Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.
Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.
Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.
Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献
Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.
Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.
Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury. 相似文献
ObjectivesLaryngeal cancer is a common malignant tumor that originates from the larynx, yet its molecular mechanisms have not been thoroughly explored. The purpose of this study was to identify and evaluate immune-related genes in laryngeal cancer through gene co-expression networks, which may serve as biomarkers for its immunotherapy.MethodsWe applied ESTIMATE to evaluate the immune-infiltration landscape of tumor microenvironment. The co-expression networks were constructed by weighted gene co expression network analysis (WGCNA) and compared with the existing human immune related genes (IRGs) to determine the co-expressed IRGs. GSVA combined with CIBERSORT and ssGSEA illustrated the correlation of hub genes and immune infiltration patterns. TIDE algorithm and Subclass mapping evaluated the function of hub genes in predicting immune function and immunotherapeutic sensitivity. The pRRophetic was employed in the sensitivity prediction of chemotherapeutic drugs.ResultsA total of 23 co-expressed IRGs were identified and showed robust expression characteristics. These genes were significantly related to immune infiltration patterns, immune function and sensitivity prediction of immunotherapy and chemotherapeutic drugs for laryngeal cancer patients. Genetic alteration in somatic mutation level and related pathways were also revealed.ConclusionThe 23 co-expressed IRGs may act as immunotherapeutic biomarkers and potential therapeutic targets for laryngeal cancer with certain expression robustness. The molecular mechanisms deserve further investigation, which will guide clinical treatment in the future. 相似文献
AbstractThe leading cause of death of adolescents in developed countries is injury. Alcohol is a major contributor to adolescent injury. Most of the injury deaths in youth are caused by traffic crashes. Driving under the influence (DUI) and riding with a driver who is under the influence (RUI) of alcohol increase the risk of road crash. The focus of this study is how adolescents’ risk of DUI and RUI differ in relation to their experience of parental control and peer pressure to substance use, other risky behaviours and leisure time activities. The analyses are based on data from the European School Survey Project on Alcohol and Other Drugs collected from 15- to 16-year-old Finnish adolescents in 2015 (n?=?4049, response rate 88.7%). The study shows that problems tend to entangle in some adolescent groups in which DUI and RUI are also more common. Adolescents with higher probability of using various substances, of starting alcohol use at young age, of experiencing weak parental control, and high peer pressure are at higher risk of DUI and RUI. The results indicate that professionals and authorities handling underage DUI and RUI ought to consider adolescents’ situation as a whole. 相似文献