Deciphering the value of anoikis-related genes in prognosis, immune microenvironment, and drug sensitivity of laryngeal squamous cell carcinoma

Abstract

Background

Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignancy characterized by high metastatic potential and poor prognosis. Anoikis, an apoptotic pathway triggered by detachment from the extracellular matrix (ECM), acts as a barrier against cancer metastasis, so it is necessary to explore the role of anoikis-related genes (ARGs) in LSCC.

Methods

Multivariate Cox regression analysis was used to construct prognostic model. A nomogram integrating risk scores with clinicopathological characteristics was constructed for prognosis. Spearman correlation analysis linked ARGs to the tumor microenvironment (TME) and immune infiltration. We also predicted IC50 values for various chemotherapeutic agents by risk group and selected three drugs (LGK974, OSI-027, and OF-1) for molecular docking with MMP3. TCGA datasets was used to evaluate the expression profile of MMP3 and TIMP1 in LSCC. In vitro assays were conducted to confirm the function of target gene in LSCC.

Results

We identified 19 ARGs associated with LSCC prognosis and developed a prognostic model, which subsequently classified patients into high- and low-risk groups based on median risk scores. Nomogram we established demonstrated excellent predictive performance. Low-risk individuals exhibited significantly higher immunophenotype (IPS) scores and elevated levels of immune cell components than high-risk counterparts (p < 0.05). MMP3 demonstrating strong binding affinity with selected drugs. Analysis of TCGA datasets revealed higher TIMP1 and MMP3 expression in LSCC tissues.

Conclusions

Our prognostic signature effectively predicts LSCC prognosis, with MMP3 identified as a potential novel biomarker for LSCC treatment. Furthermore, our findings underscore the critical role of immune-based therapies in improving outcomes, especially for low-risk patients.