Diagnosis of ccRCC
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S100A2 promotes clear cell renal cell carcinoma tumor metastasis through regulating GLUT2 expression
Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cancer and is highly malignant. Despite advances in diagnostics and treatment, the prognosis for ccRCC remains poor. The dual nature (promotion or inhibition) of S100A2 in different cancer types shows the complex involvement of its tumorigenesis, but its effect in ccRCC remains unclear. In this study, we first elucidate the tumor-promoting function of S100A2 in ccRCC by reprogramming glycolysis. Mechanistically, we demonstrate that S100A2 accelerates cancer progression through its interaction with the transcription factor HNF1A, leading to activating GLUT2 transcription. The upregulation of GLUT2 significantly enhances glucose uptake by cancer cells, thereby fueling augmented glucose metabolism and fostering the malignant progression of ccRCC. Collectively, our findings highlight the pivotal role of the S100A2-HNF1A-GLUT2 axis in promoting migration and invasion of ccRCC by amplifying glycolysis and suggest that targeting the S100A2-HNF1A-GLUT2 axis is clinically relevant for the treatment of metastatic ccRCC.
STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and ferroptosis
Axitinib resistance remains a serious challenge in the treatment of advanced renal cell carcinoma (RCC), and the underlying mechanisms are not fully understood. Here, we constructed an in vivo axitinib-resistant RCC model and identified the long non-coding RNA STX17-DT as a driver of therapy resistance in RCC. The expression of STX17-DT was significantly elevated in axitinib-resistant RCC cells and correlated with poorer prognosis in RCC patients. Elevated levels of STX17-DT contributed to the development of resistance to axitinib both in vitro and in vivo. Mechanistically, STX17-DT modulated the stability of IFI6 mRNA by recruiting and binding to hnRNPA1, leading to decreased accumulation of mitochondrial reactive oxygen species (ROS) and attenuated ferroptosis. Meanwhile, STX17-DT was packaged into extracellular vesicles through hnRNPA1, thus transmitting axitinib resistance to other cells. Compared with axitinib monotherapy, combined treatment of axitinib and STX17-DT-targeted in vivo siRNA demonstrated enhanced therapeutic efficacy. These findings indicate a novel molecular mechanism of axitinib resistance in RCC and suggest that STX17-DT may serve as a prognostic indicator and potential therapeutic target to overcome resistance to targeted therapy.
A UK population-based case-control study of blood tests before cancer diagnosis in patients with non-specific abdominal symptoms
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Prognostic relevance of the neurological symptom burden in brain metastases from breast cancer
Existing prognostic models for breast cancer (BC) brain metastases (BM) overlook neurological symptoms. Thus, we explored the incidence and prognostic relevance of neurological symptoms in a real-world cohort of BC patients with BM.
Long term follow-up of women treated for screen detected atypical ductal hyperplasia or lobular neoplasia in a large UK screening centre
Atypical ductal hyperplasia (ADH) and lobular neoplasia (LN) increase subsequent breast cancer (BC) risk. However, optimal surveillance and risk reduction regimes remain uncertain. We report management and outcomes of women with ADH and LN to provide data on potential screening/prevention strategies.
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