CXCL family-related classification predicts prognosis and response to immunotherapy in patients with head and neck squamous cell carcinoma based on TCGA and GEO databases.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant cancer worldwide. The cysteine X cysteine (CXC) chemokine family contains 17 members, which are reportedly crucial for the growth, invasion, metastasis, and microenvironment of tumor cells. Although the precise functions of CXC ligands (CXCLs) in HNSCC are unclear, these proteins may play important roles in controlling tumor growth and forming the tumor immune environment. Methods: We downloaded the RNA sequencing and matched clinicopathological data of 379 patients with HNSCC as the training set from The Cancer Genome Atlas and two datasets from the Gene Expression Omnibus for use as validation sets. Results: Through consensus clustering, we identified two subtypes of HNSCC associated with the CXCL family, named cluster1 and cluster2. Patients with the cluster1 subtype showed favourable clinical outcomes, significant immune cell infiltration, and improved immune response signalling pathway modulation. We also developed a nomogram of CXCL family scores for therapeutic use and for predicting the overall survival (OS) of patients with HNSCC. Patients with lower scores showed longer OS and higher immune cell infiltration in their tissues. Conclusions: We developed a new classification method for HNSCC using the CXCL gene family, which can be used clinically to evaluate the prognosis and response to immunotherapy in patients with HNSCC.

Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis.

OBJECTIVE: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are new treatment for advanced non-small cell lung cancer. Here, we quantified the toxicity profiles of different ALK-TKIs to guide clinical decision making. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Data were analyzed using random effects and consistency models under the frequency framework. RESULTS: Of 865 relevant studies, 13 RCTs (encompassing 3,353 patients) were finally included. A network meta-analysis of all-grade AEs, fatal AEs, and treatment discontinuation due to AEs revealed no significant differences among the six ALK-TKIs. The rates of grade 3-4 AEs were: alectinib (16.2%), crizotinib (46.4%), brigatinib (63.7%), ensartinib (75.6%), ceritinib (78.3%), and lorlatinib (91.6%). The toxicity spectra of ALK-TKIs were different. The most frequent AEs associated with crizotinib were gastrointestinal reactions, visual disorders, neutropenia, edema, fatigue, and elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, while those in the alectinib group were anemia and constipation. Diarrhea, hepatotoxicity, and increased serum creatinine were most common with ceritinib. The most frequent AEs in the brigatinib group were gastrointestinal reactions, hypertension, cough, headache, and elevated ALT or AST levels. The most significant toxicities of ensartinib were skin disorders, including pruritus and rash. Changes in lipid levels were the most frequent AEs associated with lorlatinib; weight gain, cognitive effects, and mood effects were lorlatinib-specific AEs. CONCLUSIONS: The toxicity spectra of ALK-TKIs differed. Alectinib might be the safest ALK-TKI drug according to the combined evidence of grades 3-4 AEs and the combined incidence.

Classification of SLC family-related genes involved in ferroptosis predicts lung cancer prognosis and immunotherapy response.

Lung adenocarcinoma, the most frequent type of lung cancer, is the leading cause of cancer-related deaths worldwide. Ferroptosis, controlled cell death that involves a high degree of iron-dependent lipid peroxidation, has been linked to tumor therapy sensitivity, patient prognosis, and cancer development. The solute carrier superfamily has over 400 members and comprises the largest class of transporters in the human genome. Solute carrier proteins can facilitate the movement of different substrates across biological membranes, which is crucial for physiological activities, including ferroptosis. Here, we developed a new model to further explore the role of the solute carrier family in ferroptosis in the lung adenocarcinoma immunological milieu. We used consensus clustering to classify patients with lung cancer into two subgroups (cluster1 and cluster2). Patients in the cluster1 subtype had a better prognosis and higher immune cell infiltration ratios than those in the cluster2 subtype. Furthermore, to evaluate the prognosis, the immune cell infiltration ratio, and the medication sensitivity of patients with lung adenocarcinoma, we developed gene scores related to the solute carrier family. In conclusion, we successfully developed a model incorporating the solute carrier family and ferroptosis to predict survival and the impact of immunotherapy on patients with lung cancer.