Hormones and Cancer最新文献

Background

Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients.

Methods

CC patients’ relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm.

Results

Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746–0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine.

Conclusions

An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.

Introduction

Surgery for gliomas involving eloquent areas is a very challenging microsurgical procedure. Maximizing both the extent of resection (EOR) and preservation of neurological function have always been the focus of attention. Intraoperative neurophysiological monitoring (IONM) is widely used in this kind of surgery. The purpose of this study was to evaluate the efficacy of IONM in eloquent area glioma surgery.

Methods

Sixty-eight glioma patients who underwent surgical treatment from 2014 to 2019 were included in this retrospective cohort study, which focused on eloquent areas. Clinical indicators and IONM data were analysed preoperatively, two weeks after surgery, and at the final follow-up. Logistic regression, Cox regression, and Kaplan‒Meier analyses were performed, and nomograms were then established for predicting prognosis. The diagnostic value of the IONM indicator was evaluated by the receiver operating characteristic (ROC) curve.

Results

IONM had no effect on the postoperative outcomes, including EOR, intraoperative bleeding volume, duration of surgery, length of hospital stay, and neurological function status. However, at the three-month follow-up, the percentage of patients who had deteriorated function in the monitored group was significantly lower than that in the unmonitored group (23.3% vs. 52.6%; P < 0.05). Logistic regression analysis showed that IONM was a significant factor in long-term neurological function (OR = 0.23, 95% CI (0.07–0.70). In the survival analysis, long-term neurological deterioration indicated worsened overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was established through Cox regression model analysis, which could predict the probability 3-year survival rate. The concordance index was 0.761 (95% CI 0.734–0.788). The sensitivity and specificity of IONM evoked potential (SSEP and TCeMEP) were 0.875 and 0.909, respectively. In the ROC curve analysis, the area under the curve (AUC) for the SSEP and TCeMEP curves was 0.892 (P < 0.05).

Conclusions

The application of IONM could improve long-term neurological function, which is closely related to prognosis and can be used as an independent prognostic factor. IONM is practical and widely available for predicting postoperative functional deficits in patients with eloquent area glioma.

Background

Circulating tumor cell (CTC) detection is one form of liquid biopsy. It is a novel technique that is beginning to be applied in the field of thyroid cancer. The present study was designed to evaluate the diagnostic value of CTCs in patients with thyroid cancer.

Methods

A total of 1478 patients were retrospectively analyzed and divided into malignant group (n = 747) and benign group (n = 731). Peripheral blood was collected, and CTCs were enriched and quantified before surgery. The baseline data of the two groups were matched by Propensity Score Matching (PSM). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of different indicators for thyroid cancer. The malignant group before PSM was further divided into subgroups according to the BRAF V600E mutation and lymphatic metastasis (N stage), and the number of CTCs in different subgroups was compared.

Results

After 1:1 PSM, baseline characteristics of the malignant group and benign group were matched and assigned 315 cases in each group. The number of CTCs and the TPOAb values were comparable in the two groups (p > 0.05). The TgAb values [1.890 (1.110 – 16.010) vs 1.645 (1.030 – 7.073) IU/mL, p = 0.049] were significantly higher in the malignant group than in the benign group. After PSM, ROC analyses showed that the areas under the curve (AUCs) of CTC, TgAb and ultrasound were 0.537 (sensitivity 65.6%, specificity 45.8%), 0.546 (sensitivity 40.0%, specificity 70.8%) and 0.705 (sensitivity 77.1%, specificity 63.2%), respectively. The AUCs of the combined detection of ‘CTC + ultrasound’ (combine 1) and the combined detection of ‘CTC + TgAb + ultrasound’ (combine 2) were 0.718 (sensitivity 79.3%, specificity 61.7%) and 0.724 (sensitivity 78.0%, specificity 63.3%), respectively. The AUC of ultrasound was significantly higher than CTC (p < 0.001). There was no statistically significant difference in AUC between combination 1 and ultrasound, and between combination 2 and ultrasound (p > 0.05). The number of CTCs between the N0 and N1 subgroups, and between the BRAF mutant and BRAF wild subgroups was comparable (p > 0.05).

Conclusions

As an emerging and noninvasive testing tool, the efficacy of CTCs in diagnosing thyroid cancer is limited.

Background

Bilateral suprarenal neuroblastoma (BSN) is a rare presentation. Few previously published literature showed BSN patients to have favorable pattern and prognosis. This study aim was to evaluate clinical and biological features in relation to outcome of Egyptian patients with BSN.

Methods

Included patients were diagnosed from 2007 to 2017, retrospectively. Tissue biopsy, imaging and bone marrow were evaluated at presentation. Clinical, demographic, biological variables and risk group were determined and analyzed in relation to overall (OS) and event-free-survival (EFS).

Results

BSN patients (n = 33) represented 2% of hospital patients with neuroblastoma during the 10-year study period, 17 were males and 16 were females. Twenty-four patients (72.7%) were infants, and 9 patients (27.3%) were above 1 year of age (range: 1 month to 3 years). Metachronous disease was present in only one patient. Amplified MYCN was found in 10 patients. Initially, most patients (n = 25) had distant metastasis, 6 had stage 3 versus 2 stage 2. Fifteen were high risk (HR), 15 intermediate (IR), 1 low risk (LR) and 2 were undetermined due to inadequate tissue biopsy. Three-year OS for HR and IR patients were 40.5% and 83.9% versus 23.2% and 56.6% EFS; respectively.

Conclusion

BSN treatment is similar to unilateral disease. A more conservative surgical approach with adrenal tissue preservation on less extensive side should be considered. Biological variables and extent of disease are amongst the most important prognostic determinants. Future studies are warranted to further address the biologic profiling of BSN and highlight prognostic significance of size difference between both adrenal sides.

Background

Cuproptosis induces proteotoxic stress and eventually leads to cell death. However, the relationship between cuproptosis and lncRNAs in cervical cancer has not been fully elucidated. Therefore, we aim to explore the association among lncRNAs, cuproptosis and clinical features in cervical cancer.

Methods

RNA sequencing, genetic mutations, and clinical data of CESC patients were obtained from TCGA. Cuproptosis-associated genes were gathered. WGCNA was used to cluster important modules, and KEGG, GO, GSEA and GSVA were used to explore functional and pathway enrichment. The association between immune microenvironment and cuproptosis-related lncRNAs was performed by using cibersort algorithm and other platforms, including XCELL, TIMER, QUANTISEQ, MCPCOUNTER and EPIC. Fluorescence quantitative PCR was employed to detect the expression of LINC01833 and LINC02321, and CCK-8 and cell scratch assays were used to assess cell proliferation and migration capabilities after LINCRNA interference.

Results

202 upregulated and 45 downregulated lncRNAs were selected. The survival analysis showed that there was a statistically significant difference in survival rates between the high-risk and low-risk groups. The prognosis of tumour mutation burden and the degree of immune infiltration were differed noticeably between the high-risk and low-risk groups. BHG712, TL-2-105, FR-180204, Masitinib, TAK-715, ODI-027, JW-7-24-2, and OSI-930 had substantially higher IC50 values in the high-risk group. Notably, we found AL360178.1 was associated with RNF44 E3 ubiquitin ligase expression. In cervical cancer cell lines, LINC01833 and LINC02321 displayed significant upregulation. Efficient siRNA transfection led to a decreased expression of LINC01833 and LINC02321. This knockdown significantly hindered both cell proliferation and migration capabilities in cervical cancer cells compared to the negative control.

Conclusion

In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer.

Objective

Triple-negative breast cancer (TNBC) represents a particularly aggressive form of breast cancer with a poor prognosis due to a lack of targeted treatments resulting from limited a understanding of the underlying mechanisms. The aim of this study was the identification of hub genes for TNBC and assess their clinical applicability in predicting the disease.

Methods

This study employed a combination of weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify new susceptible modules and central genes in TNBC. The potential functional roles of the central genes were investigated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Furthermore, a predictive model and ROC curve were developed to assess the diagnostic performance of the identified central genes. The correlation between CCNB1 and immune cells proportion was also investigated. At last, a Mendelian randomization (MR) analysis utilizing Genome-Wide Association Study (GWAS) data was analyzed to establish the causal effect of CCNB1 level on TNBC.

Results

WGCNA was applied to determine gene co-expression maps and identify the most relevant module. Through a screening process, 1585 candidate hub genes were subsequently identified with WGCNA and DEGs. GO and KEGG function enrichment analysis indicated that these core genes were related to various biological processes, such as organelle fission, chromosome segregation, nuclear division, mitotic cell cycle phase transition, the cell cycle, amyotrophic lateral sclerosis, and motor proteins. Using STRING and Cytoscape, the top five genes with high degrees were identified as CDC2, CCNB1, CCNA2, TOP2A, and CCNB2. The nomogram model demonstrated good performance in predicting TNBC risk and was proven effective in diagnosis, as evidenced by the receiver operating characteristic (ROC) curve. Further investigation revealed a causal association between CCNB1 and immune cell infiltrates in TNBC. Survival analysis revealed high expression of the CCNB1 gene leads to poorer prognosis in TNBC patients. Additionally, analysis using inverse variance weighting revealed that CCNB1 was linked to a 2.8% higher risk of TNBC (OR: 1.028, 95% CI 1.002–1.055, p = 0.032).

Conclusion

We established a co-expression network using the WGCNA methodology to detect pivotal genes associated with TNBC. This finding holds promise for advancing the creation of pre-symptomatic diagnostic tools and deepening our comprehension of the pathogenic mechanisms involved in TNBC risk genes.

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer—which are believed to be connected to the malfunction of multigene and multilevel cell signaling network—remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

Background

Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC).

Methods

Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored.

Results

A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan–Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model’s accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8⁺ T cells, CD4⁺ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry.

Conclusion

This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Purpose

The purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer.

Methods

RT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan–Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays.

Results

It was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer.

Conclusion

DSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

Objective

Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ.

Methods

Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed.

Results

The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages.

Conclusion

In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.