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Circular RNA (circRNA), a kind of special endogenous RNA, has been shown to be implicated in crucial biological processes of multiple cancers as a gene regulator. However, the functional roles of circRNAs in breast cancer (BC) remain to be poorly explored, and relatively incomplete knowledge of circRNAs handles the identification and prediction of BC-related circRNAs. Towards this end, we developed a systematic approach to identify circRNA modules in the BC context through integrating circRNA, mRNA, miRNA, and pathway data based on a non-negative matrix factorization (NMF) algorithm. Thirteen circRNA modules were uncovered by our approach, containing 4164 nodes (80 circRNAs, 2703 genes, 63 miRNAs and 1318 pathways) and 67,959 edges in total. GO (Gene Ontology) function screening identified nine circRNA functional modules with 44 circRNAs. Within them, 31 circRNAs in eight modules having direct relationships with known BC-related genes, miRNAs or disease-related pathways were selected as BC candidate circRNAs. Functional enrichment results showed that they were closely related with BC-associated pathways, such as 'KEGG (Kyoto Encyclopedia of Genes and Genomes) PATHWAYS IN CANCER', 'REACTOME IMMUNE SYSTEM' and 'KEGG MAPK SIGNALING PATHWAY', 'KEGG P53 SIGNALING PATHWAY' or 'KEGG WNT SIGNALING PATHWAY', and could sever as potential circRNA biomarkers in BC. Comparison results showed that our approach could identify more BC-related functional circRNA modules in performance. In summary, we proposed a novel systematic approach dependent on the known disease information of mRNA, miRNA and pathway to identify BC-related circRNA modules, which could help identify BC-related circRNAs and benefits treatment and prognosis for BC patients. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A computational approach was developed to identify dysregulated lncRNA-involved FFLs in breast cancer subtypes. • We investigated the common and specific FFLs in breast cancer subtypes. • We identified the survival-associated FFLs and the potential drugs for breast cancer subtypes. Abstract Previous studies have demonstrated that transcription factor-miRNA-gene feed-forward loops (FFLs) played important roles in tumorigenesis. However, the lncRNA-involved FFLs have not been explored very well. Understanding the characteristics of lncRNA-involved FFLs in breast cancer subtypes may be a key question with clinical implications. In this study, we firstly constructed an integrated background regulatory network. Then, based on mRNA, miRNA, and lncRNA differential expression, we identified 147, 140, 284, 1031 dysregulated FFLs for luminal A, luminal B, HER2+ and basal-like subtype of breast cancer, respectively. Importantly, the known breast cancer-associated lncRNAs and miRNAs were enriched in the identified dysregulated FFLs. Through merging the dysregulated FFLs, we constructed the regulatory sub-network for each subtype. We found that all sub-networks were enriched in the well-known cancer-related pathways, such as ce ll cycle , pathways in cancer. Next, we also identified potential prognostic FFLs for subtypes of breast cancer, such as the hsa-miR-182-5p_JUN_XIST in basal-like subtype. Finally, we also discussed the potential application of inferring the candidate drugs for breast cancer treatment through modulating the lncRNA expression in the dysregulated FFLs. Collectively, this study elucidated the roles of lncRNA-involved FFLs in breast cancer subtypes, which could contribute to understanding breast cancer pathogenesis and improving the treatment. [ABSTRACT FROM AUTHOR]

To investigate the effect of equivalent uniform dose (EUD)-based optimization on radiotherapy planning for left-sided breast cancer after mastectomy. Twelve patients treated with left-sided breast cancer using volumetric modulated arc therapy (VMAT) were retrospectively enrolled in this study. Four plans were generated for each patient. Plan A was optimized based on only physical parameters. EUD with α > 0 to organ at risk (OARs) was added in Plan B on the basis of Plan A; EUD with α < 0 to planning tumor volume (PTV) was added in Plan C on the basis of Plan A; EUD constraints were added for both OARs and PTV in Plan D. The quality of plans was evaluated in terms of V x (volume percent of PTV or OARs received xGy dose), D x (dose received by volume above x% of PTV or OARs), conformity index (CI), mean dose (D mean), maximum dose (D max) and minimum dose (D min). For PTV: Plan A vs. Plan B, the difference of D 2 and CI was statistically significant (P < 0.05); Plan A vs. Plan C, the differences in D 98 , D mean and HI were statistically significant (P < 0.05); Plan A vs. Plan D, differences in D 2 , D mean and HI were statistically significant (P < 0.05). For OARs: Plan A vs. Plan B, and Plan A vs. Plan D, the differences in V 5 , V 10 , V 20 , V 30 , D mean of the left lung and V 10 , V 20 , V 30 , D mean of the heart were statistically significant (P < 0.05), the differences in D mean of the thyroid and contralateral breast and the D 2 and D max of spinal cord and spinal cord planning risk volume (PRV) were statistically significant (P < 0.05); Plan A vs. Plan C, only the difference in D max of spinal cord was statistically significant (P < 0.05). Compared with DV condition, the dosimetric data with EUD-based optimization for OARs and PTV confer advantages in terms of the mean dose region of the left lung, heart, thyroid and contralateral (right) breast and the maximum dose of the spinal cord, and the improvement of the conformity and homogeneity of the target. • VMAT plans shows advantage in radiotherapy for left-sided breast cancer. • EUD-based VMAT optimization for left-sided breast cancer was studied firstly. • EUD optimization remedies the defects of DV function. • Results show conformity and homogeneity of target were promoted by using EUD. • OARs were protected based on the EUD optimization. [ABSTRACT FROM AUTHOR]