Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal Cancer.

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PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3-related genes. The correlation between PLOD3 expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of PLOD3 in CRC. What's more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. PLOD3 was highly expressed in many tumors including CRC. PLOD3 was upregulated in advanced stage CRCs, and high PLOD3 expression was associated with poor survival. High PLOD3 expression was associated with low levels of B cells, CD4+ T cells, M1 macrophages, CD8+ T cells, and multiple immunerelated characteristics. In addition, the high PLOD3 expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high PLOD3 expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of PLOD3 at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased PLOD3 expression in an immunotherapy treated dataset. PLOD3 is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high PLOD3 expression may be resistant to immune checkpoint therapy.", "claims": [{"id": "claim-method", "statement": "Differences in variables between groups were tested using the Wilcoxon test or chi-squared test, as appropriate. Kaplan-Meier curves were drawn to estimate the overall survival distribution. The log-rank test was used to analyze the statistical difference in survival curves between two groups. Kruskal-Wallis tests were used for comparing PLOD3’s expression difference among more than two comparison groups and Wilcoxon test was used for comparison between two groups. The ROC curve was plotted via “pROC” package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34646265", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "Differences in variables between groups were tested using the Wilcoxon test or chi-squared test, as appropriate. Kaplan-Meier curves were drawn to estimate the overall survival distribution. The log-rank test was used to analyze the statistical difference in survival curves between two groups. Kruskal-Wallis tests were used for comparing PLOD3’s expression difference among more than two comparison groups and Wilcoxon test was used for comparison between two groups. The ROC curve was plotted via “pROC” package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during this study are available in the TCGA database (https://portal.gdc.cancer.gov) (TCGA-COAD and TCGA-READ), GEO database (https://www.ncbi.nlm.nih.gov/geo) (GSE17536, GSE39582, GSE74602, and GSE113513).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34646265", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The datasets analyzed during this study are available in the TCGA database (https://portal.gdc.cancer.gov) (TCGA-COAD and TCGA-READ), GEO database (https://www.ncbi.nlm.nih.gov/geo) (GSE17536, GSE39582, GSE74602, and GSE113513)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PLOD3 was overexpressed in CRC tumor tissue compared with adjacent normal tissue in tissue-microarray immunohistochemistry (p-value = 4.2e-14).", "kind": "quantitative", "target": {"value": 4.0, "unit": "p-value", "tolerance": null, "source": "Grossly, PLOD3 was overexpressed in tumor parts comparing to normal specimens ( Figure 6F , p-value = 4.2e-14)."}, "evidence": [{"asset": "source:pmid:34646265", "locator": "sections[18] \"Validation of the Diagnostic and Prognostic Value of PLOD3\" paragraph 2", "quote": "Grossly, PLOD3 was overexpressed in tumor parts comparing to normal specimens ( Figure 6F , p-value = 4.2e-14)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "PLOD3 was overexpressed in CRC tumor tissue compared with adjacent normal tissue in tissue-microarray immunohistochemistry (p-value = 4.2e-14).", "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:34646265"], "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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