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pmid:41469955
Silencing TMEM105 suppresses gastric cancer cell growth and migration via proliferation-associated pathways.
Behnoosh Nikonezhad · Mobina Shahriarizade · Atefeh Zamani · Mohammad Mahdevar
BMC cancer · 2025 doi:10.1186/s12885-025-15522-w
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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In this study, the expression changes of TMEM105 in gastric cancer (GC) and its association with malignancy were examined.\nMETHODS: In the in silico section, TMEM105 expression in GC and its correlation with patient prognosis were analyzed using publicly available datasets. Using WGCNA analysis on TCGA data, modules and potential pathways associated with TMEM105 were identified. Expression changes of TMEM105 in GC tissues compared with adjacent healthy tissues were analyzed by RT-qPCR. The expression level of TMEM105 in GC cell lines, including AGS and MKN-45, was modulated using siRNA. The relationship between TMEM105 expression and malignant characteristics, including cell proliferation, migration, and colony formation, was examined in these cell lines.\nRESULTS: TMEM105 was significantly upregulated in public datasets, including TCGA, GSE19826, and GSE54129. TMEM105 expression was associated with advanced disease stage and poor prognosis. WGCNA analysis revealed that TMEM105 expression clustered with genes related to cell proliferation, such as E2F target genes, within the same module. Silencing TMEM105 reduced the viability of GC cell lines and decreased mRNA expression of proliferation-related genes, including E2F1, Cyclin D1, and Ki-67. Silencing TMEM105 markedly reduced migration rates in GC cells. Moreover, TMEM105 expression affected the colony-forming ability of these cell lines.\nCONCLUSION: High TMEM105 expression in GC is associated with poorer patient outcomes. It appears to influence cellular proliferation and contribute to the development and malignancy of gastric carcinoma. Consequently, TMEM105 could be a valuable therapeutic and prognostic target.", "claims": [{"id": "claim-method", "statement": "A Cox regression analysis was conducted to examine the association between TMEM105 expression and clinical outcomes. Further evaluation was carried out using Kaplan–Meier survival curves. For the Kaplan–Meier analysis, TCGA tumor samples were divided into high- and low-expression groups based on the median TMEM105 expression level. The log-rank test was employed to determine statistical significance in all survival analyses.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41469955", "locator": "sections[5] \"Survival analysis\" paragraph 2", "quote": "A Cox regression analysis was conducted to examine the association between TMEM105 expression and clinical outcomes. Further evaluation was carried out using Kaplan–Meier survival curves. For the Kaplan–Meier analysis, TCGA tumor samples were divided into high- and low-expression groups based on the median TMEM105 expression level. The log-rank test was employed to determine statistical significance in all survival analyses."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analyzed during the current study. The present investigation examined information from publicly accessible databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41469955", "locator": "sections[25] \"notes\" paragraph 1", "quote": "No datasets were generated or analyzed during the current study. The present investigation examined information from publicly accessible databases."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Analysis of public TCGA and GEO datasets found that TMEM105 was significantly upregulated in gastric cancer, and high expression was associated with advanced stage and poor prognosis.", "kind": "quantitative", "target": {"value": 1.29, "unit": "hazard ratio", "tolerance": null, "source": "Cox regression analysis revealed that high TMEM105 expression was associated with poor prognosis (hazard ratio = 1.29; P = 0.01). Moreover, Kaplan-Meier analysis indicated that samples with higher TMEM105 expression had a significantly lower survival rate (Fig. 1H; P = 0.02)."}, "evidence": [{"asset": "source:pmid:41469955", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "TMEM105 was significantly upregulated in public datasets, including TCGA, GSE19826, and GSE54129. TMEM105 expression was associated with advanced disease stage and poor prognosis."}, {"asset": "source:pmid:41469955", "locator": "sections[15] \"Increased expression ofTMEM105in GC and its association with advanced stage and poor patient survival\" paragraph 2", "quote": "Cox regression analysis revealed that high TMEM105 expression was associated with poor prognosis (hazard ratio = 1.29; P = 0.01). 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The expression level of TMEM105 in GC cell", "adjacent healthy tissues were analyzed by RT-qPCR. The expression level of TMEM105 in GC cell", "d with that in adjacent normal tissues using RT-qPCR. The ex vivo results demonstrated a signific", "adjacent healthy samples are presented using RT-qPCR. TMEM105 expression was significantly higher"], "order_basis": "paper_text_order:721", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ncluding AGS and MKN-45, was modulated using siRNA. The relationship between TMEM105 expression"], "order_basis": "paper_text_order:826", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["elated genes, including E2F1, Cyclin D1, and Ki-67. Silencing TMEM105 markedly reduced migratio"], "order_basis": "paper_text_order:1494", "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": 0.99, "evidence": ["ture Human GC cell lines AGS and MKN-45 were cultured in DMEM (Genex, Iran) medium supplemented with", "e cells reached 70–80% confluency, they were passaged using 0.25% trypsin-EDTA (DENAzist, Iran) an"], "order_basis": "paper_text_order:4173", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["A Cox regression analysis was conducted to examine the association between TMEM105 expression and clinical outcomes. Further evaluation was carried out using Kaplan–Meier survival curves. For the Kaplan–Meier analysis, TCGA tumor samples were divided into high- and low-expression groups based on the median TMEM105 expression level. The log-rank test was employed to determine statistical significance in all survival analyses."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}