Discover. Oncology最新文献

This study aimed to identify the candidate genes of dihydroartemisinin (DHA) in acting against hepatocellular carcinoma (HCC), as well as its association with lipid metabolism-related genes (LMRGs), thereby providing a basis for the application of DHA in anti-HCC therapy.

Methods: Potential candidate genes of DHA were predicted using databases. Differentially expressed genes (DEGs) were screened from HCC datasets in the Gene Expression Omnibus (GEO) database. Common candidate genes of DHA and HCC were obtained through Weighted Gene Co-expression Network Analysis (WGCNA) and intersection analysis. Protein-protein interaction (PPI) networks and Gene Ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to decipher functional pathways. Candidate genes were screened using ensemble models, followed by validation via SHapley Additive exPlanations (SHAP) analysis. Integrating data from LMRG databases, along with gene expression and survival analyses, the key genes were finally identified.

Results: A total of 306 candidate genes of DHA and 45 common candidate genes of DHA and HCC were obtained. These common candidate genes were enriched in pathways such as the p53 signaling pathway and cell cycle. 10 candidate genes, including cytochrome P450 1A2 (CYP1A2), cytochrome P450 2C19 (CYP2C19), sex hormone-binding globulin (SHBG), insulin-like growth factor 1 (IGF1), sulfotransferase family 1E member 1 (SULT1E1), cyclin-dependent kinase 1 (CDK1), aurora kinase A (AURKA), aldo-keto reductase family 1 member C3 (AKR1C3), cyclin A2 (CCNA2), and heat shock protein 90 alpha family class B member 1 (HSP90AB1) were screened out, with the model achieving an area under the receiver operating characteristic curve (AUC) of 0.961. Among these candidate genes, CYP1A2 and CYP2C19 contributed the most to the model. Three key LMRGs (CYP1A2, CYP2C19, and AKR1C3) were identified, which exhibited abnormal expression in HCC tissues and were associated with the survival of HCC patients.

Conclusion: Based on analyses of public databases and computational predictions, DHA may exert anti-HCC effects by regulating the p53 signaling pathway, cell cycle progression, and the LMRGs. However, these potential regulatory mechanisms require further experimental validation to confirm their biological relevance.

Objective: This study aimed to evaluate the value of heat shock protein 90α (HSP90α) in predicting treatment response and progression-free survival (PFS) among patients with lung cancer.

Methods: We retrospectively analyzed 585 patients with lung cancer treated at Jilin Cancer Hospital between January 2014 and December 2023. Patients were categorized by pretreatment HSP90α levels into high- and low-level groups and by posttreatment changes after four cycles into increasing and decreasing groups. We assessed the association between baseline HSP90α levels and clinical characteristics, its correlation with treatment efficacy and PFS, and its combined predictive ability with classical tumor biomarkers (CEA, NSE, and SCC).

Results: High pretreatment HSP90α levels were associated with older age and specific pathological types and served as an independent risk factor for shorter PFS. Patients with low baseline HSP90α levels exhibited a better short-term treatment response and longer PFS than did those with high baseline HSP90α levels. Increasing HSP90α after treatment correlated with an improved response and prolonged PFS. HSP90α levels were positively correlated with CEA, NSE, and SCC levels. Notably, the combination of HSP90α and CEA expression significantly enhanced PFS prediction in patients with lung adenocarcinoma.

Conclusions: HSP90α is a significant predictive biomarker for treatment efficacy and prognosis in lung cancer patients, particularly when it is combined with traditional markers such as CEA.

Objective: To assess whether a bidirectional causal relationship exists between gallbladder disease and colorectal cancer (CRC) using a two-sample, bidirectional Mendelian randomization (MR) approach based on genome-wide association study (GWAS) summary statistics.

Methods: We used European-ancestry data from the IEU OpenGWAS project within the UK Biobank. In the forward MR analysis, gallbladder disease was treated as the exposure and CRC as the outcome; in the reverse analysis, genetic liability to CRC was treated as the exposure and gallbladder disease as the outcome. The inverse variance weighted (IVW) method served as the primary analysis, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Instrument strength was evaluated using F statistics (F > 10 as the threshold for strong instruments). Sensitivity analyses included MR-Egger intercept tests for horizontal pleiotropy, Cochran's Q tests for heterogeneity, leave-one-out analyses, and visual inspection of funnel plots.

Results: In the forward analysis, 19 independent SNPs significantly associated with gallbladder disease were included, all with F statistics > 10. IVW analysis showed no significant causal association between gallbladder disease and CRC risk (odds ratio 95% confidence interval including 1, P > 0.05), and the results from MR-Egger, weighted median, and mode-based methods were directionally consistent. Some heterogeneity was observed, but there was no evidence of substantial horizontal pleiotropy, and leave-one-out and funnel plot analyses supported the robustness of the findings. In the reverse analysis, 30 SNPs associated with CRC were retained, again all with F statistics > 10. IVW and complementary MR methods consistently indicated no significant causal effect of genetic liability to CRC on the risk of gallbladder disease (P > 0.05), with no notable heterogeneity or pleiotropy detected and broadly stable sensitivity analysis results.

Conclusion: This two-sample, bidirectional MR study found no evidence for a causal relationship in either direction between gallbladder disease and CRC, suggesting that gallbladder disease and its genetic susceptibility are unlikely to be major genetic drivers of colorectal carcinogenesis. Individuals should not be classified as high-risk for CRC solely on the basis of gallbladder disease or cholecystectomy history, although coexisting metabolic risk factors still warrant comprehensive management and further study.

Background: Elderly patients with early stage T pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis for distant metastasis (DM). In this study, we aimed to construct and validate a novel nomogram for predicting distant metastasis and prognosis in elderly patients with T1-T2 PDAC.

Methods: In this study, patients diagnosed with pancreatic ductal adenocarcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2017. Univariate and multivariate logistic regression analyses were used to determine independent risk factors for distant metastasis in elderly patients with T1-T2 PDAC. Univariate and stepwise multivariate Cox regression analyses were used to determine independent prognostic factors in elderly patients with T1-T2 PDAC. two novel nomograms were developed, and the results were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results: Multivariate logistic regression analysis demonstrated that the independent risk factors for DM in elderly patients with T1-T2 PDAC included primary site, grade, N stage, T stage and sex. Stepwise multivariate Cox regression analysis indicated that age, grade, primary site, tumour size, liver metastasis, surgery and chemotherapy were independent prognostic factors. The performance of the two prediction models was further validated by the analysis of the ROC curves of the training and validation sets, calibration, DCA and Kaplan-Meier (K-M) survival curves, which confirmed their capacity to accurately predict the risk and prognosis of DM in elderly patients with T1-T2 PDAC.

Conclusion: The two nomograms are expected to serve as effective tools for predicting the risk of DM in elderly patients with T1-T2 PDAC and for providing personalized prognosis prediction in elderly T1-T2 PDAC patients with DM, which may significantly improve clinical decision-making and patient management.

Background: Growing evidence suggests that there is a link between the oral microbiota and the development of digestive system cancers (DSCs). Nonetheless, the causal relationship between the oral microbiota and DSCs has yet to be established.

Methods: To evaluate the causal relationship between oral microbiota and DSCs, we employed Genome-wide association study (GWAS) summary statistics for both oral microbiota and DSCs, in conjunction with bidirectional two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms, which were free from confounding factors, were used as instrumental variables to infer causation. Sensitivity analyses were conducted to assess the robustness of our findings. This study employed datasets encompassing a wide range of cancer cases and controls, with an emphasis on Asian populations.

Results: Our analysis of 116 oral microbiota (65 from tongue dorsum and 51 from saliva) uncovered intricate causal associations with seven types of DSCs. We discovered that the genus TM7x (OR > 1, adjusted p < 0.05) poses a risk for hepatic bile duct cancer, and the genus Leptotrichia (OR = 6.38, 95%CI = 1.84-22.10, adjusted p < 0.05) poses a risk for pancreatic cancer. Furthermore, reverse MR analysis showed that DSCs influence the relative abundance of certain oral microbiota strains.

Conclusion: Our MR analysis has confirmed that there is a causal association between the oral microbiota and DSCs. This finding offers potential for creating novel microbial markers and treatments that modify the microbiota specifically for DSC patients.

To enhance breast cancer (BC) management, there is an urgent need for molecular prognostic markers and therapeutic targets. This study investigates the role of chondroadherin (CHAD) in BC prognosis and its potential as a therapeutic target, focusing on its correlation with cancer severity and patient survival. CHAD expression at both mRNA and protein levels was analyzed in multiple datasets, and survival analysis was conducted. Comparisons were made between groups with different metastasis tendencies, and associations with clinical and pathological stages were examined. CHAD knockdown in T47D and ZR75-30 cell lines was performed to assess effects on proliferation and migration. Overexpression of CHAD in the MDA-MB-231 cell line reduced cell proliferation capability. GO/KEGG enrichment analysis identified CHAD's roles in molecular functions, cellular components, and biological processes. Western blotting evaluated CHAD's impact on the PI3K/Akt signaling pathway. Results indicated that CHAD expression is significantly lower in high malignancy BC groups and is associated with poorer survival outcomes. Increased CHAD levels correlate with lower metastasis propensity and are typically seen in lower-grade BC patients. CHAD knockdown increased proliferation and migration in T47D and ZR75-30 cells. Enrichment analyses highlighted pathways like "focal adhesion," "ECM receptor interaction," "regulation of actin cytoskeleton," and "PI3K/Akt pathway." Western blotting confirmed that CHAD inhibits PI3K and Akt phosphorylation. In summary, CHAD serves as a tumor suppressor gene and potential prognostic biomarker in breast cancer by inhibiting cell migration and proliferation through cell adhesion and PI3K/Akt pathway inhibition. Reduced CHAD expression correlates with worse prognosis, suggesting its potential as a therapeutic target.