RESUMO
BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.
RESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination. METHODS: In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases. RESULTS: In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01-1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data. CONCLUSIONS: This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.
Assuntos
Neoplasias Colorretais , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudo de Associação Genômica Ampla , Multiômica , Inquéritos Nutricionais , Ácidos Graxos , Doença Pulmonar Obstrutiva Crônica/genética , Neoplasias Colorretais/genéticaRESUMO
BACKGROUND: Colorectal cancer (CRC) is a disease with high morbidity and mortality rates globally. Long noncoding RNAs (lncRNAs) play a fundamental role in tumor progression, and increasing attention has been paid to their role in CRC. This study aimed to determine the function of lncRNA DICER1 antisense RNA 1 (DICER1-AS1) in CRC and confirm its potential regulatory mechanisms in CRC. METHODS: The publicly available dataset was used to assess DICER1-AS1 function and expression in CRC. RT-qPCR or western blot assays were performed to verify DICER1-AS1, miR-650, and mitogen-activated protein kinase 1 (MAPK1) expression in CRC cells or tissues. To determine the function of DICER1-AS1, we performed CCK-8, colony formation, transwell, cell cycle, and in vivo animal assays. Using RNA sequence analysis, luciferase reporter assays, and bioinformatics analysis, the connection between DICER1-AS1, MAPK1, and miR-650 was investigated. RESULTS: DICER1-AS1 was significantly upregulated in CRC tissue compared to normal colon tissue. High DICER1-AS1 expression suggested a poor prognosis in CRC patients. Functionally, upregulation of DICER1-AS1 effectively promoted CRC proliferation, migration, and invasion ex vivo and tumor progression in vivo. Mechanistically, DICER1-AS1 functions as a competitive endogenous RNA (ceRNA) that sponges miR-650 to upregulate MAPK1, promotes ERK1/2 phosphorylation, and sequentially activates the MAPK/ERK signaling pathway. CONCLUSION: Our investigations found that upregulation of DICER1-AS1 activates the MAPK/ERK signaling pathway by sponging miR-650 to promote CRC progression, revealing a possible clinically significant biomarker and therapeutic target.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Gastric cancer (GC) is a globally important disease. It is the 5th most common malignancy and the 4th most common cause of death from cancer in the world. Patients with GC are often at an advanced stage when they are first diagnosed, and their overall prognosis is poor due to locally advanced and distant metastasis. This study sought to establish a predictive model of GC distant metastasis and survival that can be used to guide individualized treatment. METHODS: Patients diagnosed with GC from the Surveillance, Epidemiology, and End Results database were enrolled in the study. Univariate and multivariate logistic regression analyses were used to identify risk and prognostic factors for GC patients with distant metastasis. The factors were then used to construct nomograms to predict the probability of distant metastasis and the survival time of GC patients. Receiver operating characteristic (ROC) curve and decision curve analyses were used to verify the prediction ability of the nomograms. RESULTS: We established a comprehensive nomogram to predict the survival time of GC patients and 4 nomograms to predict distant metastasis. Nomograms could help oncologists to formulate treatment strategies and provide hospice care under an overall management model. CONCLUSIONS: Establishing a prediction model for distant metastasis and the survival of GC patients is of great clinical significance. The prediction of distant metastasis could help clinicians to make individualized assessments of patients and formulate individualized examination measures. Survival prediction models could help oncologists to formulate good treatment strategies and provide hospice care.
RESUMO
BACKGROUND: It is now recognized that the symptoms of colon cancer differ according to whether the tumor is located on the left or right side of the patient. The results of the present study point to the differences in the tissue and embryonic origins of left- and right-sided colon cancer that cause the variations in molecular typing. The research purpose of this study is to establish a core differential gene scoring model and proved its effect. METHODS: We downloaded transcriptome data and clinical information from The Cancer Genome Atlas (TCGA). A total of 243 patients in stages II and III were grouped according to the colon cancer site. Then we screened for differential transcriptome products. The corresponding differential gene were performing a corresponding protein interaction analysis. We used 12 algorithms in Cytoscape to calculate the hub genes and a total of 37 hub genes were obtained finally. We extracted the first principal component value (PC1) of the hub genes to evaluate the effectiveness of screening. Cox regression analysis was performed for the differential genes. Finally, we performed a prognostic analysis on right-sided colon cancer patients using the BST2 gene, PC1 and relevant clinical information. RESULTS: After screening for differentially expressed genes, 37 hub genes were obtained with appropriate algorithms. PC1 showed differences in hub genes between left- and right-sided colon cancer patients. BST2 and 31 other genes were identified as significant by Cox regression analysis and were significantly mutated in patients with right-sided colon cancer. Finally, we selected the BST2 gene and relevant clinical information as the prognostic factors to build a scoring model. The prediction effect of the model was satisfied. CONCLUSIONS: We constructed a prognostic model based on BST2, PC1, and other relevant clinical information and proved its good effect.