Ferroptosis is a novel type of regulated cell death, whose unique metabolic characteristics are commonly used to evaluate the conditions of various diseases especially in tumors. Accumulating evidence supports that ferroptosis can regulate tumor development, metastasis, and therapeutic responses. Considering to the important role of chemotherapy in tumor treatment, drug resistance has become the most serious challenge. Revealing the molecular mechanism of ferroptosis is expected to solve tumor drug resistance and find new therapies to treat cancers. In this review, we discuss the relationship between ferroptosis and tumor drug resistance, summarize the abnormal ferroptosis in tissues of different cancer types and current research progress and challenges in overcoming treatment resistance, and explore the concept of targeting ferroptosis to improve tumor treatment outcomes.

Background: Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. We also investigate the functions of some specific exosome biomarkers in the progression of CRPC. Methods: Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models. Results: Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. Conclusion: Integration of proteomics and metabolomics data generated proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression.

Human bladder cancer is one of the common malignant tumors, and it mainly occurs in men. miR-182-5p, a member of miR-183 family, acts as tumor suppressor or oncogene in various kinds of tumors. In this study, we first investigate that the absence of miR-182-5p in human bladder cancer promotes tumor growth by regulating the expression of Cofilin 1, an actin modulating-protein. Human bladder tumor tissue specimens were collected to detect the expression of miR-182-5p and Cofilin 1 by qRT-PCR. Luciferase activity assay was performed to demonstrate the regulation of Cofilin 1 mRNA 3′UTR by miR-182-5p. Then, cell experiments were performed to analysis the effect of miR-182-5p/Cofilin 1 pathway on tumor cell proliferation, migration, invasion and colony forming efficiency. Finally, xenograft tumor models were established to evaluate the role of miR-182-5p in tumorigenesis abilities in vivo. qRT-PCR and Western blotting analysis showed that Cofilin 1 expression was up-regulated in both bladder cancer tissues and cell lines compared with normal. Luciferase activity assay showed that miR-182-5p specifically targets Cofilin 1 mRNA 3′UTR and represses the expression of Cofilin 1. Also, miR-182-5p inhibited bladder tumor cell proliferation, migration, invasion and colony forming efficiency. Furthermore, xenograft tumor model assay showed that miR-182-5p plays a negative role in bladder cancer tumorigenesis abilities in vivo. Present results suggest that miR-182-5p could inhibit human bladder tumor growth by repressing Cofilin 1 expression. Our findings may provide a new horizon for exploring therapeutic target of bladder cancer.

Background. Prostate cancer (PCa) is a malignant tumor in males, with a majority of the cases advancing to metastatic castration resistance. Metastasis is the leading cause of mortality in PCa. The traditional early detection and prediction approaches cannot differentiate between the different stages of PCa. Therefore, new biomarkers are necessary for early detection and clear differentiation of PCa stages to provide precise therapeutic intervention. Methods. The objective of the study was to find significant differences in genes and combine the three GEO datasets with TCGA-PRAD datasets (DEG). Weighted gene coexpression network analysis (WGCNA) determined the gene set and PCa clinical feature correlation module utilizing the TGGA-PRAD clinical feature data. The correlation module genes were rescreened using the biological information analysis tools, with the three hub genes (TOP2A, NCAPG, and BUB1B) for proper verification. Finally, internal (TCGA) and external (GSE32571, GSE70770) validation datasets were used to validate and predict the value of last hub genes. Results. The hub gene was abnormally upregulated in PCa samples during verification. The expression of each gene was favorably connected with the Gleason score and TN tumor grade in clinical samples but negatively correlated with the overall survival rate. The expression of these genes was linked to CD8 naive cells and macrophages, among other cells. Antitumor immune cells like NK and NKT were favorably and adversely correlated with infiltrating cells, respectively. Simultaneously, the GSCV and GSEA indicated that the hub gene is connected with cell proliferation, death, and androgen receptor, among other signaling pathways. Therefore, these genes could influence the incidence and progression of PCa by participating in or modulating various signaling pathways. Furthermore, using the online tool of CMap, we examined the individual medications for Hughes and determined that tipifarnib could be useful for the clinical therapy of PCa. Conclusion. TOP2A, NCAPG, and BUB1B are important genes intimately linked to the clinical prognosis of PCa and can be employed as reliable biomarkers for early diagnosis and prognosis. Moreover, these genes can provide a theoretical basis for precision differentiation and treatment of PCa.

Inguinal lymph node metastases significantly impact the prognosis of patients with penile cancer. Therefore, timely inguinal lymph node dissection is essential for the comprehensive treatment of penile cancer. Compared with the traditional open inguinal lymphadenectomy, laparoscopic inguinal lymphadenectomy offers similar tumor control with fewer complications. The current techniques for the laparoscopic surgical approach include L-lymphoid clearance sequence and preservation of the great saphenous vein. In this study, a transabdominal subcutaneous anterograde approach was employed to improve laparoscopic inguinal lymph node dissection and conserve the great saphenous vein, resulting in favorable outcomes. Furthermore, only 2 out of 21 patients experienced wound infections, and only 1 exhibited lymphatic leakage from the drainage orifice. These findings indicate that the use of an innovative subcutaneous transperitoneal retrograde approach is safe for abdominal endoscopic common iliac plexus dissection with fewer complications in patients with penile cancer compared with traditional open surgery. Notably, the postoperative survival rate of penile cancer patients is significantly influenced by the presence or absence of inguinal lymph node metastasis and the extent of metastasis. Timely inguinal lymph node dissection is essential since it significantly impacts the treatment of penile cancer. Besides, laparoscopic inguinal lymphadenectomy offers comparable tumor control to open surgery with significantly reduced complications. Notably, standardized approaches for laparoscopic surgery, cleaning procedures, and preservation of the saphenous vein are crucial for inguinal lymph node dissection. The laparoscopic inguinal lymphadenectomy technique can be improved by employing the abdominal subcutaneous anterograde approach. This article provides a comprehensive account of the procedures and technical improvements associated with the modified laparoscopic inguinal lymphadenectomy using the abdominal subcutaneous approach.