title: LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma.
abstract: Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide. We investigated the differential expression and putative tumor biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e., LGR4, LGR6, GPR34, GPR160, and GPR171. Based on our previous microarray analyses, we identified five candidate genes in human GC samples. Real-time RT-PCR was carried out to validate their expression in malignant and non-malignant tissues on an independent collective comprising 32 GC patients with and without lymph node metastases. Selected protein targets LGR4 and LGR6 were further validated on paraffin-embedded sections of ten intestinal and ten poorly cohesive (diffuse)-type GCs and their corresponding non-malignant tissue using immunohistochemistry. Additionally, the putative tumor biological significance of LGR4 and LGR6 was studied using tissue microarrays obtained from a cohort of 481 GC patients. On transcriptional level, GPR34, GPR160, and GPR171 were not differentially expressed in GC compared with non-neoplastic mucosa. LGR4 and LGR6 were up-regulated on transcriptional (real-time RT-PCR) and translational (immunohistochemistry) levels in GC. Furthermore, in tissue microarray analysis, LGR6 expression was significantly associated with local tumor growth (T-category; p = 0.04) and correlated with patient survival. LGR4 expression was significantly correlated with nodal spread (N-category; p = 0.025). Our systematic analysis indicates that LGR4 and LGR6 may play a role in GC biology. Future studies will have to demonstrate whether these are also putative diagnostic, prognostic, and/or therapeutic targets for GC.
authors.affiliation: Institute of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Jan Simon
authors.initials: JS
authors.lastname: Steffen
authors.forename: Eva
authors.initials: E
authors.lastname: Simon
authors.forename: Viktoria
authors.initials: V
authors.lastname: Warneke
authors.forename: Katharina
authors.initials: K
authors.lastname: Balschun
authors.forename: Matthias
authors.initials: M
authors.lastname: Ebert
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D049312:Receptors, Lysophospholipid / Q000378:metabolism; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C118065:G-protein-coupled receptor 34; C555417:GPR160 protein, human; C411562:LGR4 protein, human; C417544:LGR6 protein, human; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid