Lung adenocarcinoma (LUAD) remains the most common subtype of lung malignancy. Cuproptosis is a newly identified cell death which could regulate tumor cell proliferation and progression. Long non-coding RNAs (lncRNAs) are key molecules and potential biomarkers for diagnosing and treating various diseases. However, the effects of cuproptosis-related lncRNAs on LUAD are still unclear. In our study, 7 cuproptosis-related lncRNAs were selected to establish a prognostic model using univariate Cox regression analysis, LASSO algorithm, and multivariate analysis. Furthermore, we evaluated AC008764.2, AL022323.1, ELN-AS1, and LINC00578, which were identified as protective lncRNAs, while AL031667.3, AL606489.1, and MIR31HG were identified as risk lncRNAs. The risk score calculated by the prognostic model proved to be an effective independent factor compared with other clinical features by Cox regression analyses [univariate analysis: hazard ratio (HR) = 1.065, 95% confidence interval (CI) = 1.043–1.087, P < 0.001; multivariate analysis: HR = 1.067, 95% CI = 1.044–1.091, P < 0.001]. In addition, both analyses (ROC and nomogram) were used to corroborate the accuracy and reliability of this signature. The correlation between cuproptosis-related lncRNAs and immune microenvironment was elucidated, where 7 immune cells and 8 immune-correlated pathways were found to be differentially expressed between two risk groups. Furthermore, our results also identified and verified the ceRNA of cuproptosis-related lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis using bioinformatics tools. MIR31HG was highly expressed in LUAD specimens and some LUAD cell lines. Inhibition of MIR31HG clearly reduced the proliferation, migration, and invasion of the LUAD cells. MIR31HG showed oncogenic features via sponging miR-193a-3p and tended to positively regulate TNFRSF21 expression. In a word, lncRNA MIR31HG acts as an oncogene in LUAD by targeting miR-193a-3p to modulate TNFRSF21, which may be beneficial to the gene therapy of LUAD.
Background A study to evaluate the prevalence of uric acid (UA) nephrolithiasis with dual-energy CT (DECT) and explore the risk factors for kidney stones in primary gout patients. Methods Eighty-four consecutive gout patients underwent urinary tract ultrasonography or DECT to confirm the existence of kidney stones. Urine and blood samples were also taken for laboratory analysis. Results Forty-one subjects (48.8%) had nephrolithiasis diagnosed; 38 had a kidney stone. Thirty-two of the 38 patients underwent a DECT scan, and 27 patients had nephrolithiasis in DECT. Among them, 63.0% (17/27) and 14.8% (4/21) of the patients had pure UA and UA-based mixed stone, respectively, and 22.2% (6/27) had a non-UA stone. Those with nephrolithiasis suffered from more frequent acute attacks and had longer disease durations of gout. At least one urine biochemical abnormality was found in 81% of patients. Forty-four (55.0%) patients presented hypomagnesuria. Forty-three (51.8%) patients had low urine volume. Unduly acidic urine (UAU) was present in 36 patients (44.4%). Hyperuricosuria was only found in ten (12.2%) patients. In comparison to the non-lithiasic group, the lithiasic group was more likely to have a UAU. Binary logistic regression showed that female gender was a protective factor, while disease duration of gout and low urine pH were risk factors for nephrolithiasis. Conclusion Our results indicated that nephrolithiasis, especially UA stones, were more common than previous reports in gout patients indicated, and that disease duration of gout, and low urine pH, were risk factors for nephrolithiasis.
Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.
Bladder cancer (BC) is the most common malignancy of the urinary system. Pyroptosis is a host programmed cell death. However, the effects of pyroptosis-related lncRNAs (PRLs) on BC have not yet been completely elucidated. In this study, a prognostic PRLs model and two ceRNA networks were established using sufficient bioinformatics analysis and preliminary RT-qPCR validation in vitro. 6 PRLs were identified to construct a prognostic model. Then, the prognostic model risk score was verified to be an effective independent factor (Training cohort: Univariate analysis: HR = 1.786, 95% Cl = 1.416-2.252, p < 0.001; multivariate analysis: HR = 1.664, 95% Cl = 1.308-2.116, p < 0.001; testing cohort: Univariate analysis: HR = 1.268, 95% Cl = 1.144-1.405, p < 0.001; multivariate analysis: HR = 1.141, 95% Cl = 1.018-1.280, p = 0.024). Moreover, ROC and nomogram were performed to assess the accuracy of this signature (1-year-AUC = 0.764, 3-years-AUC = 0.769, 5-years-AUC = 0.738). Consequently, we evaluated the survival curves of these 6 lncRNAs using Kaplan–Meier survival analysis, demonstrating that MAFG-DT was risk lncRNA, while OCIAD1-AS1, SLC25A25-AS1, SNHG18, PSMB8-AS1 and TRM31-AS1 were protective lncRNAs. We found a strong correlation between PRLs and tumor immune microenvironment by Pearson’s correlation analysis. As for sensitivity of anti-tumor drugs, the high-risk group was more sensitive to Sorafenib, Bicalutamide and Cisplatin, while the low-risk group was more sensitive to AKT.inhibitor.VIII, Salubrinal and Lenalidomide, etc. Meanwhile, we identified lncRNA OCIAD1-AS1/miR-141-3p/GPM6B and lncRNA OCIAD1-AS1/miR-200a-3p/AKAP11 regulatory axes, which may play a potential role in the progression of BC.
BACKGROUND Gastric cancer is a leading cause of cancer-related mortality worldwide. Many somatic mutations have been identified based on next-generation sequencing; they likely play a vital role in cancer treatment selection. However, next-generation sequencing has not been widely used to diagnose and treat gastric cancer in the clinic. AIM To test the mutant gene frequency as a guide for molecular diagnosis and personalized therapy in gastric cancer by use of next-generation sequencing. METHODS We constructed a panel of 24 mutant genes to detect somatic nucleotide variations and copy number variations based on a next-generation sequencing technique. Our custom panel included high-mutation frequency cancer driver and tumour suppressor genes. Mutated genes were also analyzed using the cBioPortal database. The clinical annotation of important variant mutation sites was evaluated in the ClinVar database. We searched for candidate drugs for targeted therapy and immunotherapy from the OncoKB database. RESULTS In our study, the top 16 frequently mutated genes were TP53(58%), ERBB2(28%), BRCA2 (23%), NF1 (19%), PIK3CA (14%), ATR (14%), MSH2 (12%), FBXW7 (12%), BMPR1A (12%), ERBB3 (11%), ATM (9%), FGFR2 (8%), MET (8%), PTEN (6%), CHD4 (6%), and KRAS (5%). TP53 is a commonly mutated gene in gastric cancer and has a similar frequency to that in the cBioPortal database. 33 gastric cancer patients (51.6%) with microsatellite stability and eight patients (12.5%) with microsatellite instability-high were investigated. Enrichment analyses demonstrated that high-frequency mutated genes had transmembrane receptor protein kinase activity. We discovered that BRCA2, PIK3CA, and FGFR2 gene mutations represent promising biomarkers in gastric cancer. CONCLUSION We developed a powerful panel of 24 genes with high frequencies of mutation that could detect common somatic mutations. The observed mutations provide potential targets for the clinical treatment of gastric cancer.
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