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

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.

Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer

“…Recent studies have found that FCGBP is expressed in 33 carcinomas compared with surrounding normal tissues (66). Moreover, it is significantly highly expressed in invasive breast carcinoma, diffuse large B-cell lymphoma, glioblastoma multiforme, lung adenocarcinoma, pancreatic adenocarcinoma, rectal adenocarcinoma, ovarian carcinoma, lower grade glioma, gastric cancer, and Human Papillomavirus (HPV)-infected patients with head and neck squamous cell carcinoma (HNSCC) (66)(67)(68)(69). Of these, the overexpression of this molecule usually predicts poor prognosis in ovarian carcinoma and lower-grade glioma (67).…”

“…Thus, Stranik speculates that FCGBP may be used as a novel diagnostic marker for intraamniotic infection in the two forms of natural preterm births (10). In contrast, a significant downregulation of FCGBP is found in adrenocortical carcinoma, chromophobe kidney cancer, clear cell kidney carcinoma, HNSCC and rectum adenocarcinoma, and cutaneous skin melanoma (66)(67)(68). Similarly, the expression of FCGBP is downregulated in colon cancer than that of surrounding normal tissues.…”

Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma

“…For all patients the ability to identify residual disease and discriminate between responders and non-responders would greatly enhance treatment effectiveness. Recent work has revealed several potential molecular markers of aggressive SCCs, including nucleic acids [ 42 , 43 , 44 ], and proteins [ 45 , 46 ]. Notably, recent analysis of data generated by transcriptome analysis [e.g., The Cancer Genome Atlas (TCGA) Research Network, (accessed on 9 September 2022)] [ 47 ], as well as a growing body of work in related preclinical (cell culture & animal) models, strongly suggests that the specific and differential expression of chondroitin sulfate (CS) proteoglycan 4 (CSPG4) may be used a potential marker of clinical course in SCCs.…”

“…To compare expression between cancer and control (noncancer) tissues one-way ANOVA was used (α = 0.05). Transcriptome data from recent public data on RDEB SCCs and cell lines was also reanalysed [ 43 , 44 ], using nonparametric Mann–Whitney U analysis (α = 0.05), to compare medians (α = 0.05). Survival analysis was conducted using Kaplan–Meier survival (α = 0.05), and comparison of tumour stage using one-way ANOVA (α = 0.05).…”

Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma

“…For all patients the ability to identify residual disease and discriminate between responders and non-responders would greatly enhance treatment effectiveness. Recent work has revealed several potential molecular markers of aggressive SCCs, including nucleic acids [42][43][44], and proteins [45,46]. Notably, recent analysis of data generated by transcriptome analysis [e.g., The Cancer Genome Atlas (TCGA) Research Network (www.cancer.gov/tcga)] [47], as well as a growing body of work in related preclinical (cell culture & animal) models, strongly suggests that the specific and differential expression of chondroitin sulfate (CS) proteoglycan 4 (CSPG4) may be used a potential marker of clinical course in SCCs.…”