Tongue squamous cell carcinoma (TSCC) is one of the deadliest cancers of the head and neck, but the role of the ferroptosis pathway in its development is still unknown. In this study we explored the pathogenetic mechanisms associated with ferroptosis in TSCC. We identified differentially expressed genes (DEGs) of TSCC patients and used gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to annotate, visualize, and integrate these DEGs. Receiver operating characteristic curve (ROC) analysis was performed, and the STRING database was used to construct a protein–protein interaction network to evaluate the predictive value of ferroptosis‐related DEGs. A total of 219 DEGs were identified and GO, KEGG, and GSEA showed that extracellular matrix (ECM)‐receptor interaction and interleukin (IL)‐17 signaling pathways were substantially upregulated in TSCC. Univariate Cox analysis revealed that high expression of CA9, TNFAIP3, and NRAS were predictive of a worse outcome. We then constructed a prognostic model that predicted survival in the validation cohort at 1 year and 32 months. Finally, 60 cases of tongue carcinoma and normal tissues were collected, and immunohistochemistry was used to detect the expression of CA9. We found that CA9 was strongly expressed in tongue carcinoma tissues and absent in adjacent tissues. Overall, we found that ferroptosis‐related genes may affect TSCC prognosis through the ECM‐receptor interaction and IL‐17 signaling pathways. Additionally, immunohistochemistry confirmed that CA9 was highly expressed in tongue carcinoma tissues, and a model based on ferroptosis‐related genes showed a good ability to predict overall survival in TSCC.

Background: Thyroid and breast cancers are the two most frequent types of endocrine-related tumors among women worldwide, and their incidence is still on the rise. Observational studies have shown a relationship between thyroid and breast cancers. Nevertheless, many confounders predispose the results to interference. Accordingly, we performed a two-sample Mendelian randomization (MR) study to investigate the causal association between thyroid and breast cancers.Methods: We acquired breast cancer data from the UK Biobank (13,879 breast cancer cases and 198,523 controls) and the Breast Cancer Association Consortium (BCAC; 122,977 breast cancer cases and 105,974 controls), and thyroid cancer data from FinnGen Biobank (989 thyroid cancer and 217,803 controls). Then, the multiplicative random effects inverse variance weighting (IVW), weight median (WM), and MR Egger methods were executed for MR analysis.Results: Overall, IVW showed a causal effect of breast cancer on thyroid cancer using the BCAC dataset (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.036–1.322; P = 0.011), and this relationship was also supported by the UK Biobank dataset (OR = 23.899; 95% CI = 2.331–245.003; P = 0.007), which showed that breast cancer patients were more likely to be diagnosed with thyroid cancer. On the whole, the reverse MR analysis did not show a causal effect of breast cancer on thyroid cancer. However, IVW showed a causal effect of thyroid cancer on estrogen receptor -negative breast cancer using the BCAC dataset (OR = 1.019; 95% CI = 1.001–1.038; P = 0.043), which suggested that people with thyroid cancer were more likely to develop breast cancer.Conclusions: Breast cancer represents a possible risk factor for thyroid cancer and thyroid cancer also represents a possible risk factor for ER-negative breast cancer. Future studies using powerful genetic tools to determine the causal relationship between breast and thyroid cancers are required.

Original Article Clinical outcomes of hepatocellular carcinoma patients after hepatectomy treated with TACE in combination with sorafenib: a propensity score matched analysis Yujie Li, Ruichen Zhao, Xiao Li

Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors. The presence of oral mucosal rupture and ulcerative lesions, which are the defining features of this condition, can significantly affect the quality of life of patients. Additionally, it can interfere with tumor therapy and contribute to an unfavorable prognosis. Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development. Moreover, thalidomide (THD) has been revealed to reduce the incidence and severity of RIOM in patients undergoing chemoradiotherapy for nasopharyngeal carcinoma. However, the mechanism through which THD improves RIOM remains unknown. This study aimed to investigate the role of LZTS3 in RIOM by analyzing various sequencing datasets and conducting knockdown and overexpression experiments. We used small interfering RNA transfection and LZTS3 overexpression, followed by validation through polymerase chain reaction, western blotting, flow cytometry, and enzyme-linked immunosorbent assay. In this study, we identified LZTS3 as a potential target for THD regulation in RIOM. Through a series of experiments, we confirmed that LZTS3 has the ability to inhibit the inflammatory response and apoptosis of cells. In addition, we also found that THD can regulate the expression of LZTS3 by upregulating, thereby affecting inflammatory response and apoptosis. We repeated these results in a live animal model. In summary, THD has the potential to reduce the occurrence of oral mucositis in patients by upregulating LZTS3 levels. These findings provide a promising avenue for future drug research and development to treat RIOM.

Hepatocellular carcinoma (HCC) ranks as a leading global cause of cancer-related mortality. Our study investigates the functional role between CD8⁺CD101⁺TIM3⁺ T cells (CCT) and CD8⁺CD101⁻TIM3⁺ T cells in HCC, with a focus on their implications for immunotherapy. We utilized single-cell RNA sequencing (scRNA-seq) to delineate the transcriptional landscapes and intercellular crosstalk of CCT and CD8⁺CD101⁻TIM3⁺ T cells in HCC tissues. Clinical characteristics and scRNA-seq data were curated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. For the differentially expressed genes (DEGs), Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment were performed. Prognostic model was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression model, validated through Kaplan-Meier survival curves and receiver operating characteristic (ROC) curves. A corresponding nomogram was also established to predict the prognosis of HCC patients. Our results indicated that T cell re-clustering revealed four functionally distinct subsets: CD8⁺ T cells, CD8⁺CD101⁻TIM3⁺ T cells, CCT, and CD4⁺ T cells. Pseudotime trajectory analysis demonstrated that CD8⁺CD101⁻TIM3⁺ T cells progressively differentiated into CCT, a process mediated by MIF-CD74/CXCR4 and SPP1-CD44 signaling axes. Enrichment analysis identified 1,281 CCT-specific genes enriched in mitochondrial electron transport and oxidative phosphorylation pathways. The prognostic model showed strong discriminatory power for overall survival (OS), achieving areas under the curve of 0.825, 0.873, and 0.865 at 1, 3, and 5 years in the training cohort, compared to 0.654, 0.636, and 0.644 in the validation cohort. The developed nomogram effectively predicts OS for HCC patients. Our findings elucidate the functional alterations of CCT and precursor cells within the context of HCC. The novel prognostic framework provides actionable insights for stratifying patients likely to benefit from combinatorial immunotherapy and chemotherapy.