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.

Long Noncoding RNA Signature and Disease Outcome in Estrogen Receptor- Positive Breast Cancer Patients Treated with Tamoxifen

Gen Wang,Xiaosong Chen,Yue Liang,Wei Wang,Yan Fang,Kunwei Shen 한국유방암학회 2018 Journal of breast cancer Vol.21 No.3

Purpose: Recent data have shown that the expression levels of long noncoding RNAs (lncRNAs) are associated with tamoxifen sensitivity in estrogen receptor (ER)-positive breast cancer. Herein, we constructed an lncRNA-based model to predict disease outcomes of ER-positive breast cancer patients treated with tamoxifen. Methods: LncRNA expression information was acquired from Gene Expression Omnibus by re-mapping pre-existing microarrays of patients with ER-positive breast cancer treated with tamoxifen. The distant metastasis-free survival (DMFS) predictive signature was subsequently built based on a Cox proportional hazard regression model in discover cohort patients, which was further evaluated in another independent validation dataset. Results: Six lncRNAs were found to be associated with DMFS in the discover cohort, which were used to construct a tamoxifen efficacy-related lncRNA signature (TLS). There were 133 and 362 patients with TLS high- and low-risk signatures in the discover cohort. Both univariate and multivariate analysis demonstrated that TLS was associated with DMFS. TLS high-risk patients had worse outcomes than low-risk patients, with a hazard ratio of 4.04 (95% confidence interval, 2.83–5.77; p<0.001). Both subgroup analysis and receiver operating characteristic analysis indicated that TLS performed better in lymph node-negative, luminal B, 21-gene recurrence score high-risk, and 70-gene prognosis signature high-risk patients. Moreover, in a comparison of the 21-gene recurrence score and 70-gene prognosis signature, TLS showed a similar area under receiver operating characteristic curve in all patients. Gene Set Enrichment Analysis indicated that TLS high-risk patients showed different gene expression patterns related to the cell cycle and nucleotide metabolism from those of low-risk patients. Conclusion: This six-lncRNA signature was associated with disease outcome in ER-positive breast cancer patients treated with tamoxifen, which is comparable to previous messenger RNA signatures and requires further clinical evaluation.

Chitosan Nerve Grafts Incorporated with SKP-SC-EVs Induce Peripheral Nerve Regeneration

Zhou Xinyang,Yu Miaomei,Chen Daiyue,Deng Chunyan,Zhang Qi,Gu Xiaosong,Ding Fei 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.2

BACKGROUND: Repair of long-distance peripheral nerve defects remains an important clinical problem. Nerve grafts incorporated with extracellular vesicles (EVs) from various cell types have been developed to bridge peripheral nerve defects. In our previous research, EVs obtained from skin-derived precursor Schwann cells (SKP-SC-EVs) were demonstrated to promote neurite outgrowth in cultured cells and facilitate nerve regeneration in animal studies. METHODS: To further assess the functions of SKP-SC-EVs in nerve repair, we incorporated SKP-SC-EVs and Matrigel into chitosan nerve conduits (EV-NG) for repairing a 15-mm long-distance sciatic nerve defect in a rat model. Behavioral analysis, electrophysiological recording, histological investigation, molecular analysis, and morphometric assessment were carried out. RESULTS: The results revealed EV-NG significantly improved motor and sensory function recovery compared with nerve conduits (NG) without EVs incorporation. The outgrowth and myelination of regenerated axons were improved, while the atrophy of target muscles induced by denervation was alleviated after EVs addition. CONCLUSION: Our data indicated SKP-SC-EVs incorporation into nerve grafts represents a promising method for extended peripheral nerve damage repair.

MiR-200c-3p inhibits LPS-induced M1 polarization of BV2 cells by targeting RIP2

Zhao Lei,Liu Xiaosong,Yang Jiankai,Wang Xiaoliang,Liu Xiaomeng,Wu Jianliang,Li Chen,Xu Donggang,Hu Yuhua 한국유전학회 2022 Genes & Genomics Vol.44 No.4

Background: Microglia are important immune cells, which can be induced by lipopolysaccharide (LPS) into M1 phenotype that express pro-inflammatory cytokines. Some studies have shown that microRNAs play critical roles in microglial activation. Objective: This study was designed to investigate the role of miR-200c-3p in regulating inflammatory responses of LPS-treated BV2 cells. Methods: The expression of miR-200c-3p in BV2 cells was detected by real-time PCR. Receptor-interacting protein 2 (RIP2) was predicted as a target gene of miR-200c-3p. Their relationship was verified by dual-luciferase reporter assay. The function of miR-200c-3p and RIP2 in microglial polarization and NF-κB signaling was further evaluated. Results: LPS treatment reduced miR-200c-3p expression in a dose-dependent and time-dependent manner in BV2 cells. LPS treatment increased the expression of M1 phenotype markers inducible nitric oxide synthase (iNOS) and major histocompatibility complex class (MHC)-II, promoted the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and enhanced the nuclear translocation and phosphorylation of nuclear factor-kappaB (NF-κB) p65. Reversely, miR-200c-3p mimics down-regulated the levels of these inflammatory factors. Furthermore, RIP2 was identified to be a direct target of miR-200c-3p. RIP2 knockdown had a similar effect to miR-200c-3p mimics. Overexpression of RIP2 eliminated the inhibitory effect of miR-200c-3p on LPS-induced M1 polarization and NF-κB activation in BV2 cells. Conclusions: MiR-200c-3p mimics suppressed LPS-induced microglial M1 polarization and NF-κB activation by targeting RIP2. MiR-200c-3p/RIP2 might be a potential therapeutic target for the treatment of neuroinflammation-associated diseases.

RNA sequencing reveals lncRNA-mediated non-mendelian inheritance of feather growth change in chickens

Qiu Mohan,Yu Chunlin,Zhu Shiliang,Liu Siyang,Peng Han,Xiong Xia,Chen Jialei,Jiang Xiaosong,Du Huarui,Li Qingyun,Zhang Zengrong,Yang Chaowu 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Long non-coding RNAs (lncRNAs) play an essential role in biological processes. However, the expression patterns of lncRNAs that regulate the non-Mendelian inheritance feather phenotypes remain unknown. Objective: This study aimed to compare the expression profiles of lncRNAs in the follicles of the late-feathering cocks (LC) and late-feathering hens (LH) that followed genetic rules and the early-feathering hen (EH) and early-feathering cock (EC) that did not conform to the genetic laws. Methods: We performed RNA sequencing and investigated the differentially expressed lncRNAs (DElncRNAs) between the early- and late-feathering chickens, which function by cis-acting or participate in the competing endogenous RNA (ceRNA) network. Results: A total of 53 upregulated and 43 downregulated lncRNAs were identified in EC vs. LC, and 58 upregulated and 109 downregulated lncRNAs were identified in EH vs. LH. The target mRNAs regulated by lncRNAs in cis were enriched in the pentose phosphate pathway, TGF-β signaling pathway and Jak-STAT signaling pathway in EC vs. LC and were associated with the TGF-β signaling pathway, Wnt signaling pathway, p53 signaling pathway and Jak-STAT signaling pathway in EH vs. LH. In addition, the lncRNA-mediated ceRNA regulatory pathways of hair follicle formation were mainly enriched in the TGF-β signaling pathway, Wnt signaling pathway, melanogenesis, and calcium signaling pathways. The levels of ENSGALG00000047626 were significantly higher in the late-feathering chickens than in the early-feathering chickens, which regulated the expression of SSTR2 by gga-miR-1649-5p. Conclusion: This study provides a novel molecular mechanism of lncRNA's response to the feather rate that does not conform to the genetic laws in chickens.

Weight Gain during Neoadjuvant Chemotherapy is Associated with Worse Outcome among the Patients with Operable Breast Cancer

Qiong Fang,Jiahui Huang,Lu Gan,Kunwei Shen,Xiaosong Chen,Beiwen Wu 한국유방암학회 2019 Journal of breast cancer Vol.22 No.3

Purpose: This study was aimed at identifying the influence of initial weight and weight change during neoadjuvant chemotherapy (NAC) on pathologic complete response (pCR) and long-term survival in Chinese patients with operable breast cancer. Methods: We conducted a retrospective study using data from 409 female patients who received NAC for stage II or III breast cancer and had complete record of body mass index (BMI) before and after NAC. BMI of < 25 kg/m2 was categorized as normal weight/underweight (NW/UW); 25.0–29.9 kg/m2 was categorized as overweight (OW); ≥30 kg/m2 was categorized as obese (OB). BMI change was defined as the difference in BMI between day 1 of the first cycle of NAC and the day before surgery. A BMI gain or loss of > 2 kg/m2 following NAC was considered to be significant, else was considered stable. The study end points included pCR rates, disease-free survival (DFS), and overall survival (OS). Results: The median follow-up time was 43.2 (8.9–93.6) months. The average BMI was 23.40 ± 3.04 kg/m2 before NAC and 23.66 ± 3.02 kg/m2 after NAC (t = −3.604, p < 0.001). The pCR rate was 25.3% in the NW/UW group and 24.1% in the OW/OB group (p = 0.811), and was similar between the BMI-gain (23.3%) and the BMI-stable/loss (25.1%) groups (p = 0.787). Initial BMI was an independent prognostic factor for DFS (hazard ratio, 1.69; 95% confidence interval [CI], 1.13–2.53; p = 0.011) but not for OS, while BMI-gain was an independent prognostic factor for both DFS (hazard ratio, 2.09; 95% CI, 1.28–3.42; p = 0.003) and OS (hazard ratio, 1.97; 95% CI, 1.04–3.74; p = 0.039). Conclusion: BMI increased after NAC in Chinese breast cancer patients. Initial BMI and BMI change during NAC were not associated with pCR but were reversely associated with survival.

Correlation between Vitamin B12 and Mental Health in Children and Adolescents: A Systematic Review and Meta-analysis

Yongjun Tan,Li Zhou,Kaiqi Gu,Caihong Xie,Yuhan Wang,Lijun Cha,Youlin Wu,Jiani Wang,Xiaosong Song,Xia Chen,Hua Hu,Qin Yang 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.4

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61; 95% confidence interval [95% CI], −2.44 to −0.79; p < 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

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.