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pmid:34442426

A Transcriptomic Analysis of Head and Neck Squamous Cell Carcinomas for Prognostic Indications.

Li-Hsing Chi · Alexander T H Wu · Michael Hsiao · Yu-Chuan Jack Li

Journal of personalized medicine · 2021 doi:10.3390/jpm11080782

Paper

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Experiment

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Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
A Transcriptomic Analysis of Head and Neck Squamous Cell Carcinomas for Prognostic Indications.
doi
10.3390/jpm11080782
pmid
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Li-Hsing Chi
[1]
Alexander T H Wu
[2]
Michael Hsiao
[3]
Yu-Chuan Jack Li
journal
Journal of personalized medicine
year
2021
abstract
Survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method for discovering gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for patient dichotomization when using continuous gene expression values. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the medians or quantiles of gene expression values. There are also few clinicopathological features available in pre-processed datasets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustments with confounders, clinical tumor stage and surgical margin involvement were found to be independent risk factors for prognosis. According to the results tables that show hazard ratios with Bonferroni-adjusted p values under the optimal cutoff, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with overall survival. We validated this discovery by using the another independent HNSCC dataset (GSE65858). Thus, we suggest that transcriptomic analysis could help with biomarker discovery. Moreover, the robustness of the biomarkers we identified should be ensured through several additional tests with independent datasets.
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All data processing and analyses were performed with R programming language (https://www.r-project.org/, version 4.0.2, 22 June 2020) and R packages “firebrowseR,” “survival,” “reshape,” “data.table,” “ggplot2,” “R.utils,” “xlsx,” “r2excel,” “rJava,” and “rms” in an Rstudio server (version 1.2.5001) based on Google cloud platform in Linux (Ubuntu LTS, release v18.04.3). The R script code and datasets generated during the current study are available at the GitHub repository, https://github.com/texchi2/pvalueTex, accessed on 10 March 2021.
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Univariate/multivariate Cox proportional hazard regression analyses on OS time of CAMK2N1 gene expression in HNSCC.
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All data processing and analyses were performed with R programming language (https://www.r-project.org/, version 4.0.2, 22 June 2020) and R packages “firebrowseR,” “survival,” “reshape,” “data.table,” “ggplot2,” “R.utils,” “xlsx,” “r2excel,” “rJava,” and “rms” in an Rstudio server (version 1.2.5001) based on Google cloud platform in Linux (Ubuntu LTS, release v18.04.3). The R script code and datasets generated during the current study are available at the GitHub repository, https://github.com/texchi2/pvalueTex, accessed on 10 March 2021.
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A Transcriptomic Analysis of Head and Neck Squamous Cell Carc
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CC dataset (GSE65858). Thus, we suggest that transcriptomic analysis could help with biomarker discovery
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34442426", "kind": "science-record", "revision": 6, "content_hash": "sha256:d54cff8949ec5aee038ecf58df61122661d8a5f94655e09a8ac2281d576af358", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T21:26:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Transcriptomic Analysis of Head and Neck Squamous Cell Carcinomas for Prognostic Indications.", "doi": "10.3390/jpm11080782", "pmid": "34442426", "authors": ["Li-Hsing Chi", "Alexander T H Wu", "Michael Hsiao", "Yu-Chuan Jack Li"], "journal": "Journal of personalized medicine", "year": 2021, "abstract": "Survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method for discovering gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for patient dichotomization when using continuous gene expression values. There is some optimization software for cutoff determination. However, the software's predetermined cutoffs are usually set at the medians or quantiles of gene expression values. There are also few clinicopathological features available in pre-processed datasets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan-Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustments with confounders, clinical tumor stage and surgical margin involvement were found to be independent risk factors for prognosis. According to the results tables that show hazard ratios with Bonferroni-adjusted p values under the optimal cutoff, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with overall survival. We validated this discovery by using the another independent HNSCC dataset (GSE65858). Thus, we suggest that transcriptomic analysis could help with biomarker discovery. Moreover, the robustness of the biomarkers we identified should be ensured through several additional tests with independent datasets.", "claims": [{"id": "claim-method", "statement": "The Cox proportional-hazards regression model [117,118] is commonly used for modeling survival data.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34442426", "locator": "sections[21] \"4.3. 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Results", "row_count": 5, "column_count": 8}, "table": {"label": "Table 2", "caption": "The top 3 genes with prognostic impacts on HNSCC.", "rows": [["Gene ID", "Gene Description", "Kaplan–Meier Survival", "Cox Univariate", "Cox Multivariate"], ["FDR p Value", "Bonferroni p Value", "HR *", "CI95%", "HR *", "CI95%"], ["CAMK2N1", "calcium/calmodulin- dependent protein kinase II inhibitor 1", "1.63 × 10−5", "0.002", "2.101", "1.572–2.809", "2.007", "1.490–2.704"], ["CALML5", "calmodulin like 5", "1.97 × 10−4", "0.039", "0.51", "0.379–0.686", "0.493", "0.364–0.667"], ["FCGBP", "Fc fragment of IgG binding protein", "4.83× 10−5", "0.008", "0.484", "0.359–0.653", "0.496", "0.366–0.674"]], "row_count": 5, "column_count": 8, "numeric_cells": 22, "header_rows": 2, "locator": "section[2]/table-wrap[2]#jpm-11-00782-t002"}}], "gaps": []}, "analysis": {"state": "partial", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-2", "family": null, "specific": null, "label": "Cox proportional-hazards regression model", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Cox proportional-hazards regression model [117,118] is commonly used for modeling survival data."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All data processing and analyses were performed with R programming language (https://www.r-project.org/, version 4.0.2, 22 June 2020) and R packages “firebrowseR,” “survival,” “reshape,” “data.table,” “ggplot2,” “R.utils,” “xlsx,” “r2excel,” “rJava,” and “rms” in an Rstudio server (version 1.2.5001) based on Google cloud platform in Linux (Ubuntu LTS, release v18.04.3). 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Thus, we suggest that transcriptomic analysis could help with biomarker discovery", "nucleotide polymorphisms), RNA (microarray, RNA-Seq, microRNA), and protein (reverse protein pha", "ionary: Common Data Element (CDE) [107]. The RNA-Seq expression data have been harmonized and re-"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["allenging cancer research. Such in vitro and in vivo validation experiments will be undertaken in", "into these HNSCC candidates via in vitro and in vivo validation. We aim to promote a reproducible", "proliferation, migration, and invasion) and mouse xenograft models (e.g., tumor growth). 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