American journal of cancer research最新文献

Background: Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. The crosstalk between tumor tissue and adjacent adipose tissue has been appreciated recently. This study examines the predictive usefulness of brown adipocyte-related genes (BARGs) in ccRCC.

Methods: The transcriptome and clinical data of ccRCC patients were obtained from TCGA-KIRC and USA-ccRCC cohorts (848 tumor samples; 72 normal samples). Lasso-Cox methods were used to construct the risk prognostic signature model. We used Kaplan-Meier survival analysis to evaluate the prognostic significance of the risk model with ROC curves ascertaining prediction accuracy. The differences in immune cell infiltrates and signature risk scores between different risk categories were analyzed. Finally, biological experiments were performed to explore the functions of candidate genes.

Results: TCGA-KIRC patients were classified into two clusters that differed significantly regarding overall survival (OS) and tumor microenvironment. After screening BARGs candidates, a signature consisting of PPP1R1A, DPYSL3, and PTPRM was created to calculate risk score. Patients were assigned to the high or low-risk group, and the high-risk group had a significantly worse prognosis. Consistent trend was validated in external USA-ccRCC cohort. Meanwhile, the signature risk score affected immune cell infiltrates within the ccRCC microenvironment, positively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, CD56^dim, CD56^bright NK cells, MDSCs, and macrophage cells, while negatively correlated with neutrophil, iDCs, mast cells, and eosinophil. Finally, knockdown of PPP1R1A and DPYSL3 in renal cancer cells showed impairment in tumor proliferation ability of ccRCC in vitro and in vivo. Conversely, knockdown of PTPRM exhibited a promotive effect.

Conclusion: We developed a predictive BARGs-related risk signature for early diagnosis and classifying ccRCC patients, which offers potential targets for individualized treatment of ccRCC.

Although immune checkpoint blockade therapy (ICBT) has revolutionized cancer treatment with good therapeutic response in a number of human cancers, including bladder cancer, many cancers still do not respond to ICBT. Analyzing genetic signatures helps the understanding of underlying biological mechanisms. Here, based on two cohorts of bladder cancer patients receiving ICBT, we identified three novel ICBT-associated signatures in the bladder cancer microenvironment, involving genomic stability, angiogenesis and RNA regulatory, which affect PD-L1 expression and patient response to ICBT. The combinations of these signatures with TMB or PD-L1 expression improved the overall survival prediction efficiency over TMB and PD-L1 expression alone for patients receiving ICBT. Moreover, we utilized two methods to search potential drugs or small-molecules that have an impact on ICBT-associated signatures. This study provides new molecular insight into ICBT response of bladder cancer and has the potential to improve the prediction accuracy for patients to benefit from ICBT.

Glioblastoma (GBM) is the most malignant brain tumor frequently characterized by a hypoxic microenvironment. In this investigation, we unveiled unprecedented role of Ribonuclease 4 (RNASE4) in GBM pathogenesis through integrative methodologies. Leveraging The Cancer Genome Atlas (TCGA) dataset and clinical specimens from normal brain tissues, low- and high-grade gliomas, alongside rigorous in vitro and in vivo functional analyses, we identified a consistent upregulation of RNASE4 correlating with advanced GBM pathological stages and poor clinical survival outcomes. Functional assays corroborated the pivotal influences of RNASE4 on key tumorigenic processes such as cell proliferation, migration, invasion, stemness properties and temozolomide (TMZ) resistance. Further, Gene Set Enrichment Analysis (GSEA) illuminated the involvement of RNASE4 in modulating epithelial-mesenchymal transition (EMT) via activation of AXL, AKT and NF-κB signaling pathways. Furthermore, recombinant human RNASE4 (hRNASE4)-mediated NF-κB activation through IκBα phosphorylation and degradation could result in the upregulation of inhibitors of apoptosis proteins (IAPs), such as cIAP1, cIAP2, and SURVIVIN. Notably, treating RNASE4-induced TMZ-resistant cells with the SURVIVIN inhibitor YM-155 significantly restored cellular sensitivity to TMZ therapy. Herein, this study positions RNASE4 as a potent prognostic biomarker and therapeutic target, offering new insights into molecular pathogenesis of GBM and new avenues for future therapeutic interventions.

Pancreatic ductal adenocarcinoma (PDAC) patients' express higher levels of the orphan Nuclear Receptor 4A2 (NR4A2, NURR1) compared to normal pancreas and NR4A2 is a prognostic factor for patient survival. Knockdown of NR4A2 by RNA interference (RNAi) inhibited cell proliferation, invasion, and migration. RNA sequencing performed in NR4A2^(+/+) and NR4A2^(-/-) MiaPaCa2 cells demonstrated that NR4A2 played a significant role in cellular metabolism. Human antigen R (HuR) and isocitrate dehydrogenase 1 (IDH1) were identified as NR4A2 target genes. HuR is a pro-oncogenic RNA binding protein and silencing of HuR by RNAi significantly downregulated expression of NR4A2. Expression of HuR and IDH1 were significantly downregulated after treatment with NR4A2 inverse agonist, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane resulting in significant inhibition of tumor growth in an athymic nude mouse xenograft model. This study demonstrates that NR4A2 and HuR regulate genes and signaling pathways that enhance tumorigenesis and targeting NR4A2 and HuR expression with an NR4A2 inverse agonist represents a novel regimen for treating PDAC.

Lespedeza bicolor is a shrub plant that has been widely distributed in East Asia. The methanol extract from its LBR has been shown to exhibit anticancer and anti-bacterial effects. However, its anticancer efficacy in TNBC remains uncertain. This work aimed to study the anti-TNBC effect of LBR ethanol extract and its underlying mechanism. LBR triggered the cell death in TNBC through inhibiting cell proliferation, S-phase cell arrest, and induction of apoptosis. RNA-seq analysis revealed that the genes altered by LBR treatment were predominantly enriched in the cell adhesion. Notably, LBR inhibited phosphorylation and distribution of FAK. Furthermore, LBR demonstrated significant anticancer activity in xenograft tumors in mice through inhibiting cancer cell growth and inducing apoptosis. This work demonstrated the anticancer efficiency of LBR in TNBC without causing significant adverse effect, which providing a foundation for developing LBR based chemotherapeutic agents for breast cancer therapy.

Objective: To investigate the anesthetic and analgesic effects of combining general anesthesia with an anterior quadratus lumborum block at the lateral supra-arcuate ligament (SA-AQLB) in elderly patients undergoing laparoscopic radical resection for colorectal cancer (CRC).

Methods: In this prospective study, 92 elderly patients scheduled for radical CRC resection were randomly divided into three groups: ultrasound-guided SA-AQLB group (SA group, n=31), ultrasound-guided subcostal AQLB (SC-AQLB) group (SC group, n=31), and a general anesthesia-only group (GA group, n=30). Measurements included mean arterial pressure (MAP) and heart rate (HR) at predefined time points, ranging from pre-operation to the end of surgery. Visual analog scale (VAS) pain scores were recorded at multiple postoperative time points up to 48 hours. Additional data collected included intraoperative drug dosages, anesthetic recovery times, patient-controlled intravenous analgesia (PCIA) usage, Lovett muscle strength scores, and early postoperative recovery indicators.

Results: The SA group consistently showed lower MAP and HR compared to the SC group, which in turn was lower than the GA group during the monitored time points (all P<0.05). Sensory block levels were significantly higher in the SA group than that in the SC group (P<0.05). Postoperative VAS scores were also significantly lower in the SA group compared to the other groups at all recorded times (all P<0.05). The SA group required lower doses of propofol, remifentanil, and sufentanil, but higher doses of ephedrine compared to the SC and GA groups (all P<0.05). Anesthesia recovery time was shorter in the SA group, and the total number of PCIA pump presses was least in the SA group (P<0.05). Early ambulation was achieved sooner in the SA and SC groups (P<0.05), and the incidence of nausea and vomiting was reduced in these groups compared to the GA group (P<0.05).

Conclusion: General anesthesia combined with ultrasound-guided SA-AQLB provides superior outcomes to general anesthesia alone in elderly patients undergoing laparoscopic CRC surgery. This approach significantly reduces general anesthesia drug dosage, decreases postoperative pain, minimizes perioperative adverse events, and accelerates patient recovery.

Objective: Rectal cancer has a high incidence and its onset age is getting younger. Currently, conventional laparoscopic surgery can no longer meet the clinical requirements for surgical incisions. Natural orifice specimen extraction surgery (NOSES) is less invasive, but there have been few studies on the effectiveness of this procedure for rectal cancer. Therefore, this study aimed to explore the efficacy of NOSES and conventional laparoscopic surgery in rectal cancer treatment.

Methods: In this retrospective analysis, we collected clinical data of 150 rectal cancer patients. Patients who received NOSES were included in a NOSES group and those underwent routine laparoscopic surgery were in a control group. Then, the observation group was matched with the control group at a ratio of 1:1 by using the propensity score matching method. We compared the surgical indicators, postoperative recovery indicators, physical indicators, pain, surgical stress-related indicators, inflammation indicators, immune indicators, quality of life, and postoperative complications between the two groups.

Results: We found that compared with the control group, the NOSES group had a shorter exhaust start time, getting out-of-bed activity time, length of hospital stay, bowel sound recovery time, and gastrointestinal peristalsis time. The Pittsburgh Sleep Quality Index (PSQI) and Positive and Negative Affect Schedule (PANAS) scores decreased in both groups after surgery, with the NOSES group showing a more significant reduction. The Visual Analogue Scale (VAS) scores decreased in both groups, and the NOSES group had lower VAS scores. Additionally, the NOSES group exhibited a significant interaction effect with time (intergroup effect: F = 497.800; time effect: F = 163.100; interaction effect: F = 5.307). Superoxide dismutase (SOD) levels decreased and malondialdehyde (MDA) levels increased in both groups postoperatively; however, the NOSES group had higher SOD levels and lower MDA levels. All the above comparisons were statistically significant (P < 0.05). There was no statistically significant difference in the total complication rates between the NOSES group and the control group (Z = -0.768, P = 0.442; χ² = 2.333, P = 0.127).

Conclusion: Compared to conventional laparoscopic surgery, NOSES results in less pain and injury, a more stable mood, faster recovery, and comparable safety.

Depression is a common co-morbidity among cancer cases, which has a detrimental influence on cancer treatment and prognosis. Recent advancements in the neurobiology of depression and cancer pathophysiology have revealed several shared biobehavioral mechanisms and introduced new therapeutic strategies. In this review, we summarize the biological mechanisms driving cancer-related depression, including psychosocial factors, immuno-inflammatory processes, chronic stress, dysbiosis of gut microbiota, and medically-induced factors. Interventions used for cancer-related depression may include psychosocial therapies, pharmacological therapies, immunotherapies, psychobiological medications, and dietary strategies. This review could inspire the elucidation of possible co-occurring mechanisms and complex interactions between cancer and depression, provide an opportunity to propose faster and more effective therapies for cancer-related depression, and well as new strategies for cancer in the future.

Irradiation-resistance presents a substantial challenge in the successful application of radiotherapy for non-small-cell lung cancer (NSCLC). However, the specific molecular mechanisms responsible for irradiation-resistance have yet to be completely understood. In this research, the DNA methylation and gene expression patterns resulting from irradiation treatment were produced using the DNA methylation BeadChip and RNA-Seq. An integrated analysis was carried out to identify the genes that are differentially expressed and regulated by DNA methylation. As results, the upregulation of gene expression and downregulation of DNA methylation of hexokinase 1 (HK1), a protein associated with glycolysis, were observed in irradiation-resistant NSCLC cells. Additionally, treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC) resulted in increased expression of HK1. Furthermore, it was found that overexpression of HK1 could enhance irradiation-resistance by impacting glycolysis. Collectively, our study indicate that irradiation-induced alterations in DNA methylation lead to the upregulation of HK1, which in turn promotes glycolysis and contributes to radiotherapy resistance in NSCLC. Therefore, targeting HK1 presents a potential novel strategy for addressing the issue of radiotherapy failure in NSCLC.

Gallbladder cancer (GBC) is a malignancy with a bleak prognosis, and radical surgery remains the primary treatment option. However, the high postoperative recurrence rate and the lack of individualized risk assessment tools limit the effectiveness of current treatment strategies. This study aims to identify risk factors affecting the short-term disease-free survival (DFS) of GBC patients using machine learning methods and to build a prediction model. A retrospective analysis was conducted on the clinical data from 328 GBC patients treated at the First Affiliated Hospital of Huzhou University from 2008 to 2021. Patients were randomly divided into a training set (n=230) and a validation set (n=98). Clinical data, laboratory indexes, and follow-up data were collected. Univariate Cox regression analysis identified age, tumor T-staging, lymph node metastasis, differentiation degree, and CA199 level as prognostic factors affecting DFS (all P<0.05). A prediction model constructed using the LASSO regression achieved AUCs of 0.827 and 0.801 for predicting 1-year and 3-year DFS, respectively. Notably, the XGBoost regression model showed higher prediction accuracy with AUCs of 0.922 and 0.947, respectively. The Delong test confirmed that the XGBoost model had significantly higher AUC values compared to the LASSO model (all P<0.001). In the validation set, the XGBoost model demonstrated AUCs of 0.764 and 0.761 for predicting 1-year and 3-year DFS, respectively. Overall, the XGBoost regression model demonstrates high accuracy and clinical value in predicting short-term DFS in GBC patients after radical surgery, offering a valuable tool for personalized treatment.