Prognostic value and immunological characteristics of a novel cuproptosis-related long noncoding RNAs risk signature in kidney renal clear cell carcinoma.

Background: Cuproptosis has been found as a novel cell death mode significantly associated with mitochondrial metabolism, which may be significantly associated with the occurrence and growth of tumors. LncRNAs take on critical significance in regulating the development of kidney renal clear cell carcinoma (KIRC), whereas the correlation between cuproptosis-related LncRNAs (CRLs) and KIRC is not clear at present. Therefore, this study built a prognosis signature based on CRLs, which can achieve accurate prediction of the outcome of KIRC patients. Methods: The TCGA database provided the expression profile information and relevant clinical information of KIRC patients. Univariate Cox, Lasso, and multivariate Cox were employed for building a risk signature based on CRLs. Kaplan-Meier (K-M) survival analysis and time-dependent receiver operating characteristic (ROC) curve were employed for the verification and evaluation of the reliability and accuracy of risk signature. Then, qRT-PCR analysis of risk LncRNAs was conducted. Finally, the possible effect of the developed risk signature on the microenvironment for tumor immunization was speculated in accordance with ssGSEA and ESTIMATE algorithms. Results: A prognosis signature composed of APCDD1L-DT, MINCR, AL161782.1, and AC026401.3 was built based on CRLs. As revealed by the results of the K-M survival study, the OS rate and progression-free survival rate of highrisk KIRC patients were lower than those of lowrisk KIRC patients, and the areas under ROC curves of 1, 3, and 5 years were 0.828, 0.780, and 0.794, separately. The results of the immune analysis showed that there were significant differences in the status of immunization and the microenvironment of tumor between groups at low-risk and at high-risk. The qRT-PCR results showed that the relative expression level of MINCR and APCDD1L-DT were higher in 786-O and 769-P tumor cells than in HK-2 cells, which were normal renal tubular epithelial cells. Conclusion: The developed risk signature takes on critical significance in the prediction of the prognosis of patients with KIRC, and it can bring a novel direction for immunotherapy and clinical drug treatment of KIRC. In addition, 4 identified risk LncRNAs (especially APCDD1L-DT and MINCR) can be novel targets for immunotherapy of KIRC patients.

Erdafitinib exerts the anticancer effect on urothelial carcinoma via induction of authophagy.

Erdafitinib has recently been approved for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC). The current study aimed to evaluate whether erdafitinib inhibits the proliferation in UC via inducing authophagy. Our data showed that erdafitinib demonstrated strong toxicity for the T24 and UMUC6 cell lines. Flow cytometry analysis showed that erdafitinib increased the proportion of G0/G1 phase in both T24 and UMUC6 cells. Additionally, Annexin V staining indicated that erdafitinib enhanced the apoptosis of UC cells. Meanwhile, the expression of apoptosis-related proteins was significantly elevated after treatment with erdafitinib. Transwell assay showed that erdafitinib significantly reduced T24 and UMUC6 cell migration and invasion. More importantly, western blot assay showed that erdafitinib induced the expression of autophagy-related proteins. Besides, GFP-LC3 transfection assay and electron microscopy examination showed that erdafitinib could partially diminish 3-methyladenine (3-MA) induced impairment of autophagy in UC cells. In summary, for the first time we showed novel data that erdafitinib inhibited UC cell malignant proliferation via inducing cell autophagy.

Diagnostic Value of Circulating miR-324 for Prostate Cancer.

BACKGROUND: To investigate the diagnostic value of serum miR-324 in patients with prostate cancer (PC). METHODS: Blood samples from 50 patients with prostate cancer, 30 patients with benign prostatic hyperplasia (BPH), and 20 healthy controls were collected and quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between serum miR-324 level and Gleason classification and TNM staging of prostate cancer was analyzed. ROC curve was used to analyze the value of miR-324 in early diagnosis of prostate cancer. RESULTS: The expression of miR-324 in prostate cancer group was significantly higher than that in the BPH group and normal control group (all p < 0.01). Serum miR-324 was associated with the Gleason score and tumor stage (all p < 0.01). Serum miR-324 was positively correlated with PSA (r = 0.673, p = 0.000); ROC curve analysis showed that the area under the ROC curve of miR-324 (all p < 0.01) (AUC) was 0.911 (95% CI: 0.855 - 0.966, p = 0.000). When the relative expression level of miR-324 was 3.35, the sensitivity, specificity, positive predictive value, and negative predictive values were 86.0%, 82.0%, 82.7%, and 85.4%, respectively. CONCLUSIONS: The increased expression of serum miR-324 in patients with prostate cancer may be a potential new biomarker for the diagnosis of prostate cancer, which is helpful for the differentiation between PC and BPH.