Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer.

BACKGROUND: Breast cancer (BC), a leading malignant disease, affects women all over the world. Cancer associated fibroblasts (CAFs) stimulate epithelial-mesenchymal transition, and induce chemoresistance and immunosuppression. AIM: To establish a CAFs-associated prognostic signature to improve BC patient outcome estimation. METHODS: We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas (TCGA) databases, and 3661 BC samples from the The Gene Expression Omnibus. CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm. CAF-associated gene identification was done by weighted gene co-expression network analysis. A CAF risk signature was established via univariate, least absolute shrinkage and selection operator regression, and multivariate Cox regression analyses. The receiver operating characteristic (ROC) and Kaplan-Meier curves were employed to evaluate the predictability of the model. Subsequently, a nomogram was developed with the risk score and patient clinical signature. Using Spearman's correlations analysis, the relationship between CAF risk score and gene set enrichment scores were examined. Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Employing an 8-gene (IL18, MYD88, GLIPR1, TNN, BHLHE41, DNAJB5, FKBP14, and XG) signature, we attempted to estimate BC patient prognosis. Based on our analysis, high-risk patients exhibited worse outcomes than low-risk patients. Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis. ROC analysis exhibited satisfactory nomogram predictability. The area under the curve showed 0.805 at 3 years, and 0.801 at 5 years in the TCGA cohort. We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes. CAF risk score was significantly correlated with most hallmark gene sets. Finally, the prognostic signature were further validated by qRT-PCR. CONCLUSION: We introduced a newly-discovered CAFs-associated gene signature, which can be employed to estimate BC patient outcomes conveniently and accurately.

[Effect of primary neck-shaft angle after operation on the treatment of proximal humerus fracture by locking plate].

OBJECTIVE: To explore the effect of postoperative initial neck stem angle on the treatment of proximal humeral fractures with locking plate. METHODS: From June 2014 to Septembetr 2016, 62 patients with proximal humeral fractures underwent internal fixation with locking plates were retrospectively analyzed, including 29 males and 33 females with an average age of(55.95±9.48) years old ranging from 34 to 74 years old. According to the difference of the initial neck stem angle, the patients were divided into three groups, 15 patients in the varus group had less than 127° postoperative initial neck-shaft angle, 36 patients in the normal group had 127° to 145° postoperative initial neck-shaft angle, 11 patients in the valgus group had more than 145° postoperative initial neck-shaft angle. The operating time, fracture healing time, complications, the visual analogue scale(VAS) and shoulder functional Neer scores among three groups were compared for analysis. RESULTS: All 62 patients were followed up for 17.2 months(ranged 12 to 38 months). Operative time, fracture healing time and VAS were(2.37±0.59) hours, (3.99±0.48) months and(3.67±2.02) points in the varus group;(2.60±0.49) hours, (3.78±0.49) months and(3.22±2.06) points in the normal group;(2.75±0.39) hours, (3.82±0.42) months and (4.09±1.58) points in the valgus group. There was no statistical difference in operating time, fracture healing time and VAS among these groups(P>0.05). The Neer score(87.14±6.48) in the normal group and(84.31±9.05) in the valgus group was significantly better than(75.93±9.77) in the varus group (P<0.05). Among them, 4 cases occurred complications in the varus group;2 cases in the normal group;while no complication occurred in the valgus group. CONCLUSIONS: The internal fixation with locking plates of the proximal humerus fractures with postoperative initial neck-shaft angle more than 127° can reduce complications, improve shoulder function and allow for better postoperative outcome.

Surgical exposures of the distal humeral fractures: An anatomical study of the anterior, posterior, medial and lateral approaches.

PURPOSE: Exposure of the articular surface is the key to the successful treatment of intra-articular fractures of distal humerus. Anterior, posterior olecranon osteotomy as well as medial and lateral approaches are the four main approaches to the elbow. The aim of this study was to compare the exposure of distal articular surfaces of these surgical approaches. METHODS: Twelve cadavers were used in this study. Each approach was performed on six elbows according to previously published procedures. After completion of each approach, the exposed articular surfaces were marked by inserting 0.5 mm K-wires along the margins. The elbow was then disarticulated and the exposed articular surfaces were painted. The distal humeral articular surfaces were then closely wrapped using a piece of fibre-glass screen net with meshes. The exposed articular surfaces and the total articular surfaces were calculated by counting the number of meshes, respectively. RESULTS: The average percentages of the exposed articular surfaces for the anterior, posterior olecranon osteotomy, medial and lateral approaches were 45.7% ± 2.0%, 53.9% ± 7.1%, 20.6% ± 4.9% and 28.5% ± 6.3%, respectively. CONCLUSION: The anterior and posterior approaches provide greater exposures of distal humeral articular surface than the medial and lateral ones in the treatment of distal humeral fractures.

Meta-analysis of the association between three microRNA polymorphisms and breast cancer susceptibility.

Single nucleotide polymorphisms (SNPs) in three microRNAs (miRNAs), rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499, have been associated with breast cancer (BC) susceptibility, but the evidence is conflicting. To obtain a more robust assessment of the association between these miRNA variants and BC risk, we carried out a meta-analysis through systematic literature retrieval from the PubMed and Embase databases. A total of 9 case-control studies on rs2910164, 12 on rs11614913, and 7 on rs3746444 were included. Pooled odds ratios and 95% confidence intervals were used to evaluate associations with BC risk. Overall analysis showed that rs2910164 was not associated with BC susceptibility in any genetic model, whereas rs11614913 was associated with a decreased risk in both the allelic contrast and recessive models, and rs3746444 imparted an increased risk in all genetic models. Stratified analyses showed that rs11614913 may decrease the risk of BC in the heterozygote model in Asians, and in all genetic models, except the heterozygote model, when the sample size is ≥ 500. Subgroup analysis indicated that rs3746444 was associated with increased risk of BC in Asians, but not Caucasians, at all sample sizes. This meta-analysis suggests that rs11614913 in miR-196a2 may decrease the risk of BC, while rs3746444 in miR-499 may increase it, especially in Asians when the sample size is large. We propose that rs11614913(C > T) and rs3746444 (A > G) may be useful biomarkers predictive of BC risk.

Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

OBJECTIVE: Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. METHODS: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). RESULTS: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. RESULTS indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67 (P=0.105). CONCLUSIONS: Patients with MIBC who overexpress Ki-67 and with negative hormonal receptors have relatively substantial risk of relapse within the first five years after surgery. However, adjuvant chemotherapy can only improve the outcomes of ER(-)/PR(-) patients, but not those who overexpress Ki-67. Further studies with prolonged follow-up of large cohorts are recommended to assess the prognostic significance and treatment of this lesion.