Data from Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data
Alexios MatikasIoannis ZerdesJohn LövrotFrançois RichardChristos SotiriouJonas BerghAntonios ValachisTheodoros Foukakis
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<div>AbstractPurpose:<p>Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer.</p><p><b>Experimental Design:</b> Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed.</p>Results:<p>Of the initial 4,184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI, 15%–33%) in tumor cells and 33% (95% CI, 14%– 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR, 1.63; 95% CI, 1.07–2.46; <i>P</i> = 0.02); there was significant heterogeneity (<i>I<sup>2</sup></i> = 80%, <i>P</i><sub>heterogeneity</sub> < 0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR, 0.82; 95% CI, 0.74–0.90; <i>P</i> < 0.001 for OS) and in basal-like tumors (HR, 0.64; 95% CI, 0.52–0.80; <i>P</i> < 0.001 for OS; <i>P</i><sub>interaction</sub> 0.005).</p>Conclusions:<p>The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like breast cancer. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.</p></div>PsycINFO
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Limited evidence suggests that inherited predisposing risk variants might affect the disease outcome. In this study, we analyzed the effect of genome-wide association studies—identified breast cancer-risk single nucleotide polymorphisms on survival of early-stage breast cancer patients in a Chinese population. This retrospective study investigated the relationship between 21 GWAS-identified breast cancer-risk single nucleotide polymorphisms and the outcome of 1177 early stage breast cancer patients with a long median follow-up time of 174 months. Cox proportional hazards regression models were used to estimate the hazard ratios and their 95% confidence intervals. Primary endpoints were breast cancer special survival and overall survival while secondary endpoints were invasive disease free survival and distant disease free survival. Multivariate survival analysis showed only the rs2046210 GA genotype significantly decreased the risk of recurrence and death for early stage breast cancer. After grouping breast cancer subtypes, significantly reduced survival was associated with the variant alleles of rs9485372 for luminal A and rs4415084 for triple negative breast cancer. Importantly, all three single-nucleotide polymorphisms, rs889312, rs4951011 and rs9485372 had remarkable effects on survival of luminal B EBC, either individually or synergistically. Furthermore, statistically significant multiplicative interactions were found between rs4415084 and age at diagnosis and between rs3803662 and tumor grade. Our results demonstrate that breast cancer risk susceptibility loci identified by GWAS may influence the outcome of early stage breast cancer patients’ depending on intrinsic tumor subtypes in Chinese women.
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Background. In recent years, traditional Chinese exercises (TCEs) have been gradually used to reduce the blood pressure levels of patients with essential hypertension. However, there are several types of TCEs, and there is no comparative study on the antihypertensive effects of various TCEs in patients with essential hypertension. Objective. The objective is to compare the therapeutic effects of Taijiquan (TJQ), Baduanjin (BDJ), Wuqinxi (WQX), and Yijinjing (YJJ) on essential hypertension and provide a reference for clinical treatment and scheme optimization. Methods. The China National Knowledge Infrastructure (CNKI), Wanfang, China Scientific Journal Database, China Biology Medicine database (CBM), PubMed, Embase, Cochrane Library, and Web of Science databases were searched to collect all randomized controlled trials (RCTs) of TCEs in the treatment of essential hypertension. The search time was from the establishment of each database to November 2021. After data extraction and quality evaluation, the network meta-analysis was performed with Stata 16.0 and ADDIS 1.16.8. Results. Finally, 45 RCTs involving 3864 patients were included. Network meta-analysis showed that YJJ had the best effect in reducing systolic blood pressure, and the difference was statistically significant [MD = −14.27, 95% CI = (−20.53∼−8.08), ]. The best probability ranking was YJJ ( ) > TJQ ( ) > WQX ( ) > BDJ ( ). In terms of reducing diastolic blood pressure, the treatment effect of YJJ was the best, and the difference was statistically significant [MD = −7.77, 95% CI (−12.19∼−3.33), ]. The best probability ranking was YJJ ( ) > TJQ ( ) > WQX ( ) > BDJ ( ). Conclusion. The results showed that TCEs significantly reduced systolic and diastolic blood pressure compared with the control group, and YJJ might be the best choice. However, a larger sample, multicenter, double-blinded, high-quality RCTs are needed to make clear conclusions.
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Results of published studies on the association between the miR-146a rs2910164 polymorphism and the risk of hepatocellular carcinoma (HCC) were inclusive. We performed a meta-analysis. A literature research was conducted using PubMed, Cochrane Library, Ovid, Embase, Wanfang and China National Knowledge Infrastructure (CNKI) databases, to identify studies. Statistical analyses were conducted in STATA version 11.0 (Stata Corporation, College station, TX, USA). A total of 12 publications were included in this meta-analysis. The results of this meta-analysis suggested that miR-146a rs2910164 was associated with an increased risk of HCC (OR = 1.09, 95% CI = 1.00-1.19). In sensitivity analysis, the result was still positive when excluding the studies without HWE (OR = 1.12, 95% CI = 1.01-1.23). In conclusion, this meta-analysis suggested a significant association between miR-146a rs2910164 polymorphism and HCC risk.
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Immunohistochemistry has become an important tool in research and in surgical pathology. Rapid growth of a new methods in immunohistochemistry supplement traditional histochemical and histological light microscopy investigations. Immunohistochemistry has given pathologists a chance to location different antigens on the cell surface as well as in the cell compartments. The expression of antigens are mostly influenced by factors connected with tissue processing; fixation and embedding. The aim of present article is to show the role of these factors and their influence on some immunohistochemical staining results. Not all the problems are discussed here, the main goal which authors would like to obtain is to show the way how to solve problems which can occur during immunohistochemical staining procedure. They want also to delineate the importance of standardization in immunohistochemistry to make the results more reliable between different laboratories.
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Objective To discuss the application o immunohistochemistry autostainer in immunohistochemistry.Methods More than 30 kinds of first antibodies of the Pathology Department,such as AAT,CerBb-2,CK,HBcAg,ER,PR,Ki-67,and unified second antibodies were selected.Immunohistochemistry autostainer and manual operation were applied to the staining of the antibodies,and then the results by the above methods were compared.Results The antibodies stained by immunohistochemistry autostainer,gifted with clear background,no edge effect,uniform staining and accurate positive results,were all better than those by manual operation from all aspects.Conclusion Immunohistochemistry autostainer is highly automatic,time-saving,manpower-saving,repeatable and highly standardized.
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Abstract Breast cancer is a frequent female malignant tumor with high mortality and poor prognosis. Peroxidasin like (PXDNL) has many biological functions, including characteristic activity of hormone biosynthesis, host defense, and cell motility. In addition, PXDNL is closely connected with the progression of breast cancer. In this study, we found that PXDNL may be an independent prognostic biomarker of breast cancer. We tested the mRNA expression of PXDNL in breast cancer by detecting The Cancer Genome Atlas (TCGA) database. The chi-squared test was used to evaluate clinical correlation. The receiver operating characteristic (ROC) curves were drawn to evaluate diagnosis potential in breast cancer. Subsequently, survival analyses were performed to identify the relevance between the expression of PXDNL and the overall survival/relapse-free survival of patients with breast cancer. Univariate/multivariate Cox regression model was executed to detect risk factors affecting the prognosis of patients with breast cancer. PXDNL is highly expressed in breast cancer tissues and is related to survival status of patients. The ROC curve showed that PXDNL had beneficial diagnostic ability in breast cancer. Survival analysis indicated that patients with breast cancer with high PXDNL expression generally had decreased overall survival/relapse-free survival. Univariate/multivariate Cox model analyses further suggested an association between PXDNL expression and prognosis of patients with breast cancer. High PXDNL expression is a potential and independent prognostic biomarker in breast cancer.
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