Background Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment. Methods 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm. Results We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P = 0.00018 and P = 0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion. Conclusions We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.
Background: Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and strong heterogeneity. TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment.Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas (TCGA) database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort (N = 59). Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The signature related mRNAs were identified using the Pearson correlation. Functional enrichment analysis of related mRNA was performed using the Metascape. The qPCR assay was performed to confirm the expressions and clinicopathological correlationsof two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm.Results:We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. In both the training and validation cohort, patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores(P=0.00018 and P =0.0068 respectively). 1, 5, 8-year AUC in the training cohort were 1.000, 1.000 and 0.908 respectively, in the validation cohort were 0.785, 0.790 and 0.892 respectively indicating that our signature has a good prognostic capacity. Signature related mRNA mainly enriched in terms include RNA metabolic process, DNA repair pathways, and so on. Two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed in TNBC without gBRCAm, and significantly associated with tumor grade and invasion.Conclusions: We constructed a novel 8-lncRNA signaturewhich significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targetswhich function needed further exploration.
Background: It is very important to understand and explore its carcinogenic effect for the study of effective therapeutic methods. Current studies have shown that ITGA2 plays an important role in some tumors, but it has not been reported in other human cancers, and no systematic pan-cancer analysis has been carried out. Method: In this study, we used the online databases,for example GEPIA, THE HUMAN PROTEIN Atlas (THPA) , UALCAN, CPTAC and TIMER, to analyze ITGA2 in HUMAN tumors by analyzing TCGA and GEO medium datasets. Results: Through the analysis of online database, we found that ITGA2 was differentially expressed in many kinds of tumors. There was a significant correlation between the differential expression of OS and DFS in hepatocellular carcinoma and Kidney renal clear cell carcinoma. At the same time, we also compared the degree of methylation between normal tissues and tumor tissues, and found that there were obvious methylation differences, such as liver cancer, cholangiocarcinoma, lung cancer and so on. We also evaluated the association between ITGA2 mutation and prognosis and found no significant association between ITGA2 mutation with OS. In addition, by predicting differences in the expression of ITGA2 in immunotherapy, we found that there were significant differences in the expression of ITGA2 in urothelial carcinoma, and explored the role and significance of ITGA2 in immune infiltration and biological process. Conclusion: ITGA2 has been shown to play an important role in carcinogenesis in human tumors by pan-cancer analysis.
Approximately 80 million Americans have limited health literacy, and lower health literacy has been associated with both poorer access to care and health outcomes. 3 The American Medical Association and the National Health Institutes recommend that the readability of patient education materials be at reading grade level 6 or lower. 4 The average patient reads at grade level 7, and nearly 20% of Americans have difficulty comprehending reading grade level 4 text. [3][4][5] This indicates that currently available online resources for PV and BP are on average at least six reading grades higher than recommended and at least five grades higher than the average patient's reading ability. Remarkably, we found that resources written by medical doctors, and especially by dermatologists, had higher ARGL than those written by non-medical doctors.Limitations of our study included the cross-sectional design and possible multi-rater variability across the different validated readability measures. Additionally, using "pemphigus" and "pemphigoid" as search terms may have increased the grade level of resources. Our findings highlight the need to develop online patient education resources that are accessible to a higher proportion of patients and to actively involve content providers and patients in resource development.
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