Science.

[21]  M. Lai,et al.  Identification of serum biomarkers for colorectal cancer metastasis using a differential secretome approach. , 2010, Journal of proteome research.

[22]  Mehmet Koyutürk,et al.  An Integrative -omics Approach to Identify Functional Sub-Networks in Human Colorectal Cancer , 2010, PLoS Comput. Biol..

[23]  Roded Sharan,et al.  Associating Genes and Protein Complexes with Disease via Network Propagation , 2010, PLoS Comput. Biol..

[24]  Yu-Chao Wang,et al.  A network-based biomarker approach for molecular investigation and diagnosis of lung cancer , 2011, BMC Medical Genomics.

[25]  A. Vlahou,et al.  Secretome proteomics for discovery of cancer biomarkers. , 2010, Journal of proteomics.

[26]  W. Su,et al.  Apolipoprotein E expression promotes lung adenocarcinoma proliferation and migration and as a potential survival marker in lung cancer. , 2011, Lung cancer.

[27]  Yusuke Nakamura,et al.  A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma , 2011, PloS one.

[28]  V. Kuznetsov,et al.  A robust tool for discriminative analysis and feature selection in paired samples impacts the identification of the genes essential for reprogramming lung tissue to adenocarcinoma , 2011, BMC Genomics.

[29]  A. Yashin,et al.  Trade‐off in the effects of the apolipoprotein E polymorphism on the ages at onset of CVD and cancer influences human lifespan , 2011, Aging cell.

[30]  Hwee Tong Tan,et al.  Mining the gastric cancer secretome: identification of GRN as a potential diagnostic marker for early gastric cancer. , 2012, Journal of proteome research.

[31]  M. Saadat.  Apolipoprotein E (APOE) Polymorphisms and Susceptibility to Breast Cancer: A Meta-Analysis , 2012, Cancer research and treatment : official journal of Korean Cancer Association.

[32]  S. Goodison,et al.  A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer , 2012, PloS one.

[33]  J. V. Van Eyk,et al.  Secreted proteins as a fundamental source for biomarker discovery , 2012, Proteomics.

[34]  Yaoh-Shiang Lin,et al.  Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade , 2013, PloS one.

[35]  Yumin Wang,et al.  The diagnostic value of apolipoprotein E in malignant pleural effusion associated with non-small cell lung cancer. , 2013, Clinica chimica acta; international journal of clinical chemistry.

[36]  Herbert Y. Lin,et al.  A novel validated enzyme-linked immunosorbent assay to quantify soluble hemojuvelin in mouse serum , 2013, Haematologica.

[37]  G. Colditz,et al.  Online Continuing Education Activity Article Title: American Cancer Society Lung Cancer Screening Guidelines Continuing Medical Education Accreditation and Designation Statement: Continuing Nursing Education Accreditation and Designation Statement: Educational Objectives: Activity Disclosures Acs Co , 2022 .

[38]  Jiong Chen,et al.  Expression and clinical significance of complement C3, complement C4b1 and apolipoprotein E in pancreatic cancer , 2013, Oncology letters.

[39]  A. Hotz-Wagenblatt,et al.  In-depth mass spectrometric mapping of the human vitreous proteome , 2013, Proteome Science.