Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ER-positive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.

BackgroundThere is a lack of data regarding the prevalence of invasive group B streptococcus (GBS) infection among neonates in China. This study aimed to investigate the incidence and mortality of invasive GBS infection and to identify the risk factors in our hospital.MethodsSeventy-four cases admitted between January 2011 and December 2016 was included in this study. A retrospective matched case-control study was conducted in a tertiary maternity and paediatric hospital. Risk factors for the acquisition of invasive GBS infection and mortality were analysed by univariable and multivariable analysis.ResultsWe collected and analysed data from 74 infants aged < 3 months with invasive GBS infection. Among 67,985 live births, we calculated an incidence of 1.09 per 1000 live births (95%CI:0.81–1.37%); the incidence of Early-onset GBS disease (EOD, n = 65) and Late-onset GBS disease (LOD, n = 9) were 0.96‰(95%CI:0.73–1.19%) and 0.13‰(95%CI:0.04–0.22%), respectively. Overall, pneumonia accounted 63.1% (41/65) of EOD, and sepsis accounted 88.9% (8/9) cases of LOD, respectively. The overall case fatality rate was 8.11% (6/74), including 7.69% (5/65) among cases of EOD and 11.1% (1/9) among cases of LOD. No predictor of mortality was found. Membrane stripping (P = 0.005, aOR: 3.68, 95% CI: 1.48–9.13) and non-resident mother (P < 0.001, aOR: 5.88, 95% CI: 2.36–14.61) were independent risk factors for EOD; no increased risk was found for LOD.ConclusionsThis study demonstrates remarkable country-specific variation in comparison with other countries. Our findings can improve awareness of neonatal GBS infection and lay a cornerstone to ensure accurate representation of the burden.

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