Comprehensive Analysis of the Immune-Oncology Targets and Immune Infiltrates of N 6-Methyladenosine-Related Long Noncoding RNA Regulators in Breast Cancer.

Breast cancer (BRCA) has become the highest incidence of cancer due to its heterogeneity. To predict the prognosis of BRCA patients, sensitive biomarkers deserve intensive investigation. Herein, we explored the role of N 6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) as prognostic biomarkers in BRCA patients acquired from The Cancer Genome Atlas (TCGA; n = 1,089) dataset and RNA sequencing (RNA-seq) data (n = 196). Pearson's correlation analysis, and univariate and multivariate Cox regression were performed to select m6A-related lncRNAs associated with prognosis. Twelve lncRNAs were identified to construct an m6A-related lncRNA prognostic signature (m6A-LPS) in TCGA training (n = 545) and validation (n = 544) cohorts. Based on the 12 lncRNAs, risk scores were calculated. Then, patients were classified into low- and high-risk groups according to the median value of risk scores. Distinct immune cell infiltration was observed between the two groups. Patients with low-risk score had higher immune score and upregulated expressions of four immune-oncology targets (CTLA4, PDCD1, CD274, and CD19) than patients with high-risk score. On the contrary, the high-risk group was more correlated with overall gene mutations, Wnt/ß-catenin signaling, and JAK-STAT signaling pathways. In addition, the stratification analysis verified the ability of m6A-LPS to predict prognosis. Moreover, a nomogram (based on risk score, age, gender, stage, PAM50, T, M, and N stage) was established to evaluate the overall survival (OS) of BRCA patients. Thus, m6A-LPS could serve as a sensitive biomarker in predicting the prognosis of BRCA patients and could exert positive influence in personalized immunotherapy.

The Efficacy and Toxicity of Neoadjuvant Chemotherapy Regimens of Epirubicin Plus Cyclophosphamide Followed by Docetaxel or Paclitaxel in Female Breast Cancer Patients.

PURPOSE: To retrospectively analyze the efficacy and toxicity of epirubicin plus cyclophosphamide followed by docetaxel (EC-D) and epirubicin plus cyclophosphamide followed by paclitaxel (EC-P) efficacy as neoadjuvant chemotherapy regiments by pathological complete response (pCR) in this study. METHODS: In total, 455 patients diagnosed with breast cancer who received NAC from January 2014 to January 2019 were enrolled. Of which, 109 patients received EC-D (E: 90, C: 600, D: 80, all in mg/m2) and 346 were treated with EC-P (E: 90, C: 600, D: 175, all in mg/m2). Efficacy of NAC regimens was evaluated by pCR, and the toxicity was studied. Chi-squared test was used at p=0.05. RESULTS: In EC-D, 11 patients received ypT0/isN0, and 6 of them got ypT0N0. Analogously, 67 patients receiving received EC-P obtained ypT0/isN0, and 43 people of them acquired ypT0N0. The rate of pCR in EC-P was higher than EC-D. Patients with ER (-), PR (-), Her-2 (+) and high Ki-67 index were easier to were more likely to acquire pCR. Two pCRs were described, the pCR of NAC differed according to the definition. In terms of side effects, there was no significant difference in platelet and urea, but the decrease of hemoglobin and creatinine levels after EC-P treatment was more significant than that after EC-D treatment. CONCLUSION: The efficacy of EC-P is better than EC-D if pCR is to be determined as a surrogate end-point for prognosis. The patients with anemia or renal insufficiency who need to receive NAC should choose EC-D.

Effects of Chemotherapy on Serum Lipids in Chinese Postoperative Breast Cancer Patients.

PURPOSE: Chemotherapy is a comprehensive therapy for breast cancer; nevertheless, its associated adverse effects are drawing increasing attention with the continuous improvement of the efficacy. The changes in serum lipids of breast cancer patients caused by chemotherapy have been reported by previous studies, whereby the former increase the incidence rate of cardiovascular disorders. However, the variations in the changes of serum lipids with different chemotherapy regimens have seldom been reported. METHODS: From January 2011 to December 2017, 1740 breast cancer patients treated with chemotherapy were recruited at the First Affiliated Hospital of Nanjing Medical University. The chemotherapy regimens included anthracycline-based, taxane-based, and anthracycline-plus-taxane-based regimens, dose-dense and standard-interval regimens. Lipid profiles that contained TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol) and Lpa (lipoprotein a) levels were collected prior to the first, second and last cycles of chemotherapy. The changes of serum lipids with the same or different chemotherapy regimens were analyzed and compared. RESULTS: It was observed that the levels of TG, TC, LDL-C and Lpa increased significantly while that of HDL-C decreased after adjuvant chemotherapy in breast cancer patients (P<0.05). Besides, dose-dense regimens had more influence in TG and HDL-C and less influence in TC and LDL-C than standard-interval regimens. HDL-C was more sensitive to anthracycline-based regimens than taxane-based regimens. The level of TG with anthracycline-plus-taxane-based regimens was higher than that with only anthracycline-based or taxane-based regimens, and the level of HDL-C with anthracycline-plus-taxane-based regimen showed lower than that with taxane-based regimen. CONCLUSION: In summary, this study proposed that dyslipidemia was strongly associated with chemotherapy in Chinese breast cancer patients after operative treatment. Furthermore, the changes in levels of serum lipids varied among patients with different chemotherapy regimens and taxane had less effect on dyslipidemia than anthracycline.

Involvement of a novel circularRNA, hsa_circ_0000520, attenuates tumorigenesis of cervical cancer cell through competitively binding with miR-146b-3p.

The implication of circular RNAs (circRNAs) in the pathogenesis of human cervical cancer (CC) has been demonstrated by numerous of researches, nevertheless, the whole regulatory network of circRNAs in CC remains unclear. In the present study, two GSE data sets (GSE113696 and GSE102686) were enrolled to analysed different expressed circRNA. We found that hsa_circ_0000520(circ_0000520) was decreased in CC tissues and cell lines. Functional studies indicated circ_0000520 overexpression in vitro repressed CC cell proliferation, invasion and migration, while promoted CC cell apoptosis. Moreover, circ_0000520 overexpression in vivo repressed CC tumour growth. Mechanismly, circ_0000520 and PAX5 were revealed to directly bind to miR-146b-3p, and circ_0000520 could indirectly regulate PAX5 by sponging miR-146b-3p. In conclusion, circ_0000520 repressed CC progression in vitro and in vivo by sponging miR-146b-3p to release PAX5.