MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson’s correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.

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Investigation of the Relationship Between Delta Inflammatory Markers and Prognosis in Head and Neck Squamous Cell Carcinoma

10.1101/2021.04.29.21256130 ◽

2021 ◽

Author(s):

Julian Khaymovich ◽

Andrew Ko ◽

Amanda Wong ◽

Daniel Zhu ◽

Christian Gigante ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Multivariate Analysis ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Inflammatory Markers ◽

Hospital Setting ◽

Neck Squamous Cell Carcinoma ◽

Cancer Prognosis ◽

Lymphocyte Ratio

Purpose: Inflammatory markers, such as Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), have been shown to hold significant prognostic value in the context of head and neck cancer (HNC). Recently, delta inflammatory markers, the difference between pre and post- treatment inflammatory marker ratios, have been suggested as potentially significant values in predicting cancer prognosis. Our objective was to evaluate the prognostic utility of delta LMR, NLR, and PLR in head and neck squamous cell carcinoma (HNSCC). Methods: Retrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNSCC in the oral cavity, larynx, and oropharynx treated with curative intent treatment were included. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, ECOG score, and lab values. Overall Survival (OS) and Event-Free Survival (EFS) were chosen as endpoints. OS was defined as time from date of treatment to date of last follow-up or death from any cause, and EFS was defined as the start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate analyses were performed on the primary endpoints. Results: A total of 89 patients were included from 2010 to 2017. In multivariate analysis, EFS was found to be significantly associated with an N stage of 3 (p=0.0005) and delta LMR > -1.48 (p=0.0241). No significant relationships were uncovered with OS in multivariate analysis. Conclusion: A higher delta LMR value (>-1.48) was associated with poorer EFS, but was not associated with OS.

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