Abstract
Objective Cancer stem cells (CSCs) with self-renewal and plasticity contribute to tumor initiation and progression. This study developed an mRNA expression-based stemness index- (mRNAsi-) associated signature and validated biological functions of stem cell-related genes in oral squamous cell carcinoma (OSCC). Methods Here, mRNAsi was measured for OSCC samples from TCGA cohort, and prognosis and tumor microenvironment (stromal/immune scores, tumor purity) in high- and low-mRNAsi samples were evaluated with survival analyses and ESTIMATE algorithm. Based on prognostic mRNAsi-related genes, a risk score model was constructed by the LASSO method. The predictive accuracy was evaluated by uni- and multivariate Cox analyses and ROC curves. Among the genes in the model, the functions of H2AFZ on proliferation, apoptosis, invasion, and EMT were investigated in OSCC cells. Results High mRNAsi was distinctly associated with undesirable prognosis, increased stromal and immune scores, and lowered tumor purity. The mRNAsi-associated signature containing 11 genes was developed, and high-risk score was distinctly related to poor survival outcomes. Moreover, this signature was an independent and robust risk factor. H2AFZ upregulation significantly enhanced proliferative and invasive capacities and facilitated EMT as well as lowered apoptotic levels in Cal-27 and HSC-3 cells. Conclusion Our study characterized cancer stem cell characteristics that were closely related to tumor microenvironment and developed a stemness index cell-related signature that could assist prognosis prediction and risk stratification for OSCC. H2AFZ could become a potential therapeutic target against OSCC.
Highlights
Oral carcinoma represents a common malignancy among humans, with over 90% of cases deriving from oral squamous cell carcinoma (OSCC) [1]
We investigated the functions of mRNA expression-based stemness index- (mRNAsi-)related gene H2AFZ in OSCC cells
Increased infiltration levels of CD8+ T cell, activated memory CD4+ T cell, and resting NK cell were found in high-mRNA expression-based stemness index (mRNAsi) specimens (Figure 1(c))
Summary
Oral carcinoma represents a common malignancy among humans, with over 90% of cases deriving from oral squamous cell carcinoma (OSCC) [1]. Common risk factors contain tobacco, drinking, and human papilloma viruses [2]. Over 300,000 new cases of OSCC occur each year globally, and over 140,000 patients die of OSCC each year [3]. The five-year survival rate is merely 50% [4]. Most metastatic patients die within 12 months [5]. The conventional treatment for OSCC is a combination of curative resection, radiotherapy, and chemotherapy [6]. In the past 30 years, there has been no distinct progress in the treatment of OSCC
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