Given the complex of anatomical structure and daily functions in the head and neck area, HNSCC patients would face disabilities, so much as losing working ability, which can also affect families [24]. Thus, we are committed to exploring new treatment options, in order to increase the choice of treatments methods and construct prognosis model for HNSCC patients. In recent year, there have been substantial significant researches on the screening of IRGPI and clinical drug based on TCGA mRNA sequence, but the accuracy of survival estimation and the number patients who benefit were still limited [25–28]. In this study, we developed an IRGPI model based on TCGA-HNSCC and validated by GEO database and histological experiment. We further explored the immune cell distribution and immune cell infiltration and further stratified clinically defined groups of patients (e.g., clinical stage and pathological graded) into subgroups with different survival outcomes. In this research, we explored potential molecular biomarkers related to treatment efficacy so as to provide a newly prognostic biomarker for HNSCC patients.
As we all know, many researchers focused on tumor immunity, believing that it promoted tumor immune microenvironment and the development of immunotherapy, which means we harvested a deeper understanding of HNSCC development and treatment. But, unfortunately, the impact of effective complete immunotherapy database on the survival outcome of HNSCC patients are lacking, which need more researchers to collect and disposal data. Jingrun Yanga, used cluster and PCA analysis, identified six immunity genes signature for predicting the prognosis of HNSCC [5]. Yue Chen1, reported that they developed a prognostic marker to predict the prognosis of both conventional therapy and immunotherapy[25]. Hyun Chang, CD200R1, a variety of immune mechanisms, is related to an immune-rich microenvironment with high immune cell estimates [12]. No matter how mutated the germline genetic information, it would reshape the tumor microenvironment functional mechanisms and modulatory genes process[29]. Ultimately, achievements in scientific research could lead to the development of personalized therapeutic strategies. In this research, we identified 3 key Immune-related prognostic genes from 525 HNSCC patients. Three of seven IRGPI were reported to be involved in tumorigenesis and progression, but there have been few regarded reports and lacking tissue and cytological experiments. The higher level of DEFB1 targeted inhibition of PI3K/mTOR signaling pathway to effectively antitumor [30]. SEMA3G also take part in tumor of reproductive system and nervous system [31, 32]. The higher expression PTX3 would promote esophageal squamous cell carcinoma occurrence and promote cancer migrate by a toll-like receptor 4 (TLR4)/NF-kappaB signaling pathway [33, 34]. The difference of disease prognosis and tumor clinical stage showed the various situation of PTX3 expression [33, 35]. Research suggested that PTX3 affect the prognosis of tumor by regulating stem cell and macrophage polarization [36]. Other studies have shown that PTX3 can promote epidermal growth factor secretion to enhance head and neck cellular biological behavior [37, 38]. Therefore, we hope our results would help to identify the IRGPI risk model for HNSCC, providing insights into the development of novel biomarkers and further research into individualized targeted drug therapy.
In this research, according to the result of cibersort and ssGSEA, we found the different expression of risk gene influence immune cell distribution and immune cell infiltration, which can be exploited to promote tumor cells metastasis, angiogenesis, and growth. Besides, these were also affected the survival of HNSCC patients, which made explore effectiveness of the response to immunotherapy meaningfully. The immune system can produce immunosuppressive mediators and promote immunomodulatory cell types to evade the host immune in HNSCC [39]. In head and neck cancer, different anatomical subsite and etiological anent will be infiltrated variously by the extent and composition of the immune cell [40]. A recent study suggested stromal components played an important role in the development, establishment, and progression of HNSCC [41]. The tumor microenvironment was consisted of tumor cells and stromal cells, which include endothelial cells, cancer-associated fibroblasts (CAFs) and immune cells [41]. Each ingredient performs a variety of functions to influence the occurrence and development of tumors. For example, Cancer-associated fibroblasts (CAFs) can stimulate phenotypic transformation and secrete a broad range of growth factors[42]. In addition, in recent study, pirfenidone was regarded as potential drug in suppressing invasion and potentially metastasis in breast cancer [13]. Tumor-associated macrophages (TAMs) also could be induced M2-polarization by cytokines released by tumor cells [43]. Thus, the prognosis of tumor patients may not only due to the changes expression of genes in tumor cells but also tumor microenvironment especially the stromal composition of the HNSCC, which maybe provide a newly clinical intervention.
We tried to include more databases to rigorously validation our biomarkers, but survival data sets and ICI therapy effectiveness in HNSCC were not so much available. In addition, according to the etiology and site of disease leading to heterogeneity in tumor prognosis, multiple omics studies may be more conducive in assessing the risk and prognosis of HNSCC [44]. More functional experiments in laboratory and more clinical trials need to verify this risk model. And the interaction analysis with the characteristic risk factors of HNSCC need further verify in the future, such as smoking, HPV infection and TP53 highly expression.