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pmid:34319035

Prognostic Role of Receptor Tyrosine Kinase-Like Orphan Receptors in Intestinal-Type Gastric Cancer.

Rajeev Nema · Priti Patel · Ashok Kumar

Asian Pacific journal of cancer prevention : APJCP · 2021 doi:10.31557/APJCP.2021.22.7.2125

Paper

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Experiment

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Data

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Analysis

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title
Prognostic Role of Receptor Tyrosine Kinase-Like Orphan Receptors in Intestinal-Type Gastric Cancer.
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10.31557/APJCP.2021.22.7.2125
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Rajeev Nema
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Priti Patel
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Ashok Kumar
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Asian Pacific journal of cancer prevention : APJCP
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2021
abstract
BACKGROUND: Gastric cancer (GC) is diagnosed at advanced stages and has high mortality rates. Surgical resection and adjuvant chemotherapy are the main therapeutic approaches for GC. Despite curative resection, recurrence and metastasis contribute to a high mortality rate in patients with GC. The receptor-tyrosine-kinase-like orphan receptors 1/2 (ROR1/2) are transmembrane proteins belonging to the receptor tyrosine kinase (RTK) family. ROR1 and ROR2 are known to overexpress in the tumor tissues from several types of cancer patients. However, the role of RORs in the prognosis has not been understood. METHODS: This study aimed to determine the association of mRNA expression of ROR1, ROR2, and their signaling components WNT5A, NKX2-1, and FOXF1, with the survival outcome of GC patients. We performed Kaplan-Meir survival analysis on publicly available 'The Cancer Genome Atlas (TCGA)' data sets using 'Kaplan-Meir Plotter.' RESULTS: High mRNA expression of ROR1, ROR2, NKX2-1, and FOXF1 was significantly correlated with worse overall survival (OS) of GC patients. Interestingly ROR1 and ROR showed a prognostic role in the intestinal subtype, but not in the diffuse subtype of GC. Furthermore, ROR1 was positively correlated with regulatory T cells and M2-type macrophages and negatively correlated with Th17 and natural killer T cells in the tumor stroma of patients with GC. CONCLUSION: We conclude that the expression of ROR1, ROR2, and their associated genes correlate with worst prognosis of GC patients, particularly in the intestinal type.<br />.
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Despite curative resection, recurrence and metastasis contribute to a high mortality rate in patients with GC. The receptor-tyrosine-kinase-like orphan receptors 1/2 (ROR1/2) are transmembrane proteins belonging to the receptor tyrosine kinase (RTK) family. ROR1 and ROR2 are known to overexpress in the tumor tissues from several types of cancer patients. However, the role of RORs in the prognosis has not been understood.\nMETHODS: This study aimed to determine the association of mRNA expression of ROR1, ROR2, and their signaling components WNT5A, NKX2-1, and FOXF1, with the survival outcome of GC patients. We performed Kaplan-Meir survival analysis on publicly available 'The Cancer Genome Atlas (TCGA)' data sets using 'Kaplan-Meir Plotter.'\nRESULTS: High mRNA expression of ROR1, ROR2, NKX2-1, and FOXF1 was significantly correlated with worse overall survival (OS) of GC patients. Interestingly ROR1 and ROR showed a prognostic role in the intestinal subtype, but not in the diffuse subtype of GC. Furthermore, ROR1 was positively correlated with regulatory T cells and M2-type macrophages and negatively correlated with Th17 and natural killer T cells in the tumor stroma of patients with GC.\nCONCLUSION: We conclude that the expression of ROR1, ROR2, and their associated genes correlate with worst prognosis of GC patients, particularly in the intestinal type.<br />.", "claims": [{"id": "claim-method", "statement": "We performed Kaplan-Meir survival analysis on publicly available ‘The Cancer Genome Atlas (TCGA)’ data sets using ‘Kaplan-Meir Plotter.’", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34319035", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We performed Kaplan-Meir survival analysis on publicly available ‘The Cancer Genome Atlas (TCGA)’ data sets using ‘Kaplan-Meir Plotter.’"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The KM plotter (kmplot.com) is a widely used database for the meta-analysis of publicly available TCGA microarray datasets to identify prognostic biomarkers (Győrffy et al., 2013).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34319035", "locator": "sections[2] \"Materials and Methods\" paragraph 3", "quote": "The KM plotter (kmplot.com) is a widely used database for the meta-analysis of publicly available TCGA microarray datasets to identify prognostic biomarkers (Győrffy et al., 2013)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34319035"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8607102", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:34319035:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dd40b9194b4e1674e6255cea05aafbf3d4b2b67c38df9f41e5866395f00dfc55", "bytes": 886, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#T1", "version": null, "note": "Correlation between mRNA Expression of ROR1/2, NKX2-1, FOXF1, and WNT5A Genes and Different forms of Survival Outcome in GC Patients", "structure": {"pmcid": "PMC8607102", "section_index": 3, "section_title": "Results", "row_count": 16, "column_count": 5}, "table": {"label": "Table 1", "caption": "Correlation between mRNA Expression of ROR1/2, NKX2-1, FOXF1, and WNT5A Genes and Different forms of Survival Outcome in GC Patients", "rows": [["Gene", "Survival", "Patients", "Hazard ratio", "95% CI"], ["ROR1", "OS", "875", "1.41", "1.91-1.68"], ["", "FP", "640", "1.43", "1.17-1.76"], ["", "PPS", "498", "2.15", "1.71-2.7"], ["ROR2", "OS", "875", "1.41", "1.23-1.73"], ["", "FP", "640", "1.42", "1.16-1.74"], ["", "PPS", "498", "1.75", "1.36-2.12"], ["WNT5A", "OS", "875", "1.04", "0.88-1.23"], ["", "FP", "640", "1.24", "0.01-1.52"], ["", "PPS", "498", "0.98", "0.78-1.22"], ["NKX2-1", "OS", "875", "1.44", "1.21-1.71"], ["", "FP", "640", "1.37", "1.12-1.68"], ["", "PPS", "498", "1.55", "1.24-1.93"], ["FOXF1", "OS", "875", "1.42", "1.2-1.68"], ["", "FP", "640", "1.33", "1.08-1.63"], ["", "PPS", "498", "1.5", "1.25-1.93"]], "row_count": 16, "column_count": 5, "numeric_cells": 47, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We performed Kaplan-Meir survival analysis on publicly available ‘The Cancer Genome Atlas (TCGA)’ data sets using ‘Kaplan-Meir Plotter.’"}}, {"id": "method-2", "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 proportional hazards"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {"hazard_ratio": "Hazard ratio (HR) with 95% confidenc"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "targets": [], "gaps": []}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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