Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray

Abstract

Background: The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.Methods: Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n ¼ 210) and validation-2 (n ¼ 113)] using a high-density reverse-phase protein microarray.Results: From a total of 53,009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann-Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae.Conclusions: Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer.Impact: The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies. Cancer Epidemiol Biomarkers Prev; 20(10); 2195-203. Ó2011 AACR.

Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics

“…Plasma samples for RPPAs (set for RPPAs) and LC-MS/MS analysis (early-stage set and all-stage set) listed in Table 1 were collected from seven medical institutions as part of the “Third-Term Comprehensive Control Research for Cancer” project and stored at -80°C at the National Cancer Center Research Institute until analysis as described previously [17,18,28]. All study subjects were finally diagnosed and classified at each institution before RPPA and LC-MS/MS analysis were performed.…”

Adipophilin as prognostic biomarker in clear cell renal cell carcinoma

“…Adipophilin is one of the important players in lipid metabolism, responsible for storage of lipid droplets in all types of cells [4, 5]. Some recent studies show that many tumors overexpress adipophilin [6–22], especially those with clear cell histology [10, 11]. Several small reports showed that renal cell carcinoma (RCC) cells also overexpress adipophilin [10, 11, 23–27] and one major study [24] reported the prognostic role of this biomarker in clear cell subtype on transcript level.…”

PLIN2 confers gefitinib resistance by inhibiting cell apoptosis via activation of EGFR/AKT/survivin in PC9R cells

“…Lung tumours exhibit abnormalities in vessels structure that limit the supply of nutrients and leads to hypoxia; therefore, metabolic processes such as carbohydrate and lipid metabolism must be altered in order to support cell growth [17]. Indeed, lipid metabolism has been implicated in lung cancer progression [18], while other studies have reported that PLIN2 is overexpressed in breast and colorectal cancers and malignant melanoma [9][10] and promoted ccRCC proliferation by inhibiting ER stress through increased lipid storage [11]. PLIN2 expression in a subset of lung adenocarcinoma cases is associated with the presence of wild-type EGFR and reduced overall survival [12].…”

“…PLIN1 is primarily expressed in adipose and steroidogenic cells, while PLIN2 is ubiquitously expressed and functions as the predominant LD coat protein in non-adipose tissues [8], playing a key role in fatty acid uptake, LD formation, and lipid storage. Previous studies have shown that PLIN2 is upregulated in many cancers, including clear cell renal cell carcinoma (ccRCC), malignant melanoma, and colorectal cancer [9][10]. Hypoxia-inducible factor (HIF)-2α was found to promote PLIN2 expression and lipid storage in ccRCC cell lines, which was required for endoplasmic reticulum (ER) homeostasis and resistance to cytotoxic ER stress [11].…”