Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer

Kulasingam, Vathany; Pavlou, Maria; Diamandis, Eleftherios P.

doi:10.1038/nrc2831

Cited by 136 publications

(116 citation statements)

References 56 publications

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“…The fact that our SRM assays failed to quantify 12 of the 40 proteins we targeted might be related to the detection limit we set for low-abundance proteins in our unfractionated, complex samples (54,55), because it was higher than that used for fractionated peptide digests in our previous study (34). It is also possible that the endogenous proteotypic peptides we selected to represent these proteins had suboptimal MS signal responses.…”

Section: Figmentioning

confidence: 76%

Targeted Proteomics for Multiplexed Verification of Markers of Colorectal Tumorigenesis

Uzozie

Selevsek

Wåhlander

et al. 2017

Molecular & Cellular Proteomics

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Targeted proteomic methods can accelerate the verification of multiple tumor marker candidates in large series of patient samples. We utilized the targeted approach known as selected/multiple reaction monitoring (S/MRM) to verify potential protein markers of colorectal adenoma identified by our group in previous transcriptomic and quantitative shotgun proteomic studies of a large cohort of precancerous colorectal lesions. We developed SRM assays to reproducibly detect and quantify 25 (62.5%) of the 40 selected proteins in an independent series of precancerous and cancerous tissue samples (19 adenoma/ normal mucosa pairs; 17 adenocarcinoma/normal mucosa pairs). Twenty-three proteins were significantly upregulated (n ‫؍‬ 17) or downregulated (n ‫؍‬ 6) in adenomas and/or adenocarcinomas, as compared with normal mucosa (linear fold changes > ؎1.3, adjusted p value <0.05). Most changes were observed in both tumor types (up-regulation of ANP32A, ANXA3, SORD, LDHA, LCN2, NCL, S100A11, SERPINB5, CDV3, OLFM4, and REG4; downregulation of ARF6 and PGM5), and a fiveprotein biomarker signature distinguished neoplastic tissue from normal mucosa with a maximum area under the receiver operating curve greater than 0.83. Other changes were specific for adenomas (PPA1 and PPA2 up-regulation; KCTD12 downregulation) or adenocarcinoma (ANP32B, G6PD, RCN1, and SET up-regulation; downregulated AKR1B1, APEX1, and PPA1). Some changes significantly correlated with a few patient-or tumor-related phenotypes. Twenty-two (96%) of the 23 proteins have a potential to be released from the tumors into the bloodstream, and their detectability in plasma has been previously reported. The proteins identified in this study expand the pool of biomarker candidates that can be used to develop a standardized precolonoscopy blood test for the early detection of colorectal tumors. Molecular & Cellular

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Section: Figmentioning

confidence: 76%

Targeted Proteomics for Multiplexed Verification of Markers of Colorectal Tumorigenesis

Uzozie

Selevsek

Wåhlander

et al. 2017

Molecular & Cellular Proteomics

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“…The integration of pancreatic specific proteomic data and bioinformatic data mining is a reasonable way to derive highly promising biomarker candidates from thousands of proteins. In our previous publications, we used similar filtering criteria and successfully verified/validated some candidates (17,18). The serological validation of all 16 short-listed candidates (Table II) depends on ELISA assay availability; we have verified our top four candidates: (1) desmoplakin (DSP), (2) laminin, gamma C2 (LAMC2), (3) Golgi membrane protein-1 (GP73), and (4) desmoglein-2 (DSG2).…”

Section: Discussionmentioning

confidence: 99%

Laminin, gamma 2 (LAMC2): A Promising New Putative Pancreatic Cancer Biomarker Identified by Proteomic Analysis of Pancreatic Adenocarcinoma Tissues

Kosanam

Prassas

Chrystoja

et al. 2013

Molecular & Cellular Proteomics

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101

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In pancreatic cancer, the incidence and mortality curves coincide. One major reason for this high mortality rate in pancreatic ductal adenocarcinoma (PDAC) patients is the dearth of effective diagnostic, prognostic, and diseasemonitoring biomarkers. Unfortunately, existing tumor markers, as well as current imaging modalities, are not sufficiently sensitive and/or specific for early-stage diagnosis. There is, therefore, an urgent need for improved serum markers of the disease. Herein, we performed Orbitrap® mass spectrometry proteomic analysis of four PDAC tissues and their adjacent benign tissues and identified a total of 2190 nonredundant proteins. Sixteen promising candidates were selected for further scrutiny using a systematic scoring algorithm. Our preliminary serum verification of the top four candidates (DSP, LAMC2, GP73, and DSG2) in 20 patients diagnosed with pancreatic cancer and 20 with benign pancreatic cysts, showed a significant (p < 0.05) elevation of LAMC2 in pancreatic cancer serum. Extensive validation of LAMC2 in healthy, benign, and PDAC sera from geographically diverse cohorts (n ‫؍‬ 425) (Japan, Europe, and USA) demonstrated a significant increase in levels in early-stage PDAC compared with benign diseases. The sensitivity of LAMC2 was comparable to CA19.9 in all data sets, with an AUC value greater than 0.85 in discriminating healthy patients from early-stage PDAC patients. LAMC2 exhibited diagnostic complementarity with CA19.9 by showing significant (p < 0.001 in two out of three cohorts) elevation in PDAC patients with clinically low CA19.9 levels. Molecular & Cellular

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“…More recently, we opened up new areas based on our core competencies in quantitative analytical chemistry. We apply mass spectrometry-based proteomic approaches for novel biomarker identification (6,7 ). These programs are flourishing with both industrial as well as other funding, because they are attempting to address a very clearly defined clinical need.…”

Section: Eleftherios P Diamandismentioning

confidence: 99%

Advancing Laboratory Medicine through Innovation: A Tale of Six Inventors

Rifai

Diamandis

et al. 2012

Clinical Chemistry

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Integrating high-throughput technologies in the quest for effective biomarkers for ovarian cancer

Cited by 136 publications

References 56 publications

Targeted Proteomics for Multiplexed Verification of Markers of Colorectal Tumorigenesis

Targeted Proteomics for Multiplexed Verification of Markers of Colorectal Tumorigenesis

Laminin, gamma 2 (LAMC2): A Promising New Putative Pancreatic Cancer Biomarker Identified by Proteomic Analysis of Pancreatic Adenocarcinoma Tissues

Advancing Laboratory Medicine through Innovation: A Tale of Six Inventors

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