title: High expression of GPER1, EGFR and CXCR1 is associated with lymph node metastasis in papillary thyroid carcinoma.
abstract: Clinical and epidemiological studies have shown that estrogen may be involved in the development and progression of papillary thyroid carcinoma (PTC). G protein-coupled estrogen receptor 1 (GPER1) is a novel seven-transmembrane estrogen receptor that functions alongside traditional nuclear estrogen receptors (ERs) to regulate the cellular responses to estrogen. The purpose of this study was to examine GPER1, EGFR and CXCR1 expression in PTC and to assess the association of their expression with clinicopathological indicators. GPER1, EGFR and CXCR1 protein expression in 129 PTCs, 61 nodular hyperplasia and 118 normal thyroid tissue specimens were analyzed using immunohistochemistry. The protein expression levels of these three molecules were up-regulated in PTCs. High protein expression of GPER1, EGFR and CXCR1 was significantly correlated with lymph node metastasis (LNM) (P ≤ 0.001). Furthermore, GPER1, EGFR and CXCR1 protein expression were correlated with one another. Concomitant high expression of these molecules had stronger correlation with LNM than did each alone (P = 0.002 for GPER1/EGFR, P = 0.013 for GPER1/CXCR1, P = 0.018 for EGFR/CXCR1 and P < 0.001 for GPER1/EGFR/CXCR1). Additionally, GPER1, EGFR and CXCR1 mRNA expression was assessed in 30 PTCs, 10 nodular hyperplasia and 10 normal thyroid tissue specimens using real-time RT-PCR. GPER1, EGFR and CXCR1 mRNA expression levels were up-regulated in PTCs, and high mRNA expression of GPER1, EGFR and CXCR1 was significantly correlated with LNM (P < 0.001 for all these three molecules). These results demonstrated that the evaluation of GPER1, EGFR and CXCR1 expression in PTC may be useful in predicting the risk of LNM.
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University Chongqing, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University Chongqing, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University Chongqing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital Shatin, N.T., Hong Kong, China.
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Chongqing Medical University Chongqing, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Liu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000473:pathology*; D002291:Carcinoma, Papillary; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000096:biosynthesis*; D023062:Receptors, Interleukin-8A / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000473:pathology*; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D023062:Receptors, Interleukin-8A; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: CXCR1; EGFR; GPER1; papillary thyroid carcinoma