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Lung cancer is the leading cause of cancer-related mortality in men and women globally. Non-small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85-90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and metastasis rates of NSCLC are as high as 30-40% with the 5-year overall survival rate being less than 15%. Therefore, it is necessary to explore the pathogenesis of NSCLC at the genetic level and identify prognostic biomarkers and novel therapeutic targets. Here, we aimed to identify mutated genes with high frequencies in Chinese NSCLC patients using next-generation sequencing and to investigate their relationships with the tumor mutation burden (TMB) and tumor immune microenvironment. A total of 110 NSCLC patients were enrolled to profile the genetic variations. Mutations in EGFR (62.37%), TP53 (61.29%), LRP1B (13.98%), FAT1 (12.90%), KMT2D (11.83%), CREBBP (10.75%), and RB1 (9.68%) were most prevalent. TP53, LRP1B, KMT2D, and CREBBP mutations were all significantly associated with high TMB (P 0.05 or P 0.01). The infiltrating levels of immune cells and immune molecules were enriched significantly in the LRP1B mutation group. LRP1B mutations significantly correlated with stimulating and inhibitory immunoregulators. Gene set enrichment analysis revealed that cell cycle, the Notch signaling pathway, the insulin signaling pathway, and the mTOR signaling pathway are related to LRP1B mutations in the immune system. LRP1B mutations may be of clinical importance in enhancing the anti-tumor immune response and may be a promising biomarker for predicting immunotherapy responsiveness.

BACKGROUND: Invasive breast cancer is a highly heterogeneous tumor, although there have been many prediction methods for invasive breast cancer risk prediction, the prediction effect is not satisfactory. There is an urgent need to develop a more accurate method to predict the prognosis of patients with invasive breast cancer. OBJECTIVE: To identify potential mRNAs and construct risk prediction models for invasive breast cancer based on bioinformatics METHODS: In this study, we investigated the differences in mRNA expression profiles between invasive breast cancer and normal breast samples, and constructed a risk model for the prediction of prognosis of invasive breast cancer with univariate and multivariate Cox analyses. RESULTS: We constructed a risk model comprising 8 mRNAs (PAX7, ZIC2, APOA5, TP53AIP1,MYBPH, USP41, DACT2, and POU3F2) for the prediction of invasive breast cancer prognosis. We used the 8-mRNA risk prediction model to divide 1076 samples into high-risk groups and low-risk groups, the Kaplan-Meier curve showed that the high-risk group was closely related to the poor prognosis of overall survival in patients with invasive breast cancer. The receiver operating characteristic curve revealed an area under the curve of 0.773 for the 8 mRNA model at 3-year overall survival, indicating that this model showed good specificity and sensitivity for prediction of prognosis of invasive breast cancer. CONCLUSIONS: The study provides an effective bioinformatic analysis for the better understanding of the molecular pathogenesis and prognosis risk assessment of invasive breast cancer.

Although the emergence of new treatments has improved the prognosis of women with lung adenocarcinoma (LUAD), the emergence of drug resistance limits their clinical efficacy. Therefore, there is an urgent need to identify new targets and develop a risk scoring system to evaluate the prognosis of patients. 6-methyladenine (M6A), as the most common methyl modification in RNA modification, its clinicopathological features, diagnosis and prognostic value in lung cancer, especially in LUAD remain to be discussed. We analyzed the clinical and sequencing data of the female LUAD cohort from The Cancer Genome Atlas (TCGA), evaluated the expression profiles of 16 M6A regulation-related genes in the cohort and the relationships between genetic changes and clinical characteristics, developed an M6A-related risk scoring system using Cox analysis. Finally, the copy number variations (CNVs) of the related genes in the samples were analyzed and verified using the cBioPortal platform. Compared with other clinical factors, this risk scoring system showed a higher predictive sensitivity and specificity. The M6A-related risk scoring system developed in this study may help to improve the screening of female patients at high risk of LUAD and provides important theoretical bioinformatics support for evaluating the prognosis of such patients.

Breast cancer (BRCA) has traditionally been considered as having poor immunogenicity and is characterized by relatively low tumor mutational burden (TMB). Improving immunogenicity may improve the response to clinical immunotherapy of BRCA. However, the relationship between TMB, immune infiltration, and prognosis in BRCA remains unclear. We aimed to explore their interrelations and potential biomarkers. In this study, based on somatic mutation data of BRCA from The Cancer Genome Atlas (TCGA), patients were categorized into high and low TMB groups utilizing the TMB values. CIBERSOFT algorithm indicated significant infiltration of activated partial immune cells in high TMB group. Besides, ADRB1 had been identified as a prognosis-related immune gene in the mutant genes by the combination of the ImmPort database and the univariate Cox analysis. ADRB1 mutation was associated with lower TMB and manifested a satisfactory clinical prognosis. Various database applications (Gene Set Enrichment Analysis, Tumor IMmune Estimation Resource, Connectivity Map, KnockTF) supported the selection of treatment strategies targeting ADRB1. In conclusion, TMB was not an independent prognostic factor for BRCA and high TMB was more likely to activate a partial immune response. ADRB1 was identified as a potential biomarker and may provide new insights for co-therapy of BRCA.

Triple-negative breast cancer (TNBC) presented as high heterogeneous immunogenicity that lacks useful clinical signatures to risk-stratify immune-benefit subtypes. We hypothesized that molecular-based phenotypic characterization of TNBC tumors and their immunity may overcome these challenges. We enrolled 1,145 patients with TNBC for analysis. Through combining algorithm integration analysis and TNBC datasets, a tumor immune risk score (TIRS) panel consisting of 8 potential biomarkers was identified. The TIRS panel represented excellent effectiveness as an independent predictor. High- and low risk stratification of patients was further achieved by TIRS, and significant survival and immune-infiltration pattern differences were found in each cohort, both at the transcriptome and protein levels. Non-negative matrix factorization clustering further identified four different tumor immune microenvironment types (TIMTs), among which TIMT-II was associated with the best prognosis and immune status, whereas TIMT-IV had the opposite effect, TIMT-III was associated with highly unstable genomes, and TIMT-I displayed stem-cell-related characteristics along with high stromal scores and may have extensive enrichment of tumor-associated fibroblasts and vascular cells. In conclusion, our TIRS panel could serve as a robust prognostic signature and provide therapeutic benefits for immunotherapy. Additionally, coordinating four TIMTs may be helpful for clinical decision-making in TNBC patients.

The relationship between age and breast cancer is ambiguous. Here, we analyzed the differential expression pattern of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in different age groups to provide an effective association between age and breast cancer risk at the molecular level. We integrated the microarray information from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. The patients were divided into young ( < 50 years) and old ( ≥ 50 years) age groups and evaluated by differential gene expression, weighted gene correlation network analysis (WGCNA), functional enrichment analyses, and coexpression analysis. To determine their potential clinical significance, univariate Cox regression analysis and survival assessment were conducted. We identified two lncRNAs (AL139280.1 and AP000851.1) and three mRNAs (MT1M, HBB, and TFPI2) as the risk markers, and Gene set enrichment analysis (GSEA) focusing on a single gene revealed that "pyrimidine metabolism," "cell cycle," and "P53 signaling pathway" were coenriched. These data demonstrated that age may be a risk factor for breast carcinogenesis and prognosis and provide an in-depth molecular characterization based on the expression patterns of lncRNAs and mRNAs.

Background With the development in research, the importance of microRNAs (miRNAs) in the occurrence and metastasis, and prognosis of lung squamous cell carcinoma (LUSC) have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics. Materials and methods We downloaded miRNA and messenger RNA samples related to LUSC from The Cancer Genome Atlas (TCGA) database. Following initial data screening and preprocessing, we utilized the R platform and a range of analysis tools (miRDB, TargetScanHuman7.2, DAVID, and Cytoscape_v3.5.1) to analyze the TCGA data and identify highly specific and sensitive biomarkers. Results We finally identified 12 miRNAs and six central genes closely related to the overall survival of patients with LUSC. We found that high expression of 7 miRNAs (miR-301b, miR-383, miR-512, miR-515, miR-525, miR-577, and miR-5682) and low expression of five miRNAs (miR-448, miR-486, miR-4732,miR-4732, miR-516, and miR-1911) can significantly improve the overall survival rate of patients with LUSC. The six central genes DLGAP5, CENPA, CHEK1, LRRK2, CALB1, and TOP2A are directly or indirectly involved in the formation and metastasis of LUSC and could, therefore, be considered as target genes for drug therapy. Conclusion With the development in research, the importance of miRNAs in the occurrence and metastasis and prognosis of LUSC have received extensive attention. This study aims to identify new biomarkers and pivotal genes associated with LUSC prognosis through bioinformatics.

Advances in cancer biology have allowed early diagnosis and more comprehensive treatment of breast cancer (BC). However, it remains the most common cause of cancer death in women worldwide because of its strong invasiveness and metastasis. In‐depth study of the molecular pathogenesis of BC and of relevant prognostic markers would improve the quality of life and prognosis of patients. In this study, bioinformatics analysis of SNP‐related data from BC patients provided in the TCGA database revealed that six mutant genes (NCOR1, GATA3, CDH1, ATM, AKT1, and PTEN) were significantly associated with the corresponding expression levels of the proteins. The proteins were involved in multiple pathways related to the development of cancer, including the PI3K‐Akt signaling pathway, pertinent microRNAs, and the MAPK signaling pathway. In addition, overall survival and recurrence‐free survival analysis revealed the close associations of the expression of GATA3, NCOR1, CDH1, and ATM with survival of BC patients. Therefore, detecting these gene mutations and exploring their corresponding expression could be valuable in predicting the prognosis of patients. The results of the high‐throughput data mining provide important fundamental bioinformatics information and a relevant theoretical basis for further exploring the molecular pathogenesis of BC and assessing the prognosis of patients.

Cryptotanshinone (IUPAC name: (R)-1,2,6,7,8,9-hexahydro-1,6,6-trimethyl-phenanthro(1,2-b)furan-10,11-dione), a biologically active constituent extracted from the roots and rhizomes of the plant Salvia miltiorrhiza, has been studied in depth as a medicinally active compound and shown to have efficacy in the treatment of numerous diseases and disorders. In this review, we describe in detail the current status of cryptotanshinone research, including findings relating to the structure, pharmacokinetics, pharmacological activity, and derivatives of this compound. Cryptotanshinoneh as a diverse range of pharmacological effects, including anti-cancer, anti-inflammatory, immune regulatory, neuroprotective, and anti-fibrosis activities. Studies on the molecular mechanisms underlying the activities of cryptotanshinone have established that the JAK2/STAT3, PI3K/AKT, NF-κB, AMPK, and cell cycle pathways are involved in the inhibitory and pro-apoptotic effects of cryptotanshinone on different tumor cell lines, these molecular pathways interact in a coordinated manner to inhibit cell proliferation, migration and invasion,and induce transformation, autophagy, necrosis, and cellular immunity. The anti-inflammatory mechanisms of cryptotanshinone have been found to be associated with the TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways, whereasthe Hedgehog, NF-κB, and Nrf-2/HO-1 pathways are regulated by cryptotanshinone to reduce organ fibrosis, and its inhibitory effects on the PI3K/AKT-eNOS pathway have been linked to neuroprotective effects. Given the potential medicinal utility of cryptotanshinone, further research is needed to verify the efficacy and safety of this compound in clinical use, evaluate its pharmacological activity, and identify molecular targets.

Abstract Background: As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial anti-tumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored. Methods: We used cell proliferation assay, scratch and transwell experiments, and cell cycle and apoptosis analyses to observe the intervention effect of podophyllotoxin on breast cancer. Furthermore, we analyzed the differences between GSE31448, GSE65194, and GSE45827 in the Gene Expression Omnibus database (GEO) and explored the differential genes using a STRING database. Centiscape2.2，MCODE cluster analysis and KEGG pathway analysis were used to identify the most significant gene differences. Next, we utilized BATMAN-TCM and TCMSP databases for further screening to identify key genes. Finally, quantitative RT-PCR (qRT-PCR) and Western Blotting were performed to detect the expression of key targets. Results: Our research confirmed that podophyllotoxin could not only inhibit the migration and invasion of triple-negative breast cancer but also affect the cell cycle and induce apoptosis. In total, 566 differential genes were obtained by using the GEO database. After topological network analysis, cluster analysis, and molecular docking screening, we finally identified PLK1, CCDC20, and CDK1 as key target genes. The results of the qRT-PCR assay showed that the mRNA levels of PLK1, CDC20, and CDK1 decreased, while the expression of upstream P53 increased, after drug induction. The Gene Set Enrichment Analysis (GSEA) and co-network analysis showed that PLK1 is a more critical regulatory factor. Further Western Blotting analysis revealed that there was a negative regulatory relationship between the key gene PLK1 and P53 on the protein level. The results were presented as the mean ± standard deviation of triplicate experiments and P

Background As one of the many breast cancer subtypes, human epidermal growth factor receptor 2 (Her2)-positive breast cancer has higher invasiveness and poor prognosis, although the advent of anti-Her2 drugs has brought good news to patients. However, the emergence of drug resistance still limits its clinical efficacy, so there is an urgent need to explore new targets and develop a risk scoring system to improve treatments and evaluate patient prognosis. Methods Differentially expressed mRNAs associated with Her2-positive breast cancer were screened from a TCGA cohort. The prognostic risk scoring system was constructed according to univariate and Lasso Cox regression model analyses and combined with clinical factors (such as age and TNM) for univariate and multivariate analyses to verify the specificity and sensitivity of the risk scoring system. Finally, based on correlation and CNV mutation analyses, we explored the research value of the mRNAs involved in the system as key genes of the model. Results In this study, six mRNAs were screened and identified to construct a prognostic risk scoring system, including four up-regulated mRNA (RDH16, SPC25, SPC24, and SCUBE3) and two down-regulated mRNA (DGAT2 and CCDC69). The risk scoring system can divide Her2-positive breast cancer samples into high-risk and low-risk groups to evaluate patient prognosis. In addition, whether through the time-dependent receiver operating characteristics curve or compared with clinical factors, the risk scoring system showed high predictive sensitivity and specificity. Moreover, some CNV mutations in mRNA increase patient risk by influencing expression levels. Conclusion The risk scoring system constructed in this study is helpful to improve the screening of high-risk patients with Her2-positive breast cancer and is beneficial for implementing early diagnosis and personalized treatment. It is suggested that these mRNAs may play an important role in the progression of Her2-positive breast cancer.

Background. Long noncoding RNAs (lncRNAs) act as competing endogenous RNAs for microRNAs in cancer metastasis. However, the roles of lncRNA-mediated competing endogenous RNA (ceRNA) networks for breast cancer (BC) are still unclear. Material and Methods. The expression profiles of mRNAs, lncRNAs, and miRNAs with BC were extracted from The Cancer Genome Atlas database. Weighted gene coexpression network analysis was conducted to extract differentially expressed mRNAs (DEmRNAs) that might be core genes. Through miRWalk, TargetScan, and miRDB to predict the target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network with BC was constructed. The survival possibilities of mRNAs, miRNAs, and lncRNAs for patients with BC were determined by Kaplan-Meier survival curves and Oncomine. Results. We identified 2134 DEmRNAs, 1059 differentially expressed lncRNAs (DElncRNAs), and 86 differentially expressed miRNAs (DEmiRNAs). We then compose a ceRNA network for BC, including 72 DElncRNAs, 8 DEmiRNAs, and 12 DEmRNAs. After verification, 2 lncRNAs (LINC00466, LINC00460), 1 miRNA (Hsa-mir-204), and 5 mRNAs (TGFBR2, CDH2, CHRDL1, FGF2, and CHL1) were meaningful as prognostic biomarkers for BC patients. In the ceRNA network, we found that three axes were present in 10 RNAs related to the prognosis of BC, namely, LINC00466-Hsa-mir-204-TGFBR2, LINC00466-Hsa-mir-204-CDH2, and LINC00466-Hsa-mir-204-CHRDL1. Conclusion. This study highlighted lncRNA-miRNA-mRNA ceRNA related to the pathogenesis of BC, which might be used for latent diagnostic biomarkers and therapeutic targets for BC.

Recent studies have shown that long noncoding RNAs (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) polymorphisms are associated with cancer susceptibility. The greatest threat to women's health among a variety of cancers is breast cancer (BC), cervical cancer (CC), and ovarian cancer (OC), and the incidence of it is increasing. We performed a meta-analysis to clarify the relationship between lncRNA HOTAIR expression and BC, CC, and OC susceptibility. We thoroughly searched PubMed, Embase, and the Cochrane Library to obtain the relevant literature. We extracted data from case groups and control groups for each single-nucleotide polymorphism (SNP) (rs4759314, rs920778, rs189663, rs12826786, rs7958904, and rs874945) and compared the relationship between alleles, codominance models, dominant and invisible models and BC, CC, and OC susceptibility. Our study included 11 studies with a total of 5322 patients. There was a significant association between the rs4759314 polymorphism of HOTAIR and susceptibility to BC, CC, and OC (codominant model: AG/AA odds ratio [OR] = 1.13 [95% confidence intervals [CI], 1.00-1.29], GG/AA OR = 1.54 [95% CI, 1.06-2.23]; dominant model: GG + AG/AA OR = 1.16 [95% CI, 1.02-1.32]; and recessive model: GG/AA + AG OR = 1.51 [95% CI, 1.05-2.19]). The association between the expression of rs920778 and BC, CC, and OC susceptibility was not clear (alleles T/C: OR = 1.28 [95% CI, 0.87-1.89]; in codominant model: CT/CC OR = 1.10, [95% CI, 0.71-1.71], TT/CC OR = 1.29 [95% CI, 0.59-2.80]; dominant model: TC + TT/CC OR = 1.16, [95% CI, 0.73-1.86]; and recessive model: TT/TC + CC OR = 1.43, [95% CI, 0.83-2.47]). HOTAIR polymorphism rs1899663 was associated with BC, CC, and OC susceptibility to a certain extent, (alleles T/G OR = 0.90 [95% CI, 0.69-1.16]; in the codominant model: GT/GG OR = 0.81 [95% CI, 0.50-1.30], TT/GG OR = 1.04 [95% CI, 0.63-1.72]; dominant model: GT + TT/GG OR = 0.82 [95% CI, 0.52-1.29]; and recessive model: TT/GT + GG OR = 1.21 [95% CI, 0.76-1.94]). The rs12826786, rs7958904, and rs874945 polymorphisms were associated with a certain degree of BC, CC, and OC susceptibility, but they were not statistically significant. HOTAIR rs4759314 increased susceptibility to BC, CC, and OC in some patients; rs029778 and rs1899663 also increased susceptibility to some extent. SNPs rs12826786, rs7958904, and rs874945 did not correlate with an effect on patient susceptibility to BC, CC, and OC.

The risks of gynecologic cancer have not been well established in women with endometriosis. The objective of the present study was to investigate the influence of endometriosis on the risk for three gynecologic cancer (ovarian cancer, endometrial cancer and cervical cancer). We gathered updated evidence about the risk relationship between endometriosis and gynecologic cancers by conducting a comprehensive search of several medical literature electronic databases, including PubMed, Embase and the Cochrane Library. The design and quality of all studies were evaluated using the Newcastle–Ottawa Scale (NOS), and a random-effects model was used to calculate pooled risk ratio (RR). Of the 8538 articles our search produced, we selected 25 qualified studies, including 16 cohort studies and 9 case–control studies. Patients with endometriosis had both an increased risk of ovarian cancer [RR 1.964; 95% CI (1.685, 2.290)]. The risk of endometrial cancer (EC) is not necessarily higher in patients with endometriosis [RR 1.176, 95% CI (0.878, 1.575)]. Endometriosis was not associated with an increased risk for cervical cancer (CC) [RR 0.670, 95% CI (0.537, 0.838)]. Patients with endometriosis need to be closely observed and rechecked regularly to prevent malignant changes.

Recent studies have reported mixed results on the association between the pro-inflammatory dietary index and risk of breast cancer. We perform this comprehensive meta-analysis to figure out whether high dietary inflammatory index (DII) score is a risk factor for the occurrence of breast cancer. We comprehensively searched the PubMed, EMBASE and Cochrane databases to identify included studies updated to September 12, 2017. All studies that reported risk estimates by comparing the highest DII score to the lowest were assessed. A total of seven observational studies were identified: three case controls and four cohorts, involving 319,993 participants. Overall, the meta-analysis reported that individuals with the highest DII score were associated with a 25% increased risk of breast cancer versus those with the lowest DII score (relative risk [RR] = 1.25; 95% confidence interval [CI] 1.09–1.44; I2 = 82.7%, p = 0.000). Upon stratified analysis, significant positive associations remained for postmenopausal women (RR = 1.15; 95% CI 1.02–1.30; p = 0.020), case-control studies (RR = 1.68; 95% CI 1.13–2.49; p = 0.010), Asia (RR = 2.30; 95% CI 1.7–3.12; p = 0.0031) and Europe (RR = 1.26; 95% CI 1.01–1.58; p = 0.0477). When analysed on hormonal receptor status, 36% increased risk was explored for hormone-receptor negative. This meta-analysis suggested that more pro-inflammatory diets (higher DII scores) are associated with increased breast cancer incidence. However, the research is not about significant associations but about moderate effect sizes.

Tingting Zhang,1 Fubin Feng,2 Wenge Zhao,3 Jinhui Tian,4 Yan Yao,3 Chao Zhou,2 Shengjie Dong,5 Congcong Wang,6 Chuanxin Zang,1 Qingliang Lv,7 Changgang Sun2,8 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, WeiFang, China; 2Department of Oncology, Weifang Traditional Chinese Hospital, WeiFang, China; 3Department of Oncology, Clinical Medical Colleges, Weifang Medical University, WeiFang, China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; 5Department of the Joint and Bone Surgery, Yantaishan Hospital, Yantai, China; 6Department of Oncology, Zibo Maternal and Child Health Hospital, Zibo, China; 7Department of Radiology, Weifang people’s Hospital, WeiFang, China; 8Department of Oncology, Affiliated Hospital of Weifang Medical University, WeiFang, China Background: Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. Materials and methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression. Results: A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33–0.58; HR=0.56, 95% CrI: 0.45–0.68; HR=0.45, 95% CrI: 0.32–0.61; HR=0.58, 95% CrI: 0.42–0.81; HR=0.50, 95% CrI: 0.37–0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72–1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83–2.02). Conclusion: Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR. Keywords: first-line endocrine therapy, progression-free survival, objective response rate, advanced breast cancer, network meta-analysis, randomized controlled trial

Wenge Zhao,1,* Chuanxin Zang,2,* Tingting Zhang,2 Jia Li,1 Ruijuan Liu,3 Fubin Feng,3 Qingliang Lv,4 Liang Zheng,5 Jinhui Tian,6 Changgang Sun3 1Department of Oncology, College of Clinical Medicine, Weifang Medical University, Weifang, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 3Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, People’s Republic of China; 4Department of Interventional Radiology, Weifang People’s Hospital, Weifang, People’s Republic of China; 5Department of Cardiovascular Medicine, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 6Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Background: The clinicopathological and prognostic values of the cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) in ovarian cancer (OC) remain unknown. The aim of our meta-analysis was to evaluate ALDH1’s association with clinicopathological characteristics and its prognostic significance in patients with OC. Materials and methods: PubMed, Embase, and China Biology Medicine were systematically searched for eligible studies (up to October 2017). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% CIs were used to evaluate the association of ALDH1 expression with clinicopathological features and survival outcomes. Results: A total of 17 papers (18 studies) that included 2,531 patients with OC were analyzed. The results showed a significant association between increasing ALDH1 expression and International Federation of Gynecology and Obstetrics stage (OR 2.02, 95% CI 1.16–3.52), lymph node metastasis (OR 1.91, 95% CI 1.01–3.61), and distant metastasis (OR 5.43, 95% CI 1.44–20.42) in OC. However, no significant correlation was found between increasing ALDH1 expression and age (OR 0.90, 95% CI 0.25–3.28), tumor size (OR 1.13, 95% CI 0.75–1.71), tumor location (OR 0.69, 95% CI 0.22–2.13), ascite status (OR 0.74, 95% CI 0.49–1.11), resistance status (OR 0.70, 95% CI 0.14–3.51), or clinicopathological type (OR 1.14, 95% CI 0.69–1.86). Moreover, a high ALDH1 expression was significantly associated with overall survival (HR 1.56, 95% CI 1.21–2.02) but not with disease-free survival (HR 1.38, 95% CI 0.99–1.93). Conclusion: The meta-analysis indicates that increasing ALDH1 predicts poor prognosis and clinicopathological characteristics in OC. Future studies are needed to explore tailored treatments that directly target ALDH1 for the improvement of survival in OC. Keywords: ovarian cancer, ALDH1, prognosis, clinicopathological characteristics, meta-analysis

Background: Trastuzumab remains the standard protocol recommended for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). After disease progression, the decision to continue trastuzumab treatment in combination with another type of chemotherapy, or to replace it with another HER2-targeted therapy, has not been conclusive. Methods: We systematically searched databases and extracted data from randomized controlled trials (RCTs) on patients who experienced disease progression after receiving trastuzumab-based therapies. Paired meta-analyses were performed to provide a comparison between patients continuously received trastuzumab-based therapy and those receiving other targeted therapies. Bayesian network meta-analysis was used to synthesize available evidence of direct or indirect comparison. Results: The 10 selected articles that included 3,158 patients were analyzed. The paired meta-analysis showed a 29% (hazard ratio (HR): 0.71; 95% confidence interval (CI): 0.60–0.85) reduction in mortality risk for patients continued receiving trastuzumab-based therapy than those receiving other targeted regimen. Bayesian network meta-analysis suggested that pertuzumab and trastuzumab plus capecitabine (PHC) showed an improvement in the overall survival (OS), with the highest surface under the cumulative ranking (SUCRA) (0.962 (82.3%)). In terms of progression-free survival (PFS) and objective response rate (ORR), trastuzumab emtansine (T-DM1) showed the highest SUCRA (0.949 (73.2%) and 0.997 (98.5%), respectively). Conclusions：Continuing trastuzumab with another type of chemotherapy is a better option for patients who experience disease progression after receiving trastuzumab-based therapy. Patients treated with PHC had the highest OS. Meanwhile, patients treated with T-DM1 showed better PFS and ORR than those treated with other regimens.

Background: Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumourigenesis. Methods: We obtained breast cancer genetic data from The Cancer Genome Atlas (TCGA) database, network pharmacology to further clarify its biological properties. Survival analysis and molecular docking techniques were implemented for the final screening to obtain key target information. Our experiments focused on the detection of intervention effects of APS on BC cells (MCF-7 and MDA-MB-231), and quantitative RT-PCR (qRT-PCR) was used to assess the expression of key targets. Results: A total of 1,439 differentially expressed genes (DEGs) were identified by TCGA and used to build disease networks. Module analysis, gene ontology and pathway analysis revealed characteristic of the DEGs network. Topological properties were used to identify key targets, survival analysis and molecular docking finally found that the targets of APS regulation of BC cells may be CCNB1, CDC6 and p53. Through cell viability, migration and invasion assays, we found that APS interferes with the development of breast cancer in MCF7 and MDA-MB-231 cells in a dose-dependent manner. Furthermore, qRT-PCR verification suggested that the expression of CCNB1 and CDC6 in breast cancer cells was significantly downregulated in response to APS, while expression of the tumour suppressor gene P53 was significantly increased. Conclusion: Results of this study suggest therapeutic potential for APS in BC treatment, possibly through interventions with CCNB1, CDC6 and P53. Furthermore, these findings illustrate the feasibility of using network pharmacology to connect large-scale target data as a way to discover the mechanism of natural products interfering with disease.

Long non‐coding RNAs (lncRNAs), which competitively bind miRNAs to regulate target mRNA expression in the competing endogenous RNAs (ceRNAs) network, have attracted increasing attention in breast cancer research. We aim to find more effective therapeutic targets and prognostic markers for breast cancer. LncRNA, mRNA and miRNA expression profiles of breast cancer were downloaded from TCGA database. We screened the top 5000 lncRNAs, top 5000 mRNAs and all miRNAs to perform weighted gene co‐expression network analysis. The correlation between modules and clinical information of breast cancer was identified by Pearson's correlation coefficient. Based on the most relevant modules, we constructed a ceRNA network of breast cancer. Additionally, the standard Kaplan‐Meier univariate curve analysis was adopted to identify the prognosis of lncRNAs. Ultimately, a total of 23 and 5 modules were generated in the lncRNAs/mRNAs and miRNAs co‐expression network, respectively. According to the Green module of lncRNAs/mRNAs and Blue module of miRNAs, our constructed ceRNA network consisted of 52 lncRNAs, 17miRNAs and 79 mRNAs. Through survival analysis, 5 lncRNAs (AL117190.1, COL4A2‐AS1, LINC00184, MEG3 and MIR22HG) were identified as crucial prognostic factors for patients with breast cancer. Taken together, we have identified five novel lncRNAs related to prognosis of breast cancer. Our study has contributed to the deeper understanding of the molecular mechanism of breast cancer and provided novel insights into the use of breast cancer drugs and prognosis.

Fubin Feng,1 Tingting Zhang,2 Fang Yin,3 Cun Liu,2 Jing Zhuang,1 Lingyu Qi,2 Xue Wang,4 Jia Li,5 Lu Wang,1 Jinhui Tian,6 Changgang Sun1,7 1Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, China; 2College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China; 3Department of Pediatrics, Weifang People’s Hospital, Weifang, Shandong Province, China; 4Department of Medicine, Qingdao University, Qingdao, Shandong Province, China; 5Department of Oncology, Weifang Medical University, Weifang, Shandong Province, China; 6Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, China; 7Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, China Purpose: Numerous HER2-targeted therapy clinical trials have demonstrated efficacy and safety in the first-line treatment of metastatic breast cancer (MBC). However, the direct or indirect comparison of these drugs is unclear. This network meta-analysis can solve this issue to some extent. Materials and methods: PubMed, Embase, and the Cochrane Library were searched for Phase II/III randomized controlled trials (RCTs) on metastatic HER2-positive breast cancer for first-line treatment up to December 16, 2017. Paired meta-analyses were performed to compare the regimens directly with the TP (trastuzumab plus taxane) regimen. Bayesian network meta-analysis was used to synthesize available evidence of direct or indirect comparison. Results: The database search identified 1,935 articles, among which 13 articles (10 RCTs) were eligible for the analysis involving 5,177 patients treated with 11 different regimens. The progression-free survival (PFS) in the Bayesian network meta-analysis suggested that the PTP (pertuzumab and trastuzumab plus taxane) regimen had the highest probability to be the preferred treatment (surface under the cumulative ranking [SUCRA]: 0.967) followed by the TPC (carboplatin and trastuzumab plus taxane) regimen (SUCRA: 0.923). The PTP regimen (SUCRA: 0.926) was similarly preferred for overall survival (OS). For objective response rate (ORR), the PTC regimen might be the optimal treatment (SUCRA: 0.935), followed by the PTP regimen. Conclusion: Overall, PTP might be the optimal first-line treatment for HER-2-positive MBC to improve the PFS and OS. Meanwhile, TPC might be most effective treatment in terms of the ORR. Regarding safety, the two regimens showed acceptable grade 3 or greater hematologic toxicity and heart failure. Keywords: breast cancer, metastasis, HER2-positive, HER2-targeted agents, network meta-analysis, randomized controlled trial

Tingting Zhang,1,* Fubin Feng,2,* Wenge Zhao,3 Yan Yao,3 Jinhui Tian,4 Chao Zhou,2 Chuanxin Zang,1 Cun Liu,1 Xue Wang,5 Changgang Sun2,6 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong, People’s Republic of China; 3Clinical Medical College, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 5Medical Colleges, Qingdao University, Qingdao, Shandong, People’s Republic of China; 6Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, People’s Republic of China *These authors contributed equally to this work Background: We performed a network meta-analysis of randomized controlled trials (RCTs) to indirectly compare the efficacy of different targeted agents with fulvestrant for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor type 2-negative (HER2–) advanced breast cancer (ABC) following progression on prior endocrine therapy.Methods: The titles/abstracts were searched from the PubMed, EMBASE, and the Cochrane Library databases for RCTs to evaluate the efficacy of palbociclib plus fulvestrant vs alternative targeted therapies plus fulvestrant for postmenopausal HR+/HER2– ABC following progression on prior endocrine therapy. In addition, the primary measured outcome was progression-free survival (PFS) and objective response rate. The surface under the cumulative ranking (SUCRA) value of each treatment was calculated to achieve the best ranking for each treatment.Results: A total of 11 studies, including 4,178 patients in the network meta-analysis, were included and analyzed. In terms of the pooled hazard ratios (HRs) for PFS, palbociclib plus fulvestrant was superior to other target agents plus fulvestrant (HR=0.62, 95% credible interval [CrI]: 0.40–0.96; HR=0.62, 95% CrI: 0.47–0.96; for pictilisib plus fulvestrant and buparlisib plus fulvestrant, respectively). Ribociclib plus fulvestrant has no difference in abemaciclib plus fulvestrant and palbociclib plus fulvestrant (HR =1.02, 95% CrI =0.72–1.45; HR =1.22, 95% CrI =0.84–1.78). In terms of objective response rate, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, dovitinib plus fulvestrant, buparlisib plus fulvestrant, and palbociclib plus fulvestrant had a significant difference (odds ratio [OR] =2.84, 95% CrI =1.91– 4.31; OR =3.62, 95% CrI =1.21–12.48; OR =1.80, 95% CrI =1.25–2.60; and OR =2.52, 95% CrI =1.43– 4.72, respectively).Conclusion: According to the present study, palbociclib plus fulvestrant may be the optimal treatment for HR+/HER2– postmenopausal women with ABC after disease progression following endocrine therapy. Keywords: advanced breast cancer, endocrine therapy, targeted therapy, progression-free survival, objective response rate, network meta-analysis

Tingting Zhang,1 Yan Yao,2 Fubin Feng,3 Wenge Zhao,2 Jinhui Tian,4 Chao Zhou,3 Xue Wang,5 Shengjie Dong,6 Jia Li,2 Lingyu Qi,7 Changgang Sun3,8 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Clinical Medical College, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, People’s Republic of China; 4Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 5Clinical Medical Colleges, Qingdao University, Shinan District, Qingdao, Shandong Province, People’s Republic of China; 6Department of the Joint and Bone Surgery, Yantaishan Hospital, Yantai, Shandong Province, People’s Republic of China; 7College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan, People’s Republic of China; 8Department of Oncology, Affiliated Hospital of Weifang Medical University, Kuiwen District, Weifang, Shandong Province, People’s Republic of China Background: Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of the efficacy of different chemotherapy regimens in adults with advanced-stage HL.Materials and methods: We searched for relevant randomized controlled trials (RCTs) in titles/abstracts in PubMed, Embase, and the Cochrane Library. The search was last updated on April 3, 2018. RCTs that assessed the effectiveness of one of the following treatments were included: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); four cycles of increased dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) followed by two or four cycles of standard dose of BEACOPP (4× BEACOPPescalated + 2 or 4× BEACOPPbaseline); brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD); doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (Stanford V); mechlorethamine (cyclophosphamide), vincristine, procarbazine, and prednisone (M[C]OPP); sequential or alternating chemotherapy regimens with ABVD as the footstone (eg, COPP/ABVD or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/ABVD); eight cycles of BEACOPPescalated; hybrid MOPP/ABV; and M[C]EC (M[C]OPP with epidoxorubicin, bleomycin, vinblastine [EBV], and lomustine, doxorubicin, and vindesine [CAD]).Results: Overall, we screened 3,564 citations and deemed 18 reports of 16 trials eligible and included them in our network meta-analysis. A total of 11,928 participants were randomly assigned to one of the 12 combinations of chemotherapy regimens, of which 11,476 participants were analyzed. For the overall survival (OS), no differences were observed within any interventions when the ABVD regimen was used as the reference treatment. Similarly, relative to A+AVD, 8× BEACOPPescalated and 6× BEACOPPescalated also showed no differences (HR =1.07, 95% credible interval (CrI): 0.58–1.95; HR =0.62, 95% CrI: 0.16–1.83; and HR =0.71, 95% CrI: 0.30–1.72, respectively). In terms of complete remission (CR), enough evidence exists to support a maximum clinical treatment effect for 6× BEACOPPescalated (OR =1.88, 95% CrI: 1.20–2.96; and OR =3.43, 95% CrI: 1.87–6.24).Conclusion: When compared across the 12 combined chemotherapy regimens, six cycles of BEACOPPescalated may be the optimal treatment for patients with advanced-stage HL. Keywords: advanced-stage Hodgkin lymphoma, combined chemotherapy, overall survival, network meta-analysis, randomized controlled trial

Background The optimal sequence of endocrine therapy in a neoadjuvant setting for hormone receptor-positive (HR+) breast cancer is unclear. Our study evaluated the efficacy and acceptability of neoadjuvant endocrine therapy for HR+ breast cancer. Methods We identified studies based on titles and abstracts that were published before 22 June 2018 in the following databases: PubMed, EMBASE, and the Cochrane Library. Eligible studies were randomised controlled trials with at least one arm that evaluated the effectiveness of one or a combination of anastrozole, letrozole, palbociclib, tamoxifen, fulvestrant, abemaciclib, everolimus, gefitinib, ribociclib, taselisib, and exemestane. We pooled effect sizes using the odds ratio (OR) and corresponding 95% credibility interval (95% CrI). The primary outcomes were response rate and treatment completion. Results Our network meta-analysis included 3,306 participants and 16 eligible studies, which assessed 15 treatments. In terms of response rates, compared with letrozole combined therapy, tamoxifen was associated with a significant reduction in response rate (OR, 0.34; 95% CrI, 0.13-0.85; OR, 0.32; 95% CrI, 0.13-0.80; OR, 0.26; 95% CrI, 0.09-0.83; and OR, 0.30; 95% CrI, 0.09-0.96; for letrozole plus everolimus, letrozole plus taselisib, letrozole plus zoledronic acid, and letrozole plus lapatinib, respectively). Based on the surface under the cumulative ranking curves ranking, letrozole plus zoledronic acid was associated with the highest rate of response (87.6%), followed by letrozole plus lapatinib (85.2%), and letrozole plus taselisib (79.3%). Conclusions Ultimately, our study established that letrozole plus zoledronic acid may be an optimal treatment based on its current rank in a neoadjuvant setting for HR+ breast cancer.

Cun Liu,1 Lu Wang,1 Lijuan Liu,2 Jing Zhuang,2 Shifeng Tang,2 Tiansong Zhang,3 Chao Zhou,2 Fubin Feng,2 Ruijuan Liu,2 Jinmei Zhang,4 Tingting Zhang,1 Chundi Gao,5 Huayao Li,5 Jia Li,6 Changgang Sun2,7 1College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, Shandong Province, People’s Republic of China; 3Department of Traditional Chinese Medicine, Jing’an District Central Hospital, Shanghai, People’s Republic of China; 4Department of Endocrinology, Weifang Traditional Chinese Hospital, Weifang, Shandong, Province People’s Republic of China; 5First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, People’s Republic of China; 6College of Basic Medicine, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 7Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China Background: Compared with application of bone-modifying agents (BMAs) every 4weeks, it is unclear whether 12-weekly de-escalated therapy can be used as a substitute strategy. Methods: A systematic search of PubMed, EMBASE, and the Cochrane Register of Controlled Trials until November 22, 2017, was performed. Randomized controlled trials (RCTs) were included to assess skeletal-related event (SRE) rates, adverse events, and bone turnover biomarkers, comparing 12-weekly de-escalated treatments with standard 4-weekly dosage regimens. Risk ratios (RRs) with 95% CIs were pooled in fixed-effect meta-analyses. Results: A total of eight citations were eligible comprising 2,878 patients: zoledronate (three studies, 2,650 patients), pamidronate (two studies, 68 patients), and denosumab (three studies, 160 patients). Summary RR (0.98; 95% CI 0.87–1.12; P=0.82) for SRE rates between de-escalated and standard arms was produced when seven low risk of bias trials (695 patients) were pooled, and results without statistical significance also appeared in the analysis of adverse events and bone turnover biomarkers. Due to the limited sample size and methodological differences, the data for skeletal morbidity rates (SMRs), time to first SRE, serum C-telopeptide (sCTx) levels, and hypocalcemia were not combined, but systematic review still obtained similar indistinguishableness. Conclusion: In this meta-analysis of randomized clinical trials, the results “appeared” to show non-inferiority of the 12-weekly treatment. Due to the difference in available data, the results for bisphosphonates are more solid than for the receptor activator of nuclear factor-κB ligand (RANKL) antibodies. Keywords: bone-modifying agents, bone metastasis, cancer, de-escalated treatment, meta-analysis

Background Breast cancer (BRCA) is the most prevalent cancer that threatens female health. A growing body of evidence has demonstrated the non-negligible effects of messenger RNAs (mRNAs) on biological processes involved in cancers; however, there is no definite conclusion regarding the role of mRNAs in predicting the prognosis of BRCA patients. Materials and methods We systematically screened the mRNA expression landscape and clinical data of samples from the Cancer Genome Atlas (TCGA). Univariate Cox analysis and robust likelihood-based survival analysis were conducted to identify key mRNAs associated with BRCA. Furthermore, risk scores based on multivariate Cox analysis divided the training set into high-risk and low-risk groups. ROC analysis determined the optimal cut-off point for patient classification of risk levels. The prognostic model was additionally validated in the testing set and complete dataset. Finally, we plotted the survival curves for the mRNAs used in our model. Results We obtained the original expression data of 13,617 mRNAs from a total of 1088 samples. After comprehensive survival analysis, the four-mRNA (ACSL1, OTUD3, PKD1L2, and WISP1) prognosis risk assessment model was constructed. Furthermore, the area under cure (AUC) was 0.834, indicating that the model was meaningful and reasonable. In each dataset, analysis based on the four-mRNA signature risk score indicated that the survival status of the group with high risk score was worse than that of the group with low risk scores. Patients with strong mRNA expression of OTUD3, PKD1L2, and WISP1 tended to have good prognosis, whereas patients with high ACSL1 expression tended to have poor prognosis. Conclusion In summary, we constructed a four-mRNA prognosis risk assessment model for BRCA. The newly developed model offers more possibilities for assessing prognosis and guiding the selection of better treatment strategies for BRCA.

Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis.We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression.A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33-0.58; HR=0.56, 95% CrI: 0.45-0.68; HR=0.45, 95% CrI: 0.32-0.61; HR=0.58, 95% CrI: 0.42-0.81; HR=0.50, 95% CrI: 0.37-0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72-1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83-2.02).Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR.

Currently, research on genome-scale epigenetic modifications for studying the pathogenesis of lung cancer is lacking. Aberrant DNA methylation, as the most common and important modification in epigenetics, is an important means of regulating genomic function and can be used as a biomarker for the diagnosis and prognosis of lung squamous cell carcinoma (LUSC). In this paper, methylation information and gene expression data from patients with LUSC were extracted from the TCGA database. Univariate and multivariate COX analyses were used to screen abnormally methylated genes related to the prognosis of LUSC. The relationship between key DNA methylation sites and the transcriptional expression of LUSC-related genes was explored. A prognostic risk model constructed by four abnormally methylated genes (VAX1, CH25H, AdCyAP1, and Irx1) was used to predict the prognosis of LUSC patients. Also, the methylation levels of the key gene IRX1 are significantly correlated with the prognosis and correlated with the methylation of the site cg09232937 and cg10530883. This study is based on high-throughput data mining and provides an effective bioinformatics basis for further understanding the pathogenesis and prognosis of LUSC, which has important theoretical significance for follow-up studies on LUSC.

// Cun Liu 1, * , Lu Wang 1, * , Jinhui Tian 2 , Lijuan Liu 3 , Linxiang Guo 4 , Guowen Ge 5 , Liang Zheng 6 , Fubin Feng 3 , Jinmei Zhang 7 , Tingting Zhang 1 and Changgang Sun 3, 8 1 College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, PR China 2 Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu, PR China 3 Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261041, Shandong Province, PR China 4 School of Foreign Language Education, Qingdao University, Qingdao 266071, Shandong, PR China 5 Clinical College, Weifang Medical University, Weifang 261000, Shandong, PR China 6 Department of Cardiovascular Medicine, Research Center for Translational Medicine, Dongfang Hospital, Tongji University, Shanghai 200000, PR China 7 Department of Endocrinology, Weifang Traditional Chinese Hospital, Weifang 261041, Shandong, PR China 8 Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong, PR China * These authors contributed equally to this work and are co-first authors Correspondence to: Changgang Sun, email: zhongliuyike@163.com Keywords: breast cancer; Parkinson's disease; meta-analysis; risk Received: October 11, 2017 Accepted: December 05, 2017 Published: January 02, 2018 ABSTRACT Objective: We performed a meta-analysis to explore the association between breast cancer and Parkinson’s disease (PD). Materials and Methods: Specific literature searches were performed systematically using PubMed, Cochrane Library and EMBASE. Studies about the related risk estimates of breast cancer and PD were included in the meta-analysis. Results: A total of 22 sets of research data from 16 studies were analyzed. The combined odds ratio (OR) of the results was 1.13 (95% CI: 1.09–1.17). When stratified by PD diagnosis time, the ORs for the occurrence of breast cancer before and after PD diagnosis were 0.99 (95% CI: 0.89–1.09) and 1.15 (95% CI: 1.10–1.20). Subgroup analysis showed that the ORs for the cohort studies and for Caucasians were 1.13 (95% CI: 1.09,1.08) and 1.13 (95% CI: 1.09–1.17), respectively. No statistically significant risk estimates were found for studies in Asian and mixed populations as well as for case-control studies ( P > 0.05). Conclusions: The current evidence demonstrates a positive correlation between breast cancer and PD, especially following a diagnosis of PD and in Caucasians. Further studies are needed to determine the pathophysiologic mechanisms of this relationship.