CircUGGT2 facilitates progression and cisplatin resistance of bladder cancer through nonhomologous end-joining pathway.

The development of resistance to cisplatin (CDDP) in bladder cancer presents a notable obstacle, with indications pointing to the substantial role of circular RNAs (circRNAs) in this resistance. Nevertheless, the precise mechanisms through which circRNAs govern resistance are not yet fully understood. Our findings demonstrate that circUGGT2 is significantly upregulated in bladder cancer, facilitating cancer cell migration and invasion. Additionally, our analysis of eighty patient outcomes revealed a negative correlation between circUGGT2 expression levels and prognosis. Using circRNA pull-down assays, mass spectrometry analyses, and RNA Immunoprecipitation (RIP), it was shown that circUGGT2 interacts with the KU heterodimer, consisting of KU70 and KU80. Both KU70 and KU80 are critical components of the non-homologous end joining (NHEJ) pathway, which plays a role in CDDP resistance. Flow cytometry was utilized in this study to illustrate the impact of circUGGT2 on the sensitivity of bladder cancer cell lines to CDDP through its interaction with KU70 and KU80. Additionally, a reduction in the levels of DNA repair factors associated with the NHEJ pathway, such as KU70, KU80, DNA-PKcs, and XRCC4, was observed in chromatin of bladder cancer cells following circUGGT2 knockdown post-CDDP treatment, while the levels of DNA repair factors in total cellular proteins remained constant. Thus, the promotion of CDDP resistance by circUGGT2 is attributed to its facilitation of repair factor recruitment to DNA breaks via interaction with the KU heterodimer. Furthermore, our study demonstrated that knockdown of circUGGT2 resulted in reduced levels of γH2AX, a marker of DNA damage response, in CDDP-treated bladder cancer cells, implicating circUGGT2 in the NHEJ pathway for DNA repair.

Association of tumor budding with clinicopathological features and prognostic value in stage III-IV colorectal cancer.

BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.

Partial response to pralsetinib in an advanced pulmonary sarcomatoid carcinoma patient harboring a KIF5B-RET rearrangement: a case report.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a rare and unconventional non-small-cell lung cancer (NSCLC) that appears to be aggressive, with a poor prognosis and response to conventional treatment. Approximately 30% of PSCs have potentially targetable genomic alterations, but few studies have involved RET gene fusions, and corresponding targeted therapies are lacking. CASE PRESENTATION: In this report, we describe a patient with PSC harboring a KIF5B-RET gene fusion who was initially diagnosed with stage IVb lung cancer. Due to the poor performance status, the patient was unable to tolerate any radiotherapy or chemotherapy. Based on the next-generation sequencing (NGS) result of RET gene fusion, the patient was treated with pralsetinib. Two months after the treatment, the patient achieved a partial response. CONCLUSIONS: Our case indicates that RET is one of the main driver oncogenes of PSC and provides useful information for precise RET inhibitor administration in the future. Thus, the use of comprehensive genomic profiling may provide important treatment options for PSC.

Case report and literature review: Malignant adenomyoepithelioma after breast augmentation.

Background: Breast malignant adenomyoepithelioma (MAME) after breast augmentation has never been reported. Case summary: We reported a case of a 55-year-old woman who was diagnosed with breast MAME 16 years after breast augmentation. Breast augmentation was performed on the patient with two 200 ml round textured prostheses in the subpectoral plane through axillary incisions in 2004. However, a breast ultrasound in 2020 revealed a suspicious malignant lump in the right breast, which was finally confirmed as MAME by pathology. Skin-sparing modified radical mastectomy and immediate breast reconstruction with expander implantation were performed. Subsequently, the patient received three cycles of chemotherapy with the regimen of anthracycline and cyclophosphamide. In the following nearly 2 years of follow-up, no tumor recurrence and metastasis were found, and the overall treatment was satisfactory for the patient. Conclusion: Here, we present a unique case in which a patient was diagnosed with breast MAME after breast augmentation. Skin-sparing modified radical mastectomy and immediate breast reconstruction with expander implantation are feasible approaches that yield at least short-term oncological safety and acceptable aesthetic results. However, whether there is a potential relationship between MAME and breast implants remains to be further explored. Meanwhile, due to the rarity of breast MAME, more authoritative strategies considering both oncological safety and aesthetics to seek better long-term therapeutic effects are needed.

Identification of ISG15 and ZFP36 as novel hypoxia- and immune-related gene signatures contributing to a new perspective for the treatment of prostate cancer by bioinformatics and experimental verification.

BACKGROUND: Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients. METHODS: The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays. RESULTS: A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells. CONCLUSION: Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa.