Abstract
Aims: β-catenin is a critical regulating factor of the Wnt pathway, which is closely linked to tumorigenesis, tumor growth, metastasis, and tumor immunity. Our study focused on exploring the relationship between β-catenin and clinicopathological features, prognosis, as well as infiltrating immune cells and immune scores, so as to illustrate its clinical significance in NSCLC. Materials and Methods: The β-catenin mRNA (CTNNB1) and protein expression data were downloaded from the UALCAN and the UCSC Xena website, respectively. All tumor-immune infiltrating cells’ data were downloaded from the TIMER platform and immune scores were downloaded from ESTIMATE website. The expression of β-catenin protein in our cohort was measured by immunohistochemistry. Results: β-catenin mRNA level was higher in lung adenocarcinoma (LUAD) compared to normal tissues (p < 0.001) and was related to overall survival (OS) (p < 0.001) and post-progression survival (PPS) (both p = 0.049) in LUAD. Aberrant β-catenin protein expression was higher in male and lung squamous cell carcinoma (LUSC) patients (both p = 0.001). Also, it was considered to be a prognosis factor independently (p = 0.034). In addition, β-catenin protein was negatively correlated with CD8+T cells (r = −0.128, p = 0.008), neutrophils (r = −0.198, p < 0.001), immune score (r = −0.109, p = 0.024), stromal score (r = −0.097, p = 0.045), and ESTIMATE score (r = −0.113, p = 0.020). Conclusions: Aberrant β-catenin protein expression was evidently higher in NSCLC and might serve as a biomarker for poor prognosis. Most importantly, β-catenin protein might play an important part in tumor immunity and the tumor microenvironment by inhibiting the infiltration of CD8+ T cells and neutrophils.
Highlights
Lung cancer, which is one of the most principal malignant cancers with increasing incidence rates year by year, often occurs in bronchial mucosal epithelium and alveoli [1,2]
Immunocheckpoint inhibitor (ICI), represented by monoclonal antibodies against programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), can cause long-term remission and even cure 20–30% of patients
In order to explore β-catenin protein expression in our patient cohort, we used IHC to detect the subcellular localization and expression of β-catenin protein in NSCLC and Non-CLT. β-catenin protein was distributed in the cell membrane/cytoplasm, as well as in the nucleus (Figure 2)
Summary
Lung cancer, which is one of the most principal malignant cancers with increasing incidence rates year by year, often occurs in bronchial mucosal epithelium and alveoli [1,2] It is divided into SCLC (smallcell lung cancer) and NSCLC (non-small cell lung cancer), and further divided into squamous cell carcinoma, adenocarcinoma, and large-cell lung cancer [3]. Immunocheckpoint inhibitor (ICI), represented by monoclonal antibodies against programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), can cause long-term remission and even cure 20–30% of patients. It is a further sign of revolutionary progress in the field of lung cancer treatment, but not all patients can benefit from immunotherapy, and the overall effective rate is low [7,8]. It is urgent to study the exact pathogenesis of non-small cell lung cancer and find accurate biomarkers for predicting prognosis and searching for new clues for therapeutic targets
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