Downregulation of T-cell cytotoxic marker IL18R1 promotes cancer proliferation and migration and is associated with dismal prognosis and immunity in lung squamous cell carcinoma

Abstract

Immunotherapy can improve the survival of patients with advanced lung squamous cell carcinoma (LUSC). T cytotoxic cells are one of the main members of the immune microenvironment. Herein, we aimed to identify the roles of T-cell cytotoxic markers interleukin 18 (IL18) receptor 1 (IL18R1) in the LUSC progression using bioinformatics, clinical tissue specimen, and cell experiment. We assessed the association between the IL18R1 expression and immune infiltration and IL18R1-related competing RNA network. The IL18R1 expression was downregulated in the LUSC tissues. The IL18R1 expression downregulation was associated with diagnosis and short overall survival and disease-specific survival, and it was also an independent risk factor for dismal survival time in LUSC. IL18R1-related nomograms predicted the survival time of patients with LUSC. IL18R1 overexpression inhibited the proliferation, migration, and invasion of LUSC cells. The IL18R1 expression was significantly associated with the microenvironment (stromal, immune, and estimate scores), immune cells (such as the T cells, cytotoxic cells, CD8 T cells), and immune cell markers (such as the CD8A, PD-1, and CTLA4) in LUSC. AC091563.1 and RBPMS-AS1 downregulation was positively associated with the IL18R1 expression, negatively associated with the miR-128-3p expression, and associated with short disease-specific survival and progression in LUSC. In conclusion, IL18R1 was significantly downregulated and associated with the prognosis and immune microenvironment. IL18R1 overexpression inhibits the growth and migration of cancer cells in LUSC. Furthermore, AC091563.1 and RBPMS-AS1 might compete with IL18R1 to bind miR-128-3p for participating in LUSC progression. These results showed that IL18R1 is a biomarker for evaluating the prognosis of patients with LUSC.

Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients

“…Immunotherapy is a promising treatment that can improve the quality of life and survival time of cancer patients [26][27][28]. For example, Zhang et al demonstrated that combining PDCD1/CD274 inhibitors with chemotherapy improved pCR, EFS, and OS in triple-negative breast cancer.…”

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis

“…SLC7A8 expression in LUAD tissues was investigated using the t -test [ 29 ]. The diagnostic value of SLC7A8 in LUAD was analyzed by computing the area under the ROC curves.…”

Overexpression of TMEM150A in glioblastoma multiforme patients correlated with dismal prognoses and compromised immune statuses

“…Variables with a significance level of P<0.05 were further subjected to multivariate Cox regression analysis. Additionally, nomograms were used as a tool to evaluate the prognosis of patients with cancer [14][15][16]. Thus, nomograms were developed based on the results of the multivariate Cox regression analysis, enabling the prediction of prognosis among patients with GBM.…”

“…and TMEM150A overexpression were significant predictors of poor prognosis in patients with GBM (Tables 2-4). The nomograms effectively helped visualise the prognosis and survival outcomes of patients with cancer [14][15][16]. Therefore, nomograms were constructed for OS, DSS, and PFI in patients with GBM based on the IDH status and TMEM150A expression levels (…”