Background:Cuproptosis-related gene and long non-coding RNA (lncRNA) modulation of cancer regulation is well-established. This investigation aimed to elucidate the prognostic implications of cuproptosis-associated lncRNAs in muscle-invasive bladder cancer (MIBC). Methods:Employing the Cancer Genome Atlas (TCGA) and IMvigor210 cohorts, bioinformatics and statistical analyses probed the prognostic relevance of cuproptosis-related lncRNAs. Results:Co-expression analysis revealed tight associations between lncRNA expression and cuproptosis-linked genes, with 13 cuproptosis-related lncRNAs found to correlate with MIBC prognosis. Lasso regression identified a six-lncRNA prognostic signature, enabling patient stratification into high- and low-risk categories. Tissue validation substantiated differential expression of FAM13A-AS1, GHRLOS, LINC00456, OPA1-AS1, RAP2C-AS1, and UBE2Q1-AS1 between MIBC tumor and normal tissues. Comparative analyses of tumor microenvironments and immune profiles between risk groups disclosed elevated immunosuppressive molecule expression, including programmed cell death-1 (PD-L1) and T-cell immunoglobulin-3 (TIM-3), in high-risk individuals. Conclusion:These findings suggest that cuproptosis-related lncRNAs may modulate the expression of immunosuppressive molecules, thereby influencing MIBC tumorigenesis and progression. Further exploration is warranted to unveil novel therapeutic targets for MIBC based on the expression patterns of cuproptosis-related lncRNAs and their impact on immune responses in the tumor microenvironment.

Abstract The high recurrence rate of non-muscle invasive bladder cancer (NMIBC) is a non-negligible problem in a clinical setting. Therefore, it is important to explore the affecting factors and to identify promising biological indicators that could predict the recurrence hazard. The present study employed a CIBERSORT computational method to characterize the immune cell infiltration (ICI) landscape using 549 NMIBC cases from the training cohort. Three ICI phenotypes were characterized and differentially expressed genes (DEGs) were identified and evaluated using Cox regression analysis and protein-protein interaction network construction. A four-gene signature for prognostic prediction in NMIBC patients was ultimately established, which was further evaluated by Kaplan-Meier analysis, revealing a significant recurrence-free survival (RFS) difference. The signature was constructed to stratify NMIBC patients into high- and low-risk groups. For patients in the high-risk group, significantly reduced RFS was observed when compared to patients in the low-risk group. Tissue validation results also showed that CDC20, CPL3A1, PLK1, and FOXM1 were differentially expressed between tumor and normal tissues from NMIBC patients. Results of the receiver operating characteristic curve (ROC) analysis demonstrated that the signature had a significant predictive power for NMIBC recurrence. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature manifested close interactions with cell-cycle pathways and tumor environment. In conclusion, this novel cell cycle-related four-gene signature can be used for prognostic prediction in NMIBC.

Abstract The high recurrence rate of non-muscle invasive bladder cancer (NMIBC) is a non-negligible problem in a clinical setting. Therefore, it is important to explore the affecting factors and to identify promising biological indicators that could predict the recurrence hazard. The present study employed a CIBERSORT computational method to characterize the immune cell infiltration (ICI) landscape using 549 NMIBC cases from the training cohort. Three ICI phenotypes were characterized and differentially expressed genes (DEGs) were identified and evaluated using Cox regression analysis and protein-protein interaction network construction. A four-gene signature for prognostic prediction in NMIBC patients was ultimately established, which was further evaluated by Kaplan-Meier analysis, revealing a significant recurrence-free survival (RFS) difference. The signature was constructed to stratify NMIBC patients into high- and low-risk groups. For patients in the high-risk group, significantly reduced RFS was observed when compared to patients in the low-risk group. Tissue validation results also showed that CDC20, CPL3A1, PLK1, and FOXM1 were differentially expressed between tumor and normal tissues from NMIBC patients. Results of the receiver operating characteristic curve (ROC) analysis demonstrated that the signature had a significant predictive power for NMIBC recurrence. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature manifested close interactions with cell-cycle pathways and tumor environment. In conclusion, this novel cell cycle-related four-gene signature can be used for prognostic prediction in NMIBC.

Monitoring of cerebrospinal fluid (CSF) microRNAs (miRs) offers a promising option for the diagnosis and management of patients with central nervous system tumors. However, the sensitive detection of miRs in clinical CSF samples has been hindered by the ultra-low abundance of target miRs. Here, we report an electrochemical biosensor for the highly sensitive label-free detection of CSF miR-21 relying on target-induced redox signal amplification (eTIRSA). The biosensor was developed by covalently assembling the capture stands partially complementary to miR-21 on the gold nanoparticle-coated glassy carbon electrode. In the presence of miR-21, the short capture stand hybridized with the partial bases of miR-21, allowing the rest sequence of the target molecule to further bind with a long guanine-rich sequence which could specifically adsorb a number of methylene blue indicators, thus generating an amplified electrochemical redox signal, typically at a working potential of − 0.19 V (vs. SCE). The response of the surface-bound methylene blue indicators was positively correlated to the concentration of miR-21, providing a dynamic range of 0.5–80 pM and a limit of detection down to 56 fM. Moreover, the eTIRSA biosensor had high specificity with single-base resolution and exhibited good performance for label-free quantification of miR-21 in medulloblastoma cell extracts and clinical CSF samples and for accurate discrimination of medulloblastoma against non-cancer controls, indicating its potential application in CSF miR-based liquid biopsy of brain cancers.

Objectives: Bladder cancer (BLCA) is the most common malignant tumor in the urinary system, while the prognosis of muscle-invasive bladder cancer (MIBC) is poor. Cuproptosis might be a promising therapeutic approach to trigger tumor cell death. This study aimed to figure out the role of cuproptosis in BLCA and constructed a new cuproptosis scoring system to guide clinical diagnosis and individualize treatments. Methods: Consensus clustering was used to classify 490 patients with BLCA from TCGA and GEO cohorts. Survival outcomes and functional enrichment analyses were performed between the different subtypes. The cuproptosis scoring system was constructed by LASSO-Cox analysis. ESTIMATE, CIBERSORT, and ssGSEA were used to investigate the tumor microenvironment (TME). Drug sensitivity was evaluated with pRRophetic. An immunotherapy cohort was used to investigate the treatment response. The cuproptosis scoring system was verified in our own cohort with quantitative real-time PCR. Results: An overview of 12 cuproptosis genes (CuGs) in the TCGA database was depicted. Based on the mRNA expression profiles of CuGs, patients were classified into two cuproptosis molecular patterns. Based on the differential genes between the two cuproptosis patterns, the patients were classified into two cuproptosis gene clusters. There were distinct survival outcomes, signaling pathways, and TME between the two subtypes. A 7-gene cuproptosis scoring system was constructed. Patients with high cuproptosis scores showed worse OS and more immunosuppressing TME than those with low cuproptosis scores. The two cuproptosis score groups had distinct mutation profiles. Patients with high cuproptosis scores tended to be sensitive to chemotherapy drugs, but insensitive to immune checkpoint inhibitors (ICIs) treatment. Conclusion: This study depicted the landscape of cuproptosis in BLCA. We constructed a cuproptosis scoring system to predict the prognosis of BLCA patients. There were significant differences in survival outcomes, TME, mutation profiles, and drug sensitivities in high and low cuproptosis score patients. The cuproptosis scoring system could help oncologists comprehensively understand the tumor characteristic of BLCA and make individualized treatment strategies.

Cancer is the leading cause of death in China and a significant public health problem with increasing incidence and fatality rates. The Han nationality is the main ethnic group in China, and many reports on the epidemiology of cancers in Han nationality are published. However no studies report the cancer spectrum of Uygurs which are one of the minority nationalities in China. Hence, we present incidence and mortality numbers of different cancers for the Uygur patients for the period 2018-2020 in Hotan District where Uygur population accounts for 99 %. During the 3-year study period, 2509 new Uygur cancer cases were registered, comprising 774 men and 1735 women. Cervical cancer was the most common, followed by esophageal, breast, gastric and colorectal cancers. The most common cancers in women and men were cervical cancer and esophageal cancer, respectively. In conclusion, the cancer spectrum in Hotan is different from other regions of China and our research revealed the cancer incidence in Hotan, which could help us to take appropriate measures to reduce the incidence rate.

Background. A phase III randomized multicenter trial (ALTER0303) reported anlotinib to be significantly beneficial to patient survival. An array of inflammatory biomarkers, such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), are associated with the response to treatment in numerous types of cancer. However, we found few studies investigating the predictive value of NLR or PLR in advanced NSCLC treatment with anlotinib. Thus, our objective was to examine the relationship between NLR and PLR and treatment effect, as well as to individuate patient stratification and selection. Methods. NLR and PLR as well as their variations were calculated in 152 advanced NSCLC patients receiving anlotinib as a third or further-line treatment at Ningbo Medical Center Lihuili Hospital between July 2018 and December 2020. The best cut-off values of NLR and PLR for predicting the treatment response were selected. Survival curves were plotted using the Kaplan–Meier method, while univariable and multivariable Cox regression were used to identify and determine dependent and independent predictors of survival. Results, Low disease control rate (DCR) was related with a high pre-NLR ( P = 0.007 ), high pre-PLR ( P = 0.004 ), and elevated post-NLR ( P = 0.010 ). Multivariate analysis determined high pre-PLR (>205.63) and elevated post-NLR to be independently associated with poor PFS or OS. Patients whose risk score was 2 resulting from the prediction model based on pre-PLR and post-NLR had a 4.52 times higher risk of death compared to patients whose risk score was 0 (HR: 4.516, 95% CI: 2.502-8.152, P ≤ 0.001 ). Conclusions. Pre-PLR and post-NLR were independent prognostic indicators in patients with advanced NSCLC receiving anlotinib as a third or further-line treatment. Patients whose risk value score was 0 had a higher therapy effectiveness and better survival.

BackgroundAccording to the randomized multicenter phase II trial (ALTER1202), anlotinib has been approved as a third-line therapy for advanced small-cell lung cancer (SCLC). Some studies showed the predictive function of inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in the different cancers treated with anti-vascular targeting drugs. However, none of the studies showed the roles of NLR, PLR, and LMR in SCLC patients receiving anlotinib. Thus, our objective was to establish a scoring system based on inflammation to individuate patient stratification and selection based on NLR, PLR, and LMR. MethodsNLR, PLR, and LMR and their variations were calculated in 53 advanced SCLC patients receiving anlotinib as a third- or further-line treatment at Ningbo Medical Center Lihuili Hospital between January 2019 and December 2021. Kaplan-Meier curves were plotted. Both univariate and multivariate Cox regressions were used to identify predictors of survival. ResultsDisease control rate was related to pre-NLR, pre-PLR, pre-LMR, post-NLR elevation, post-PLR elevation, and post-LMR elevation. The multivariate analysis determined post-NLR elevation, pre-PLR > 240.56, and pre-LMR <= 1.61 to be independently associated with progression-free survival, not overall survival. The inflammation-based prognostic scoring system demonstrated favorable predictive ability from the receiver operating characteristic curve (AUC: 0.791, 95% CI: 0.645-0.938). ConclusionsPost-NLR variation, pre-PLR, and pre-LMR were independent prognostic factors for PFS in advanced SCLC receiving anlotinib monotherapy. The inflammation-based prognostic scoring system can accurately predict effectiveness and survival.

Background: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed. Methods: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. Results: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). Conclusion: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Background Anlotinib, a small molecule for multi-target tyrosine kinase inhibition, is the third or further line of defense for treatment of non-small cell lung cancer (NSCLC). Findings from an ALTER0303 phase III trial revealed that this drug confers significant survival benefits in patients. Although numerous inflammatory biomarkers have been shown to play vital roles in treatment, the clinical significance of blood lipid levels before treatment has not been evaluated. Here, this research aims to explore the relationship between blood lipids and efficacy of anlotinib, with a view of generating insights to guide future development of convenient and individualized treatment therapies. Methods This study analyzed basal blood lipids levels, including triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL), among other variables before treatment, in 137 patients with advanced NSCLC who received anlotinib as third or further-line treatment at the Ningbo Medical Center Lihuili Hospital, between July 2018 and December 2020. We determined the best cut off value for predicting treatment responses, generated survival curves using the Kaplan–Meier method, then applied univariate and multivariate Cox regression analyses to assess predictors of survival. Results The entire study population recorded median progression-free survival (PFS) and overall survival (OS) of 4 (95% CI 3.142–4.858) and 8.3 (95% CI 6.843–9.757) months, respectively. Researchers observed statistically significant differences across subgroups, between blood lipid indexes with different efficacies, except in the HDL subgroup. The low disease control rate (DCR) was associated with significantly elevated TG, TC and LDL levels ( P = 0.000). Multivariate analysis demonstrated that elevated TC and LDL levels were independently associated with poor PFS or OS ( P ≤ 0.003). Then, we established a prediction model, and set high TC or high LDL as the risk factor, respectively. There were significant differences in PFS ( p = 0.000) and OS ( p = 0.012) between 0 and ≥ 1 scores. Conclusions Prior to anlotinib therapy, TC and LDL levels, are independent prognostic indicators for patients with advanced NSCLC treated with this drug as a third or further-line treatment option. In addition, a risk score of 0 was attributed to a combination of low TC and low LDL, and these patients were exhibited excellent efficacies and survival rates.

Background: Various inflammatory biomarkers, such as the neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR / PLR and prognosis was also analyzed.Methods: NLR and PLR were calculated in 113 locally advanced ESCC located in middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. Results: NLR and PLR was both associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organs metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of multivariate analysis revealed that NLR (> 2.07) and PLR (> 183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). Conclusions: Low pretreatment NLR patients made a decision to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic target for tumor initiation, migration, proliferation, and chemosensitivity. Thus, therapeutic strategies that focus on targeting Drp1 and its related signaling pathway pave a new way to address the ineffectiveness of traditional cancer therapies. Micheliolide (MCL), a guaianolide sesquiterpene lactone, can selectively eradicate acute myeloid leukemia stem or progenitor cells. But the effect of MCL on the mitochondrial dynamics of cancer cells is still not well demonstrated. In this study, we show that MCL inhibited the growth of MCF-7 human breast cancer cells, accompanied by increased mitochondrial fission and upregulation of Drp1. The results obtained from overexpression experiments of wild or dominant-negative mutant type of Drp1 demonstrate that Drp1 is both necessary and sufficient to induce MDA-MB-231 and MCF-7 cell death. Furthermore, mitochondrial membrane potential decreased, whereas reactive oxygen species (ROS) generation, cytochrome c release, and PARP cleavage were enhanced after overexpression of Drp1 wild type. On the other hand, overexpression of Drp1-K38A (a dominant-negative mutant of Drp1) rescued cells from increased apoptosis, confirming the role of MCL-induced Drp1 in the observed apoptosis. Finally, MCL-induced Drp1-mediated cell death could be reversed by N-acetyl-L-cysteine (the ROS scavenger) in breast cancer cells. Taken together, the present study shows a novel role for Drp1 in MCL-induced breast cancer cell death, potentially through regulation of ROS-mitochondrial apoptotic pathway.