Identification and validation of a five-gene prognostic signature based on bioinformatics analyses in breast cancer.

Background: This study aimed to identify prognostic signatures to predict the prognosis of breast cancer (BRCA) patients based on a series of comprehensive analyses of gene expression data. Methods: The RNA-sequencing expression data and corresponding BRCA patient clinical data were collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Firstly, the differently expressed genes (DEGs) related to prognosis between tumor tissues and normal tissues were ascertained by performing R package "limma". Secondly, the DEGs were used to construct a polygenic risk scoring model by the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator Cox regression (Lasso-cox) analysis method. Thirdly, survival analysis was performed to investigate the risk score values in the TCGA cohort. And the enrichment analysis, immune cell infiltration levels analysis, and protein-protein internet (PPI) analysis were performed. Simultaneously, the GEO cohort was used to validate the model. Lastly, we constructed a nomogram to explore the influence of polygenic risk score and other clinical factors on the survival probability of patients with BRCA. Results: A total of 1000 DEGs including 396 upregulated genes and 604 downregulated genes were identified from the TCGA-BRCA dataset. We obtained 5 prognosis-related genes, as the key biomarkers by Lasso-cox analysis (FBXL19, HAGHL, PHKG2, PKMYT1, and TXNDC17), all of which were significantly upregulated in breast tumors. The prognostic prediction of the 5 genes model was great in training and validation cohorts. Moreover, the high-risk group had a poorer prognosis. The Cox regression analysis showed that the comprehensive risk score for 5 genes was an independent prognosis factor. Conclusion: The 5 genes risk model constructed in this study had an independent predictive ability to distinguish patients with a high risk of death from those with a low-risk score, and it can be used as a practical and reliable prognostic tool for BRCA.

Prognostic Value of Hepatitis B Virus Infection in Very Young Patients With Curatively Resected Breast Cancer: Analyses From an Endemic Area in China.

Background: Hepatitis B virus (HBV) infection has been associated with the risk and prognosis of many malignancies. Nevertheless, the association between HBV and the prognosis of breast cancer is unclear. The objectives of this study were to investigate the prognostic role of hepatitis B surface antigen (HBsAg) and to integrate HBsAg to establish nomograms for better prognostic prediction of very young patients with breast cancer. Methods: This analysis was performed retrospectively in a cohort of 1,012 consecutive very young (≤35 at diagnosis) patients who received curative resection for breast cancer. The significance of HBsAg in the prognosis of these patients was investigated. Univariate and multivariate analyses were used to identify independent variables for disease-free survival (DFS) and overall survival (OS). Nomograms were built based on those identified variables. Results: Overall, 140 of the 1,012 patients (13.8%) were seropositive for HBsAg. The median follow-up was 67.9 (95% CI, 64.4-71.4) months for the entire population. The HBsAg-positive cohort had significantly inferior DFS (HR, 1.66; 95% CI, 1.07-2.56; P = 0.021) and OS (HR, 1.75; 95% CI, 1.10-2.79; P = 0.016) as compared with the HBsAg-negative cohort. The rates of 10-year DFS and OS were 77.4 and 73.0% in the HBsAg-positive group and 84.1 and 85.6% in the HBsAg-negative group, respectively. In multivariable analysis, HBsAg status was identified as an independent significant unfavorable prognostic factor for DFS (P = 0.01) and OS (P = 0.04) in very young patients with breast cancer. Nomograms were established and displayed good calibration and acceptable discrimination. The C-index values for DFS and OS were 0.656 (95% CI: 0.620-0.691) and 0.738 (95% CI: 0.697-0.779), respectively. Based on the total prognostic scores (TPS) of the nomograms, 3 different prognosis groups were identified for DFS and OS. Conclusions: HBsAg is an independent unfavorable prognostic factor for DFS and OS in very young patients with curatively resected breast cancer, and nomograms integrating HBsAg provide individual survival prediction to benefit prognosis evaluation and individualized therapy.

Choroidal thickness in school children: The Gobi Desert Children Eye Study.

PURPOSE: To investigate choroidal thickness (CT) and its associations in children in a school-based study. METHODS: The cross-sectional school-based Gobi Desert Children Eye Study included 1565 out of 1911 (81.9%) eligible children from all schools in the oasis region of Ejina in the Gobi Desert. A detailed ophthalmic examination was performed, including spectral-domain optical coherence tomography with enhanced depth imaging for CT measurement. RESULTS: CT measurements were available for 1463 (93.5%) students (mean age: 11.8±3.5 years; range:7-21 years). Mean subfoveal choroidal thickness (SFCT) was 282±49µm. CT was thickest at 1000µm temporal to the fovea (286±49µm), followed by the subfoveal region (282±49 µm; P<0.001), the region at 2500µm temporal to the fovea (278±49µm), the region at 1000µm nasal to the fovea (254±49µm;P<0.001), and the region at 2500µm nasal to the fovea (197±50µm;P<0.001). In cross-sectional analysis, the mean SFCT increased with age from 288µm at 7 years of age to 304µm at 11 years, and then decreased to 258 µm at 18 years. In multivariate analysis, thicker SFCT was associated (regression coefficient r:0.38) with higher hyperopic refractive error (P<0.001;standardized regression coefficient beta:0.31;non-standardized regression coefficient B:7.61;95% confidence intervals (CI):6.29,8.93), younger age (P<0.001;beta:-0.10;B:-1.39;95%CI:-2.14,-0.64), male gender (P = 0.03;beta:-0.05;B:-5.33;95%CI:-10.1,-0.53), higher corneal refractive power (P<0.001;beta:0.12;B:3.68;95%CI:2.12,5.24), and non-Han Chinese ethnicity (P = 0.03;beta:0.05;B:6.16;95%CI:0.50,11.8). Ratio of CT(1000µm nasal to fovea)/SFCT (0.90±0.06;range:0.66,1.23) and ratio of CT(2500µm nasal to fovea)/SFCT (0.70±0.13;range:0.28,1.23) decreased with older age (P = 0.01;and P = 0.001, respectively), while ratio of CT(1000µm temporal to fovea)/SFCT (1.02±0.06;range:0.56,1.37) and ratio of CT(2500µm temporal to fovea)/SFCT (0.99±0.11;range:0.54,1.84) increased with older age (both P<0.001). Time spent outdoors or indoors was not significantly associated with CT-related parameter in multivariate analysis. CONCLUSIONS: In contrast to SFCT in adults and despite elongating axial length, SFCT in children increased in cross-sectional analysis with older age (up to 11 years of age) and then started to decrease with further ageing. It suggests an increase in choroidal volume up to the age of 11 years. In children, the choroid was thickest at 1000µm temporal to the fovea, followed by the subfoveal region, and this difference significantly increased with older age. In contrast, CT nasal to the fovea in relationship to SFCT decreased with older age. CT was independent of lifestyle-associated parameters.

Prevalence of myopia in schoolchildren in Ejina: the Gobi Desert Children Eye Study.

PURPOSE: To determine the prevalence and associations of myopia in schoolchildren in provincial Western China. METHODS: In the school-based observational cross-sectional Gobi Desert Children Eye Study, cylcoplegic refractometry as part of a comprehensive ophthalmic examination was performed in all schools in the oasis region of Ejina. Out of 1911 eligible children, 1565 (81.9%) children with a mean age of 11.9 ± 3.5 years (range, 6-21 years) participated. RESULTS: The mean refractive error in the worse eye was -1.38 ± 2.04 diopters (D) (median, -0.88 D; range, -13.00 to +6.50 D). In multivariate analysis, more myopic refractive errors were associated with older age (P < 0.001; regression coefficient B: -0.26; 95% confidence interval [CI]: -0.28, -0.23), female sex (P = 0.005; B: -0.26; 95%CI: -0.43, -0.08), more myopic paternal refractive errors (P < 0.001; B: 0.20; 95%CI: 0.14, 0.27), more myopic maternal refractive errors (P < 0.001; B: 0.18; 95%CI: 0.12, 0.24), and fewer hours spent outdoors (P = 0.038; B: 0.18; 95%CI: 0.01, 0.35). The prevalence of myopia, defined as refractive errors (spherical equivalent) of ≤-0.50, ≤-1.00, and ≤-6.00 D in the worse eye, was 60.0 ± 1.2%, 48.0 ± 1.3%, and 2.9 ± 0.4%, respectively. The prevalence of high myopia (≤-6.00 D) was 2.9 ± 0.4% in the whole study population, and it was 9.9 ± 3.0% in 17-year-olds. It was not associated with time spent outdoors (P = 0.66). CONCLUSIONS: Even in Western China, prevalence of myopia in schoolchildren is high. As in East China, low and medium myopia was associated with less time spent outdoors. High myopia was not significantly associated with outdoors time. Compared with the myopia prevalence in elderly Chinese populations, the relatively high myopia prevalence in schoolchildren in China predicts a marked increase in vision-threatening high myopia in future elderly populations in China.

Intraocular pressure and associations in children. The Gobi Desert Children Eye Study.

PURPOSE: To assess the intraocular pressure (IOP) and its association in children in a population living in an oasis in the Gobi Desert. METHODS: The cross-sectional school-based study included all schools in the Ejina region. The children underwent an ophthalmic examination, non-contact tonometry and measurement of blood pressure and body height and weight. RESULTS: Out of eligible 1911 children, 1565 (81.9%) children with a mean age of 11.9±3.5 years (range: 6-21 years) participated. Mean spherical refractive error was -1.58±2.00 diopters. In multivariate analysis, higher IOP (right eye) was associated with younger age (P<0.001; standardized coefficient beta: -0.13; regression coefficient B: -0.13; 95% Confidence interval (CI):-0.18, -0.07), higher diastolic blood pressure (P<0.001;beta:0.13;B:0.05;95%CI:0.03,0.07), higher corneal refractive power (P<0.001;beta:0.11;B:0.23;95%CI:0.12,0.34), more myopic refractive error (P = 0.035;beta: -0.06;B: -0.10;95%CI: -0.19, -0.001), and Han Chinese ethnicity of the father (P = 0.03;beta:0.06;B:0.42;95%CI:0.04,0.89). If age and diastolic blood pressure were dropped, higher IOP was associated with higher estimated cerebrospinal fluid pressure (CSFP) (P<0.001;beta:0.09; B:0.13;95%CI:0.06,0.21) after adjusting for higher corneal refractive power (P<0.001) and Han Chinese ethnicity of the father (P = 0.04). Correspondingly, higher IOP of the left eye was associated with younger age (P<0.001;beta: -0.15;B: -0.16;95%CI: -0.21, -0.10), female gender (P<0.001;beta:0.09;B:0.65;95%CI:0.30,1.01), higher corneal refractive power (P<0.001;beta:0.08;B:0.19;95%CI:0.06,0.32), more myopic refractive error (P = 0.03;beta: -0.06;B: -0.12;95%CI: -0.22, -0.01), and higher estimated CSFP (P<0.001;beta:0.11;B:0.17;95%CI:0.09,0.24). CONCLUSIONS: In school children, higher IOP was associated with steeper corneal curvature and with younger age and higher blood pressure, or alternatively, with higher estimated CSFP. Corneal curvature radius should be included in the correction of IOP measurements. The potential association between IOP and CSFP as also assumed in adults may warrant further research.