Background: Male patients with papillary thyroid carcinoma (PTC) tend to have poorer prognosis compared to females, partially attributable to a higher rate of lymph node metastasis (LNM). Developing a precise predictive model for LNM occurrence in male PTC patients is imperative. While preliminary predictive models exist, there is room to improve accuracy. Further research is needed to create optimized prognostic models specific to LNM prediction in male PTC cases. Methods: We conducted a comprehensive search of publicly available microarray datasets to identify candidate genes continuously upregulated or downregulated during PTC progression in male patients only. Univariate Cox analysis and lasso regression were utilized to construct an 11-gene signature predictive of LNM. TIPARP emerged as a key candidate gene, which we validated at the protein level using immunohistochemical staining. A prognostic nomogram incorporating the signature and clinical factors was developed based on the TCGA cohort. Results: The 11-gene signature demonstrated good discriminative performance for LNM prediction in training and validation datasets. High TIPARP expression associated with advanced stage, high T stage, and presence of LNM. A prognostic nomogram integrating the signature and clinical variables reliably stratified male PTC patients into high and low recurrence risk groups. Conclusions: We identified a robust 11-gene signature and prognostic nomogram for predicting LNM occurrence in male PTC patients. We propose TIPARP as a potential contributor to inferior outcomes in males, warranting further exploration as a prognostic biomarker and immunotherapeutic target. Our study provides insights into the molecular basis for gender disparities in PTC.

Background. This study is aimed at evaluating the diagnostic efficacy of ultrasound-based risk stratification for thyroid nodules in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) risk stratification systems. Methods. 286 patients with thyroid cancer were included in the tumor group, with 259 nontumor cases included in the nontumor group. The ACR TI-RADS and ATA risk stratification systems assessed all thyroid nodules for malignant risks. The diagnostic effect of ACR and ATA risk stratification system for thyroid nodules was evaluated by receiver operating characteristic (ROC) analysis using postoperative pathological diagnosis as the gold standard. Results. The distributions and mean scores of ACR and ATA rating risk stratification were significantly different between the tumor and nontumor groups. The lesion cm subgroup had higher malignant ultrasound feature rates detected and ACR and ATA scores. A significant difference was not found in the ACR and ATA scores between patients with or without Hashimoto’s disease. The area under the receiver operating curve (AUC) for the ACR TI-RADS and the ATA systems was 0.891 and 0.896, respectively. The ACR had better specificity (0.90) while the ATA system had higher sensitivity (0.92), with both scenarios having almost the same overall diagnostic accuracy (0.84). Conclusion. Both the ACR TI-RADS and the ATA risk stratification systems provide a clinically feasible thyroid malignant risk classification, with high thyroid nodule malignant risk diagnostic efficacy.

Immunotherapy with checkpoint inhibitors produced significant clinical responses in a subset of cancer patients who were resistant to prior therapies. However, Castration-resistant prostate cancer (CRPC) is seriously lack of T cell infiltration, which greatly limits the clinical application of immunotherapy, but the mechanism is unclear. In the present study, in silico analyses and experimental data show that HnRNP L was significantly negatively correlated with CD4+ and CD8+ T cells infiltration in patients; besides, we found deficiency of HnRNP L recruites CD4+ and CD8+ T cells infiltration and impairs tumorigenesis. Mechanically, HnRNP L enhanced the translation of c-Myc and then promoted CXCL8 secretion via alternative splicing of EIF4G1. In vivo, inhibition of EIF4G1 by the inhibitor, SBI-0640756, attenuated HnRNP L-induced tumor progression and immunosuppressive activity. And most of all, therapeutic synergy between HnRNP L knockdown and Anti-PD-1 could significantly suppress xenograft prostate cancer growth. In summary, this study revealled the molecular mechanism of HnRNP L regulating the immune infiltration, which provides a new theoretical basis for overcoming the limitation of immunotherapy for CRPC.