Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study

Jiayi Wu,Shuning Ding,Linling Yin,Xiaochun Fei,Caijin Lin,Lisa Andriani,Chihwan Goh,Jiahui Huang,Jin Hong,Weiqi Gao,Siji Zhu,Hui Wang,Ou Huang,Xiaosong Chen,Jianrong He,Yafen Li,Kunwei Shen,Weiguo Che 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Impact of Prior Cancer History on the Clinical Outcomes in Advanced Breast Cancer: A Propensity Score–Adjusted, Population-Based Study

Caijin Lin,Jiayi Wu,Shuning Ding,Chihwan Goh,Lisa Andriani,Kunwei Shen,Li Zhu 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose Despite the rapid growing of cancer survivors, prior cancer history is a commonly adopted exclusion criterion. Whether prior cancer will impact the survival of patients with advanced breast cancer (ABC) remains uncertain. Materials and Methods Patients with ABC diagnosed between 2004 and 2010 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Timing, stage, and type were used to characterize prior cancer. Multivariable analyses using propensity score–adjusted Cox regression and competing risk regression were conducted to evaluate the prognostic effect of prior cancer on overall survival (OS) and breast cancer-specific survival (BCSS). Results A total of 14,176 ABC patients were identified, of whom 10.5% carried a prior cancer history. The most common type of prior cancer was female genital cancer (32.4%); more than half (51.7%) were diagnosed at localized stage; most were diagnosed more than 5 years (42.9%) or less than 1 year (28.3%) prior to the index cancer. In multivariate analyses, patients with prior cancer presented a slightly worse OS (hazard ratio, 1.18; 95% confidence interval [CI], 1.07 to 1.30; p=0.001) but a better BCSS (subdistribution hazard ratio, 0.64; 95% CI, 0.56 to 0.74; p < 0.001). In subset analyses, no survival detriment was observed in patients with prior malignancy from head and neck or endocrine system, at in situ or localized stage, or diagnosed more than 4 years. Conclusion Prior cancer provides an inferior OS but a superior BCSS for patients with ABC. It does not affect the survival adversely in some subgroups and these patients should not be excluded from clinical trials.

Establishment and validation of five autophagy-related signatures for predicting survival and immune microenvironment in glioma

Zhao Zijun,Wu Yue,Wang Zairan,Xu Jiayi,Wang Yizheng,Zhao Zongmao 한국유전학회 2022 Genes & Genomics Vol.44 No.1

Background: Gliomas, especially Glioblastoma multiforme, are the most frequent type of primary tumors in central nervous system. Increasing researches have revealed the relationship between autophagy and tumor, while the molecular mechanism of autophagy in glioma is still rarely reported. Objective: Our research aims to conform the autophagy-related genes (ARGs) implicated in the development and progression of glioma and improve our understanding of autophagy in glioma. Methods: 20 candidate ARGs were screened through the protein-protein interaction network. We also downloaded the publicly accessible glioma data for 665 individuals from TCGA and 970 individuals from CGGA with RNA sequences and clinicopathological information. Subsequently, univariate and multivariate Cox regression analysis identified 5 key ARGs among the 20 candidate genes as key prognostic genes for survival, GSEA and immune response analysis. Results: ATG5, BCL2L1, CASP3, CASP8, GAPDH were identified as key ARGs in our research. Further studies showed that the high-risk population was linked to a dismal prognosis and suggested an immune-inhibitory microenvironment. GSEA results demonstrated that high risk population was closely related to DNA repair, hypoxia pathways, implicated in immunosuppression and carcinogenesis. Through CMap, we finally identified 14 candidate drugs for the ARG high risk population. Conclusions: This study established and verified an ARG risk model, which can serve as an independent predictor for prognosis, reflect on the strength of the immune response and predict the potential drugs in glioma. Our findings offer new understandings of ARG molecular mechanism and promising therapeutic targets for glioma treatment.

Quantifying and Localizing the Mitochondrial Proteome Across Five Tissues in A Mouse Population

Williams, Evan G.,Wu, Yibo,Wolski, Witold,Kim, Jun Yong,Lan, Jiayi,Hasan, Moaraj,Halter, Christian,Jha, Pooja,Ryu, Dongryeol,Auwerx, Johan,Aebersold, Ruedi American Society for Biochemistry and Molecular Bi 2018 Molecular and Cellular Proteomics Vol.17 No.9

<P>We have used SWATH mass spectrometry to quantify 3648 proteins across 76 proteomes collected from genetically diverse BXD mouse strains in two fractions (mitochondria and total cell) from five tissues: liver, quadriceps, heart, brain, and brown adipose (BAT). Across tissues, expression covariation between genes' proteins and transcripts-measured in the same individuals-broadly aligned. Covariation was however far stronger in certain subsets than others: only 8% of transcripts in the lowest expression and variance quintile covaried with their protein, in contrast to 65% of transcripts in the highest quintiles. Key functional differences among the 3648 genes were also observed across tissues, with electron transport chain (ETC) genes particularly investigated. ETC complex proteins covary and form strong gene networks according to tissue, but their equivalent transcripts do not. Certain physiological consequences, such as the depletion of ATP synthase in BAT, are thus obscured in transcript data. Lastly, we compared the quantitative proteomic measurements between the total cell and mitochondrial fractions for the five tissues. The resulting enrichment score highlighted several hundred proteins which were strongly enriched in mitochondria, which included several dozen proteins were not reported in literature to be mitochondrially localized. Four of these candidates were selected for biochemical validation, where we found MTAP, SOAT2, and IMPDH2 to be localized inside the mitochondria, whereas ABCC6 was in the mitochondria-associated membrane. These findings demonstrate the synergies of a multi-omics approach to study complex metabolic processes, and this provides a resource for further discovery and analysis of proteoforms, modified proteins, and protein localization.</P>

Effects of Phytosterol Ester on the Fatty Acid Profiles in Rats with Nonalcoholic Fatty Liver Disease

Lihua Song,Haiyue Zhou,Wenjuan Yu,Xinwen Ding,Li Yang,Jiayi Wu,Chenwei Song 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.2

Both serum and hepatic fatty acid (FA) compositions differ among nonalcoholic hepatic steatosis, nonalcoholic steatohepatitis, and healthy subjects. The severity of the above liver disease is closely associated with the concentration and composition of FAs. Our previous study found that phytosterol ester (PSE) could alleviate hepatic steatosis in nonalcoholic fatty liver disease rats. The aims of this work were to explore the effects of PSE (0.05/100 g·body weight) on FA profiles and the mRNA levels of FA metabolism-related genes. Compared with a high-fat diet alone group, PSE treatment significantly decreased hepatic saturated fatty acid levels (P < .05) and increased monounsaturated fatty acid (especially C16:1 n-7) levels in the liver, serum, and adipose tissue and polyunsaturated fatty acid levels in the serum and liver (P < .05) after 12 weeks of intervention. In particular, PSE treatment increased the level of C22:5 n-3, an FA that was negatively correlated with the degree of hepatic steatosis in the serum, liver, and adipose tissue. The increases in some unsaturated fatty acids are probably related to the upregulation of stearoyl-coenzyme A desaturase-1 and fatty acid desaturase-1.

Changes of Tumor Infiltrating Lymphocytes after Core Needle Biopsy and the Prognostic Implications in Early Stage Breast Cancer: A Retrospective Study

Jiahui Huang,Xiaosong Chen,Xiaochun Fei,Ou Huang,Jiayi Wu,Li Zhu,Jianrong He,Weiguo Chen,Yafen Li,Kunwei Shen 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4

Purpose The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes. Materials and Methods A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with  50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival. Results SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p < 0.001). Younger age (< 60 years, p=0.016) and long surgery time interval (STI,  4 days; p=0.003) were independent factors correlating with higher TILs changes. CNB-LPBC patients showed better breast cancer-free interval (BCFI, p=0.021) than CNB-non-LPBC (CNB-nLPBC) patients. Patients were categorized into four groups according to the LPBC change pattern from CNB to SRS: LPBCLPBC, LPBCnLPBC, nLPBCLPBC, and nLPBCnLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBCLPBC pattern was an independent prognostic factor of worse BCFI (hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.53; p=0.035) compared with other patterns. Conclusion TILs were significantly higher in SRS than in CNB. Higher TILs changes were associated with younger age and long STI. Changing from nLPBC to LPBC after CNB indicated a worse BCFI, which needs further validation.

Surface Modifications of Titanium Dental Implants with Strontium Eucommia Ulmoides to Enhance Osseointegration and Suppress Inflammation

Avery Rui Sun,Qili Sun,Yansong Wang,Liqiu Hu,Yutong Wu,Fenbo Ma,Jiayi Liu,Xiangchao Pang,Bin Tang 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Titanium (Ti) is now widely used as implant material due to its excellent mechanical properties and superior biocompatibilities, while its inert bioactivities might lead to insufficient osseointegration, and limit its performance in dental applications. Methods We introduced a robust and simple approach of modifying titanium surfaces with polysaccharide complexes. Titanium samples were subjected to hydrothermal treatment to create a uniform porous structure on the surface, followed by coating with a bioinspired and self-assembly polydopamine layer. Strontium Eucommia Ulmoides Polysaccharide (EUP-Sr) complexes are then introduced to the polydopamine-coated porous titanium. Multiple morphological and physiochemical characterizations are employed for material evaluation, while cell proliferation and gene expression tests using macrophages, primary alveolar bone osteoblasts, and vascular endothelial cells are used to provide an overall insight into the functions of the product. The significances of statistical differences were analyzed using student’s t-test. Results Microscopic and spectrometric characterizations confirmed that the Ti surface formed a porous structure with an adequate amount of EUP-Sr loading. The attachment was attributed to hydrogen bonding between the ubiquitous glycosidic linkage of the polysaccharide complex and the ring structure of polydopamine, yet the loaded EUP-Sr complex can be gradually released, consequently benefiting the neighboring microenvironment. Cell experiments showed no cytotoxicity of the material, and the product showed promising anti-inflammation, osseointegration, and angiogenesis properties, which were further confirmed by in vivo evaluations. Conclusion We believe the EUP-Sr modified titanium implant is a promising candidate to be used in dental applications with notable osteoimmunomodulation and angiogenesis functions. And the novel technique proposed in this study would benefit the modification of metal/inorganic surfaces with polysaccharides for future research.