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pmid:28624786
High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma.
Li Yang · Xiao-Lu Lin · Wei Liang · Seng-Wang Fu · Wen-Feng Lin · Xiao-Qing Tian · Yun-Jie Gao · Hao-Yan Chen · Jun Dai · Zhi-Zheng Ge
Oncotarget · 2017 doi:10.18632/oncotarget.18203
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Complete file
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However, the role of GPR116 in colorectal carcinoma (CRC) carcinogenesis and progression is unknown. In this study, We found GPR116 expression was significantly up-regulated in CRC specimens compared with corresponding non-cancerous tissues. Increased GPR116 expression in CRC was correlated with histological differentiation and distant metastasis. In addition, high expression of GPR116 was significantly associated with poor overall survival of CRC patients, which was also confirmed by GSE14333, GSE17536 and GSE33113 datasets from the Gene Expression Omnibus (GEO). Furthermore, we demonstrated that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. 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The dataset of corresponding clinical data used in this study were downloaded from the Gene Expression Omnibus (GEO)."}, {"asset": "source:pmid:28624786", "locator": "sections[6] \"Biological functions of GPR116 in CRC\" paragraph 2", "quote": "Gene set enrichment analysis (GSEA) was performed in The Cancer Genome Atlas (TCGA) datasets to acquire the biologic functions involved in CRC pathogenesis stratified by the median of GPR116 expression level."}, {"asset": "source:pmid:28624786", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "Correlation of GPR116 expression with clinicopathologic factors in patients with CRC was evaluated by Chi-square test. Survival curves were generated using the Kaplan–Meier method. The differences between survival curves were calculated by the Log-rank test. The significant impact of parameters on survival was analyzed by Cox proportional hazards model using univariate and multivariate Cox regression analysis. 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We found that high GPR116 protein expression was obviously associated with reduced overall survival time (p=0, 0.03, and 0.001 respectively, Figure 3B-3D).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM437093", "GSM437094", "GSM437095", "GSM437096", "GSM437097", "GSM437098", "GSM437099", "GSM437100", "GSM437101", "GSM437102", "GSM437103", "GSM437104", "GSM437105", "GSM437106", "GSM437107", "GSM437108", "GSM437109", "GSM437110", "GSM437111", "GSM437112", "GSM437113", "GSM437114", "GSM437115", "GSM437116", "GSM437117", "GSM437118", "GSM437119", "GSM437120", "GSM437121", "GSM437122", "GSM437123", "GSM437124", "GSM437125", "GSM437126", "GSM437127", "GSM437128", "GSM437129", "GSM437130", "GSM437131", "GSM437132", "GSM437133", "GSM437134", "GSM437135", "GSM437136", "GSM437137", "GSM437138", "GSM437139", "GSM437140", "GSM437141", "GSM437142", "GSM437143", "GSM437144", "GSM437145", "GSM437146", "GSM437147", "GSM437148", "GSM437149", "GSM437150", "GSM437151", "GSM437152", "GSM437153", "GSM437154", "GSM437155", "GSM437156", "GSM437157", "GSM437158", "GSM437159", "GSM437160", "GSM437161", "GSM437162", "GSM437163", "GSM437164", "GSM437165", "GSM437166", "GSM437167", "GSM437168", "GSM437169", "GSM437170", "GSM437171", "GSM437172", "GSM437173", "GSM437174", "GSM437175", "GSM437176", "GSM437177", "GSM437178", "GSM437179", "GSM437180", "GSM437181", "GSM437182", "GSM437183", "GSM437184", "GSM437185", "GSM437186", "GSM437187", "GSM437188", "GSM437189", "GSM437190", "GSM437191", "GSM437192", "GSM437193", "GSM437194", "GSM437195", "GSM437196", "GSM437197", "GSM437198", "GSM437199", "GSM437200", "GSM437201", "GSM437202", "GSM437203", "GSM437204", "GSM437205", "GSM437206", "GSM437207", "GSM437208", "GSM437209", "GSM437210", "GSM437211", "GSM437212", "GSM437213", "GSM437214", "GSM437215", "GSM437216", "GSM437217", "GSM437218", "GSM437219", "GSM437220", "GSM437221", "GSM437222", "GSM437223", "GSM437224", "GSM437225", "GSM437226", "GSM437227", "GSM437228", "GSM437229", "GSM437230", "GSM437231", "GSM437232", "GSM437233", "GSM437234", "GSM437235", "GSM437236", "GSM437237", "GSM437238", "GSM437239", "GSM437240", "GSM437241", "GSM437242", "GSM437243", "GSM437244", "GSM437245", "GSM437246", "GSM437247", "GSM437248", "GSM437249", "GSM437250", "GSM437251", "GSM437252", "GSM437253", "GSM437254", "GSM437255", "GSM437256", "GSM437257", "GSM437258", "GSM437259", "GSM437260", "GSM437261", "GSM437262", "GSM437263", "GSM437264", "GSM437265", "GSM437266", "GSM437267", "GSM437268", "GSM437269"], "sample_count": 177, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients (Moffitt Samples)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE33113", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33113", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE33113", "version": null, "note": "To increase the reliability of this result, we obtained the prognostic significance of GPR116 in GSE14333, GSE17536, and GSE33113 with a total of 197, 177, and 89 cases enrolled from the GEO datasets. 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"52", "28 (53.8)", "24 (46.2)", "0.909"], ["Female", "38", "20 (52.6)", "18 (47.4)", ""], ["Tumor location", "", "", "", ""], ["Ascending", "28", "17 (60.7)", "11 (39.3)", "0.522"], ["Transverse", "20", "9 (45.0)", "11 (55.0)", ""], ["Descending", "16", "10 (62.5)", "6 (37.5)", ""], ["Sigmoid", "26", "12 (46.2)", "14 (53.8)", ""], ["TNM stage (AJCC)", "", "", "", ""], ["Stage I", "5", "0 (0.0)", "5 (100.0)", "0.102"], ["Stage II", "37", "20 (54.1)", "17 (45.9)", ""], ["Stage III", "43", "25 (58.1)", "18 (41.9)", ""], ["Stage IV", "5", "3 (60.0)", "2 (40.0)", ""], ["Size", "", "", "", ""], ["<5cm", "34", "16 (47.1)", "18 (52.9)", "0.353"], ["≥5cm", "56", "32 (57.1)", "24 (42.9)", ""], ["Histological differentiation", "", "", "", ""], ["Well/moderate", "56", "25 (45.5)", "31 (54.5)", "0.034"], ["Poor", "34", "23 (65.7)", "11 (34.3)", ""], ["Lymph node metastasis", "", "", "", ""], ["Absent", "46", "22 (47.8)", "24 (52.2)", "0.284"], ["Present", "44", "26 (59.1)", "18 (40.9)", ""], ["Distant metastasis", "", "", "", ""], ["Absent", "85", "43 (50.6)", "42 (49.4)", "0.031"], ["Present", "5", "5 (100.0)", "0 (0.0)", ""]], "row_count": 31, "column_count": 5, "numeric_cells": 77, "header_rows": 2, "locator": "section[4]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:28624786:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:252e01fee8ef0d734c6c11abc495b14492640f8235f8ebe799d21897dc270f7f", "bytes": 1112, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#T2", "version": null, "note": "Univariate and multivariate analysis of prognostic parameters for survival in patients with colorectal carcinoma", "structure": {"pmcid": "PMC5564617", "section_index": 5, "section_title": "Correlation of GPR116 expression with clinicopathological characteristics and prognosis in CRC patients", "row_count": 10, "column_count": 7}, "table": {"label": "Table 2", "caption": "Univariate and multivariate analysis of prognostic parameters for survival in patients with colorectal carcinoma", "rows": [["Prognostic parameter", "Univariate analysis", "Multivariate analysis"], ["HR", "95% CI", "P value", "HR", "95% CI", "P value"], ["Expression of GPR116 (low vs. high)", "2.465", "1.310-4.637", "0.005", "2.693", "1.381-5.255", "0.004"], ["Age (<65 vs. ≥65)", "1.979", "1.025-3.819", "0.042", "2.006", "1.020-3.943", "0.044"], ["Gender (male vs. female)", "0.710", "0.389-1.298", "0.266", "_", "_", "_"], ["Tumor size (<5cm vs. ≥5cm)", "0.842", "0.445-1.596", "0.599", "_", "_", "_"], ["Lymph node metastasis (absent vs. present)", "2.215", "1.192-4.116", "0.012", "1.254", "0.626-2.515", "0.523"], ["Distant metastasis (absent vs. present)", "1.815", "0.711-4.635", "0.213", "_", "_", "_"], ["Tumor location (ascending vs. transverse, descending, sigmoid)", "0.646", "0.340-1.224", "0.180", "_", "_", "_"], ["Histology (well/moderate vs. poor)", "2.080", "1.109-3.903", "0.022", "2.173", "1.036-4.559", "0.040"]], "row_count": 10, "column_count": 7, "numeric_cells": 41, "header_rows": 2, "locator": "section[5]/table-wrap[1]#T2"}}], "gaps": ["asset:data:geo:GSE14333 not downloaded", "asset:data:geo:GSE14333 licence not read", "asset:data:geo:GSE17536 not downloaded", "asset:data:geo:GSE17536 licence not read", "asset:data:geo:GSE33113 not downloaded", "asset:data:geo:GSE33113 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We used the Chi-square test or Fisher's exact test to evaluate the correlation between GPR116 expression and corresponding patients’ clinicopathological parameters."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Log-rank"}}, {"id": "method-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-6", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Fisher's exact"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: chi_square."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14333", "GSE17536", "GSE33113"], "resolved_accessions": ["GSE14333", "GSE17536", "GSE33113"], "statements": ["To increase the reliability of this result, we obtained the prognostic significance of GPR116 in GSE14333, GSE17536, and GSE33113 with a total of 197, 177, and 89 cases enrolled from the GEO datasets. We found that high GPR116 protein expression was obviously associated with reduced overall survival time (p=0, 0.03, and 0.001 respectively, Figure 3B-3D)."], "basis": "The paper names GSE14333, GSE17536, GSE33113 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["chi_square_test"], "assets": ["source:pmid:28624786", "data:geo:GSE14333", "asset:table:pmid:28624786:1", "asset:table:pmid:28624786:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14333"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:31:22Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 59140, "completion_tokens": 6900, "cached_tokens": 1832}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:28624786", "type": "paper", "label": "pmid:28624786"}, {"id": "source:pmid:28624786", "type": "manuscript", "label": "PMID 28624786 full text"}, {"id": "data:geo:GSE14333", "type": "dataset", "label": "GEO GSE14333"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:28624786", "type": "paper", "label": "pmid:28624786"}, {"id": "source:pmid:28624786", "type": "manuscript", "label": "PMID 28624786 full text"}, {"id": "data:geo:GSE14333", "type": "dataset", "label": "GEO GSE14333"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-28624786", "type": "extraction", "used": ["source:pmid:28624786"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14333", "type": "accession_resolution", "used": ["data:geo:GSE14333"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:28624786", "parent_hash": "sha256:d77967d3d13cde9f628f1c423820bfab09193c11b4347baab4a4e9b4f677a03d", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE14333 licence not read", "asset:data:geo:GSE14333 not downloaded", "asset:data:geo:GSE17536 licence not read", "asset:data:geo:GSE17536 not downloaded", "asset:data:geo:GSE33113 licence not read", "asset:data:geo:GSE33113 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may dri", "was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in C", "10% FBS at 37°C in an atmosphere of 5% CO2. Transfection of siRNA was performed using Lipofectamine 2", "ccording to the manufacturer's protocol. The transfection reagent was replaced by complete medium afte"], "order_basis": "paper_text_order:894", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in CRC according to its mRNA expression and immunohistochemical scoring. Results demonstrated that GPR116 wa", "ROC: receiver operating characteristic; IHC: immunohistochemical. MATERIALS AND METHODS Patients and tissue s", "e analysis according to GPR116 expression by IHC. ROC: receiver operating characteristic; IHC", "IHC. ROC: receiver operating characteristic; IHC: immunohistochemical. MATERIALS AND METHODS"], "order_basis": "paper_text_order:5171", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["CR, and another 6 samples were collected for western blot. This study was approved by the Ethics Commi"], "order_basis": "paper_text_order:7025", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["American Type Culture Collection. They were cultured in RPMI 1640 medium (Gibco, Gaithersburg, MD, U"], "order_basis": "paper_text_order:7463", "id": "assay:4"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We used the Chi-square test or Fisher's exact test to evaluate the correlation between GPR116 expression and corresponding patients’ clinicopathological parameters."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}