Objective: Increasing evidence highlights the roles of N6-methyladenosine (m6A) and its regulators in oncogenesis. Herein, this study observed the associations of m6A regulators with breast cancer.Methods: RNA-seq profiles of breast cancer were retrieved from the Cancer Genome Atlas (TCGA) database. The expression of m6A regulators was analyzed in tumor and normal tissues. Their expression correlations were analyzed by Spearson test. Overall survival (OS) analysis of these regulators was then presented. Gene set enrichment analysis (GSEA) was performed in high and low YTHDF1 expression groups. The correlations of YTHDF1 expression with immune cells and tumor mutation burden (TMB) were calculated in breast cancer samples. Somatic variation was assessed in high and low YTHDF1 expression groups.Results: Most of m6A regulators were abnormally expressed in breast cancer compared to normal tissues. At the mRNA levels, there were closely relationships between them. Among them, YTHDF1 up-regulation was significantly related to undesirable prognosis (p = 0.025). GSEA results showed that high YTHDF1 expression was associated with cancer-related pathways. Furthermore, YTHDF1 expression was significantly correlated with T cells CD4 memory activated, NK cells activated, monocytes, and macrophages. There were higher TMB scores in YTHDF1 up-regulation group than its down-regulation group. Missense mutation and non-sense mutation were the most frequent mutation types.Conclusion: Our findings suggested that dysregulated m6A regulator YTHDF1 was predictive of survival outcomes as well as response to immunotherapy of breast cancer, and were closely related to immune microenvironment.
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Background:The prognostic role of axillary lymph node ratio (LNR) after neoadjuvant chemotherapy (NAC) in breast cancer has not been illuminated. This study was designed to investigate the prognostic role of LNR in breast cancer compared with traditional ypN stage.
Material/Methods:A total of 306 breast cancer patients diagnosed with positive axillary lymph nodes from January 2007 to December 2014 were eligible for this retrospective analysis. All enrolled patients were treated with a median of 4 cycles of NAC followed by mastectomy and level I, II, and III axillary lymph node dissection (ALND).
Results:The median duration of follow-up was 78 months (range, 7-147 months). Univariate analysis indicated that both the LNR category (P<0.001) and ypN stage (P<0.001) were significant associated with event-free survival (EFS) and overall survival (OS). However, multivariate analysis indicated that the LNR category was independently associated with EFS (P<0.001) and OS (P<0.001), while the ypN stage showed no statistical effect on EFS (P=0.391) or OS (P=0.081). On additional analyses stratified by molecular subtypes, we found that the prognosis of triple negative breast cancer could be better discriminated when the cutoff value of LNR was set at 0.15.
Conclusions:LNR showed a superior predictive value in evaluating prognosis of breast cancer patients after NAC. In addition, the LNR cutoff point 0.15 can accurately discriminate survival outcomes for different triple negative breast cancer subtypes.
Background: Although stage IIIC (any TN3M0) breast cancer is known to have a dismal prognosis, the clinical outcome of current standard management and the prognostic differences between N3a, N3b and N3c remain to be further investigated. Material and Methods: Data from our center on pathologic N3 (pN3) (n=284) breast cancer and the US Surveillance, Epidemiology, and End Results (SEER) database on clinical N3 (cN3) (n=15,291) and M1 (n=23,623) breast cancer between January 2004 and December 2015 were systematically analyzed for clinicopathological characteristics and survival outcomes. Results: In our institution, patients with pN3c had the worst survival, with 5-year OS and DFS rates of 52.4% and 41.5%, respectively. Patients with pN3b had a relatively good prognosis, with a 5-year OS rate of 75.3% vs 63.9% for the pN3a group (p=0.045). For DFS, the 5-year survival rate was 63.1% in the pN3b group compared with 40.3% in the pN3a group (p=0.030). In the US SEER database, patients with cN3c had the worst survival in the cN3 group, but the prognosis of cN3c was much better than that of M1. Similarly, patients with cN3b had a better prognosis compared with patients in other groups, with a 5-year OS rate of 68.9% vs 61.9% for the cN3a group (p<0.001) and a 5-year BCSS rate of 73.4% vs 67.1% for the cN3a group (p<0.001). Conclusion: Breast cancer patients with N3c had the worst clinical outcomes, while the prognosis of N3b patients was better than that of N3a patients.
To investigate the relationship between the expression of RASSF1A protein and promoter hypermethylation of RASSF1A gene, RASSF1A protein expression was measured by Western blotting in 10 specimens of normal bladder tissues and 23 specimens of bladder transitional cell carcinoma (BTCC). The promoter methylation in BTCC and normal bladder tissues was detected by methylation-specific PCR (MSP). The results showed that the expression level of RASSF1A protein was significantly lower in BTCC tissues than that in normal bladder tissues. However, it was not correlated with its clinical stages and pathological grades. The frequency of promoter methylation of RASSF1A gene was higher in BTCC tissues than that in normal bladder tissues. In 14 patients with the aberrant promoter methylation, 13 showed loss or low expression of RASSF1A protein. It is concluded that RASSF1A gene promoter methylation may contribute to the low level or loss of RASSF1A protein expression, the inactivation of RASSF1A gene and the genesis of BTCC. But, it may bear no correlation with its clinical stages and pathological grades.
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