title: Gprc5a-knockout mouse lung epithelial cells predicts ceruloplasmin, lipocalin 2 and periostin as potential biomarkers at early stages of lung tumorigenesis.
abstract: Lung cancer is the leading cause of cancer death. As most of lung cancer patients were diagnosed with the advanced stage, early detection is considered as the most effective strategy to reduce high mortality. Thus, it is desirable to identify specific biomarkers at early stages of lung tumorigenesis. GPRC5A is a lung tumor suppressor gene. GPRC5A deficiency is linked to lung cancer development. We hyposthesized that, dysregulated gene expression that results from Gprc5a deficiency may provide potential biomarkers at early stages of lung tumorigenesis. By analysis of top 20 upregulated genes in mouse tracheal epithelial cells (MTEC) of Gprc5a knockout (KO) vs wild-type (WT), we found that ceruloplasmin, lipocalin-2, and periostin are not only upregulated in lung epithelial cells of Gprc5a-ko mice, but also expressed at high levels in lung tumor tissues of Gprc5a-ko mice. This suggests that increased expression of these genes is associated with lung tumorigenesis. Importantly, expression of ceruloplasmin, lipocalin-2, and periostin has also been found to be significantly increased, both at mRNA and protein levels, in the lung tissues from NSCLC patients, which is correlated with repressed GPRC5A. Thus, dysregulated ceruloplasmin, lipocalin-2, and periostin may be used as potential biomarkers at early stages of lung tumorigenesis.
authors.affiliation: Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Guo
authors.affiliation: Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Song
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Biobank, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Keke
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Biobank, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xing
authors.affiliation: Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.|Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Baohui
authors.initials: B
authors.lastname: Han
authors.affiliation: Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Deng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002570:Ceruloplasmin / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D000071068:Lipocalin-2 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C116760:GPRC5A protein, human; C554251:GPRC5A protein, mouse; D000071068:Lipocalin-2; C082838:Postn protein, mouse; D043562:Receptors, G-Protein-Coupled; D002570:Ceruloplasmin
keywords: Gprc5a; biomarker; ceruloplasmin; lung cancer