Androgen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear. To explore the effects of ADT on PCa TIM, RNA sequencing was performed on six paired pre-ADT biopsy and post-ADT PCa lesions, and five paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa. Bioinformatics methods including ESTIMATE and ssGSEA were used to evaluate the stromal immune score and immune cell infiltration in PCa and paracancerous tissues. Weighted correlation network analysis was used to screen hub genes in the ADT-induced immune remodeling process. The results showed differences exist between PCa and paracancerous tissues in response to ADT. Compared with paracancerous tissues, the immune remodeling effect of ADT in PCa was more intense. ZFP36, JUNB, and SOCS3 served as hub genes in the ADT-induced immune remodeling process and were associated with PSA recurrent-free survival in the TCGA and our neoadjuvant ADT cohort. To investigate the joint action of the above three hub genes, an immune signature score was constructed. The results showed that immune signature score-based immune subtypes reveal the heterogeneity of the immune microenvironment of PCa and showed significant differences in patient prognosis, tumor immune infiltration, mutation burden, and landscape.
Lung cancer is the leading cause of cancer-related deaths mainly attributable to metastasis, especially extrathoracic metastasis. This large-cohort research is aimed to explore metastatic profiles in different histological types of lung cancer, as well as to assess clinicopathological and survival significance of diverse metastatic lesions. Lung cancer cases were extracted and enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. χ 2 -tests were conducted to make comparisons of metastatic distribution among different histological types and odds ratios were calculated to analyze co-occurrence relationships between different metastatic lesions. Kaplan-Meier methods were performed to analyze survival outcomes according to different metastatic sites and Cox regression models were conducted to identify independent prognostic factors. In total, we included 159,241 lung cancer cases with detailed metastatic status and complete follow-up information. In order to understand their metastatic patterns, we elucidated the following points in this research: (1) Comparing the frequencies of different metastatic lesions in different histological types. The frequency of bone metastasis was highest in adenocarcinoma, squamous cell carcinoma, LCLC and NSCLC/NOS, while liver was the most common metastatic site in SCLC. (2) Elaborating the tendency of combined metastases. Bi-site metastases occurred more common than tri-site and tetra-site metastases. And several metastatic sites, such as bone and liver, intended to co-metastasize preferentially. (3) Clarifying the prognostic significance of single-site and bi-site metastases. All single-site metastases were independent prognostic factors and co-metastases ended up with even worse survival outcomes. Thus, our findings would be beneficial for research design and clinical practice.
The study indicates that integrated 125I seed stents are effective in reducing jaundice symptoms, inhibiting tumor growth, improving stent patency and prolonging patient survival, which may serve as a safer and more feasible method in treating malignant lower biliary obstruction with minimal invasiveness.
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