6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P<0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95% CI: 1.202-5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.

We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87

Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P < 0.05). However, the decline in hemoglobin, WBC, and neutrophils attenuated by the 12th month (P ≥ 0.05). Aspartate transaminase (AST), Alanine transferase (ALT), total cholesterol (TC), and triglyceride (TG) increased significantly during everolimus treatment (P < 0.05), and these increases persisted throughout the year-long treatment. Hemoglobin decreased significantly more in male patients (− 15 vs − 6, P = 0.010), and AST showed a more significant increase in males (7.0 vs 3.0, P = 0.041). Platelet counts decreased significantly more in younger patients (≤ 30 years old) compared to older patients (− 50 vs − 14, P = 0.020). Everolimus administration in TSC-RAML patients may increase hematologic risks, with male and younger patients potentially exhibiting greater susceptibility to these effects.

Adult pure androgen-secreting adrenal tumors (PASATs) are rarely reported and the malignancy of such tumor are difficult to confirm before surgery. Here we report a PASAT demonstrating extremely 18F-FDG uptake turned out to benign tumor by postoperative pathology examination. A 19-year-old adolescent found a tumor measuring 7.2 cm located in the right adrenal region on enhanced CT during the routine physical examination. Signs of virilization and elevated testosterone and dehydroepiandrosterone (DHEA) were verified during preoperative examination. 18F-FDG PET/CT revealed the tumor had an extremely high 18F-FDG uptake with a SUVmax reaching 42.7, which turned out to be oncocytic adrenocortical adenoma by pathological examination. 18F-FDG PET/CT may be limited in assessing the malignancy of PASAT.

Background: We aimed to demonstrate the function of premelanosome protein (PMEL) as a biomarker to predict the effectiveness of mammalian target of rapamycin complex 1 (mTORC1) inhibitor treatment in renal angiomyolipomas (RAMLs) in tuberous sclerosis complex (TSC) patients. Methods: 95 whole blood samples from 49 patients diagnosed with TSC-RAMLs were collected. PMEL, N4BP2, and PCSK1N expression in the plasma samples were tested by quantitative sandwich ELISA. The target tumor volume assessed by maximum cross-sectional area (CSAmax) in CT scans. Correlation analysis was used to determine the relationship between PMEL expression and target tumors, as well as the tumor reduction rate. Results: The tumor size of TSC-RAMLs positivity correlated with PMEL expression (r = 0.30, p = 0.036) and PCSK1N expression (r = 0.23, p = 0.027), but had no significant relationship with N4BP2 (r = 0.06, p = 0.89). The positive correlation between TSC-RAML tumor volume and PMEL expression still existed in TSC patients before (r = 0.30, p = 0.026) and after mTORC1 inhibitor treatment (r = 0.41, p = 0.0017), but the correlation between tumor volume and PCSK1N expression no longer existed. Further analysis found that PMEL expression negatively correlated with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment (r = −0.50, p = 0.0022), both after 3 months (r = −0.47, p = 0.048) and 6 months of treatment (r = −0.52, p = 0.028). Conclusion: PMEL expression positively correlated with the tumor size of TSC-RAMLs, and inversely with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment, which may suggest that PMEL may serve as a predictive biomarker for the efficacy of mTORC1 inhibitor treatment.

The response to everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML) varies among individuals. This study aims to identify potential factors associated with the response to everolimus. We retrospectively examined data encompassing age, gender, tumor size, computed tomography attenuation value (CT value), CT enhancement, and tumor reduction rate in patients with TSC-RAML undergoing everolimus in two previously registered clinical trials. A total of 33 participants (29.33 ± 6.63 years old, 20 females) were included. The correlation analysis conducted separately for tumors located in the left and right kidneys revealed significant negative correlations (P < 0.05) between tumor reduction rate and age, as well as tumor size. While significant positive correlations (P < 0.05) were observed between tumor reduction rate and unenhanced CT value as well as CT enhancement. Nonetheless, based on multiple linear regression analysis, unenhanced CT value emerged as the sole-independent predictor of tumor reduction rate among age, gender, tumor size, unenhanced CT value and CT enhancement for both left (coefficient = 0.00319, P < 0.0001) and right kidneys (coefficient = 0.00315, P = 0.0104). Notable reductions were observed in unenhanced CT value (− 3.81 vs − 24.70HU, P < 0.0001) and CT enhancement (48.16 vs 33.56HU, P < 0.0001) following a 3-month administration of everolimus. The decline in both unenhanced CT value and tumor size predominantly occurred within the initial 3 months, subsequently maintaining a relatively stable level throughout the treatment. The unenhanced CT value of TSC-RAML showed an independent correlation with the response to everolimus, suggesting its potential as a predictor of everolimus efficacy in patients with TSC-RAML.

Objective:To investigate the effects of preoperative mammalian target of rapamycin(mTOR )inhibitor on partial nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML).Methods:A retrospective analysis was conducted on clinical data from 13 patients who were diagnosed with TSC-RAML and treated at Peking Union Medical College Hospital between August 2019 and July 2022. This cohort included 4 males and 9 females, with ages ranging from 22 to 66 years. All patients underwent partial nephrectomy, with 2 patients requiring two-stage surgeries due to bilateral RAMLs, resulting in a total of 15 surgeries being performed. Preoperative mTOR inhibitors, specifically everolimus (10 mg/d) or sirolimus (2 mg/d), were administered orally for at least 3 months prior to 7 of the surgeries. The effects of mTOR inhibitors on tumor size, tumor computed tomography attenuation value (CT value), and tumor CT enhancement were evaluated. The comparison of surgery-related clinical parameters was conducted between patients who received preoperative mTOR inhibitors and those who did not to assess the influences of mTOR inhibitors on surgery.Results:Compared to the baseline tumor, there was a significant reduction in tumor diameter after mTOR treatment [(6.4±3.1) cm vs. (8.7±3.9)cm], as well as in the CT value in both the unenhanced phase[(-18.63±48.73)HU vs. (-2.13±51.58)HU] and corticomedullary phase[(13.25±64.01)HU vs. (47.25±66.99)HU]. Additionally, tumor CT enhancement also decreased as compared with that before treatment [(31.88±18.20)HU vs. (49.38±20.63)HU]. Patients who received preoperative mTOR inhibitor showed a trend towards shorter operative time for removing per milliliter of tumor compared to those without preoperative mTOR inhibitor [1.06(0.18, 2.40) min/ml vs. 1.98(0.39, 5.03) min/ml] and so was the renal artery clamping time [0.17(0.03, 0.79) min/ml vs. 0.34(0.10, 1.71) min/ml]. Additionally, the amount of intraoperative bleeding for removing per milliliter of tumor was lower in patients with preoperative mTOR inhibitors compared to those without [0.72(0.19, 0.88) ml/ml vs. 1.69(0.59, 4.54) ml/ml].Conclusions:The administration of mTOR inhibitors before partial nephrectomy in patients with TSC-RAM have the potential to reduce tumor size and blood supply, as well as operative time, renal artery clamping time and intraoperative bleeding, which might contribute to surgery safety and preservation of renal function.