Prognostic DNA mutation and mRNA expression analysis of perineural invasion in oral squamous cell carcinoma.

This study analyzed oral squamous cell carcinoma (OSCC) genomes and transcriptomes in relation to perineural invasion (PNI) and prognosis using Cancer Genome Atlas data and validated these results with GSE41613 data. Gene set enrichment analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted. We identified 22 DNA mutations associated with both overall survival (OS) and PNI. Among them, TGFBR1 and RPS6KA4 mRNAs were overexpressed, while TYRO3 and GPR137 mRNAs were underexpressed in PNI patients. Among the 141 mRNA genes associated with both OS and PNI, we found overlap with PNI-related DNA mutations, including ZNF43, TEX10, TPSD1, and PSD3. In GSE41613 data, TGFBR1, RPS6KA4, TYRO3, GPR137, TEX10 and TPSD1 mRNAs were expressed differently according to the prognosis. The 22 DNA-mutated genes clustered into nervous system development, regulation of DNA-templated transcription, and transforming growth factor beta binding. GSEA analysis of mRNAs revealed upregulation of hallmarks epithelial mesenchymal transition (EMT), TNFα signaling via NF-κB, and IL2 STAT5 signaling. EMT upregulation aligned with the TGFBR1 DNA mutation, supporting its significance in PNI. These findings suggest a potential role of PNI genes in the prognosis of OSCC, providing insights for diagnosis and treatment of OSCC.

Prognostic Genomic Markers of Pathological Stage in Oral Squamous Cell Carcinoma.

BACKGROUND: To identify the prognostic markers of oral squamous cell carcinoma (OSCC), the genetic heterogeneity of the pathological stages was investigated. METHODS: The data of 295 patients with primary OSCC obtained from the Cancer Genome Atlas were studied. The genetic prognostic landscape of the pathological stages was systematically analyzed by Cox regressions, Fisher's exact tests, and Gene Ontology (GO) enrichment. RESULTS: Stage 4 patients had a poor prognosis in univariate and multivariate Cox models. Transforming growth factor-beta (TGF-ß) pathway alterations were found more frequently in stage 4, whereas alterations in cell cycle pathways were significant in stages 1, 2, and 3. The differentially mutated genes were divided into three groups: risk genes of high stage, hazardless genes, and risk genes of low stage. The risk genes of low stage (RNF112, AKR7L, ZSCAN5C, and ZPBP) were independent prognostic factors with stage 4 and treatment modality in multivariate Cox regressions. Additionally, in genetic interaction analysis, NOMO1 and ZNF333 had a high co-occurrence in high stage, and WIZ had high co-occurrence in low stage. In GO enrichment, the prognostic genes were clustered at the functional term of RNA polymerase II transcription, and ZNF333 had an association with RNA transcription. CONCLUSION: The genetic mutation type and ratio of tumor heterogeneity are different for each stage of OSCC, and stratification of OSCC patients with differential therapeutic efficacy is needed. Risk genes of both high and low stages must be identified in patients diagnosed with low-stage OSCC. Mutations in NOMO1, ZNF333, and WIZ should be considered as potential prognostic markers.

Staging significance of bone invasion in small-sized (4cm or less) oral squamous cell carcinoma as defined by the American Joint Committee on Cancer.

OBJECTIVES: The staging significance of bone invasion is controversial in oral squamous cell carcinoma (OSCC) cases with tumors measuring 4cm or less according to the American Joint Committee on Cancer (AJCC). Our aim was to retrospectively examine a large group of patients with OSCC to determine the staging significance of bone invasion. MATERIALS AND METHODS: Three hundred and twenty-three patients with primary OSCC were classified based on tumor size. Bone invasion was categorized as absent, one side bone, and both buccal and lingual bones, and analyzed for association with disease progression. Regional lymph node metastasis (N), perineural invasion, vascular invasion, surgical margin involvement, and adjuvant treatment were also analyzed. RESULTS: In all OSCC cases, bone invasion (p=0.007) with stage N, perineural invasion, and surgical margin involvement were significant independent prognostic factors of disease progression. However, in OSCC cases with tumors measuring 4cm or less, bone invasion was not significantly associated with disease progression. Nevertheless, invasion of both buccal and lingual bones was significantly associated with disease progression (p=0.03). In multivariate analysis, both buccal and lingual bone invasion (p=0.04; hazard ratio=3.4; 95% confidence interval, 1.0-11.0), stage N2, and perineural invasion were also independent prognostic factors. CONCLUSION: Although OSCC bone invasion was an independent prognostic factor, bone invasion in small OSCC was not. However, small OSCC with both buccal and lingual bone invasion had a significantly worse prognosis. The AJCC T system is of limited prognostic value for small OSCC with bone invasion. But other elements should be examined before a modification can be accepted.

Facial Psoriasis Log-based Area and Severity Index: A valid and reliable severity measurement method detecting improvement of facial psoriasis in clinical practice settings.

Facial psoriasis is often observed in moderate to severe degrees of psoriasis. While we previously demonstrated construct validity of the facial Psoriasis Log-based Area and Severity Index (fPLASI) system for the cross-sectional evaluation of facial psoriasis, its reliability and accuracy to detect clinical improvement has not been confirmed yet. The aim of this study is to analyze whether the fPLASI properly represents the range of improvement for facial psoriasis compared with the existing facial Psoriasis Area and Severity Index (fPASI) after receiving systemic treatments in clinical practice settings. The changing severity of facial psoriasis for 118 patients was calculated by the scales of fPASI and fPLASI between two time points after systemic treatments. Then, percentage changes (ΔfPASI and ΔfPLASI) were analyzed from the perspective of both the Physician's Global Assessment of effectiveness (PGA) and patients' Subjective Global Assessment (SGA). As a result, the distribution of the fPASI was more heavily clustered around the low score range compared with the fPLASI at both first and second visits. Linear regression analysis between ΔfPASI and ΔfPLASI shows that the correlation coefficient was 0.94, and ΔfPLASI represented greater percentage changes than ΔfPASI. Remarkably, degrees of clinical improvement measured by the PGA matched better with ΔfPLASI, while ΔfPASI underestimated clinical improvements compared with ΔfPLASI from treatment-responding groups by the PGA and SGA. In conclusion, the fPLASI represented clinical improvement of facial psoriasis with more sensitivity and reliability compared with the fPASI. Therefore, the PLASI system would be a viable severity measurement method for facial psoriasis in clinical practice.

Prognostic significance of nestin in primary malignant melanoma of the oral cavity.

Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.