Integrative Multiomics Analyses Identify Molecular Subtypes of Head and Neck Squamous Cell Carcinoma with Distinct Therapeutic Vulnerabilities.

Substantial heterogeneity in molecular features, patient prognoses, and therapeutic responses in head and neck squamous cell carcinomas (HNSCC) highlights the urgent need to develop molecular classifications that reliably and accurately reflect tumor behavior and inform personalized therapy. Here, we leveraged the similarity network fusion bioinformatics approach to jointly analyze multiomics datasets spanning copy number variations, somatic mutations, DNA methylation, and transcriptomic profiling and derived a prognostic classification system for HNSCC. The integrative model consistently identified three subgroups (IMC1-3) with specific genomic features, biological characteristics, and clinical outcomes across multiple independent cohorts. The IMC1 subgroup included proliferative, immune-activated tumors and exhibited a more favorable prognosis. The IMC2 subtype harbored activated EGFR signaling and an inflamed tumor microenvironment with cancer-associated fibroblast/vascular infiltrations. Alternatively, the IMC3 group featured highly aberrant metabolic activities and impaired immune infiltration and recruiting. Pharmacogenomics analyses from in silico predictions and from patient-derived xenograft model data unveiled subtype-specific therapeutic vulnerabilities including sensitivity to cisplatin and immunotherapy in IMC1 and EGFR inhibitors (EGFRi) in IMC2, which was experimentally validated in patient-derived organoid models. Two signatures for prognosis and EGFRi sensitivity were developed via machine learning. Together, this integrative multiomics clustering for HNSCC improves current understanding of tumor heterogeneity and facilitates patient stratification and therapeutic development tailored to molecular vulnerabilities. Significance: Head and neck squamous cell carcinoma classification using integrative multiomics analyses reveals subtypes with distinct genetics, biological features, clinicopathological traits, and therapeutic vulnerabilities, providing insights into tumor heterogeneity and personalized treatment strategies.

Fascia iliaca compartment block versus no block for pain control after lower limb surgery: a meta-analysis.

BACKGROUND: The analgesic effect of fascia iliaca compartment block (FICB) versus no block (NB) after lower limb surgery (LLS) is still controversial, so we performed this meta-analysis. MATERIALS AND METHODS: By searching the PubMed, Embase and the Cochrane Library (last update by July 20, 2017), randomized controlled trials comparing the analgesic effect of FICB versus NB in patients receiving LLS were identified. The primary outcome was the pain scores at 4, 12, and 24 h after LLS. The dosage of morphine at 24 h was also collected. The side effect of anesthesia was assessed according to the occurrence rate of postoperative nausea and vomiting. RESULTS: Data from 7 clinical trials that included 508 patients were summarized. The results showed that patients receiving FICB had lower pain scores at 4 h (mean difference [MD]=-1.17; 95% CI=-2.30 to -0.05; P=0.041), 12 h (MD=-0.41; 95% CI=-0.76 to -0.05; P=0.026) and 24 h (MD=-0.96; 95% CI=-1.77 to -0.15; P=0.020) after LLS. Besides, FICB could reduce the dosage of morphine at 24 h (MD=-2.06; 95% CI=-3.82 to -0.30; P=0.022) and the incidence of postoperative nausea and vomiting (relative risk rate=0.44, 95% CI=0.24-0.80, P=0.008). CONCLUSION: Compared with NB, FICB is an effective and safe method for alleviating the pain after LLS. More high-quality randomized controlled trials are needed to confirm this finding.