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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: LPBCLPBC, LPBCnLPBC, nLPBCLPBC, and nLPBCnLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBCLPBC 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.
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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.
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Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells
Qingxin Song,Shanxin Peng,Zhiqing Sun,Xueyuan Heng,Xiaosong Zhu 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.9
Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is commonin glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a formof programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The presentstudy was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide. Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde(MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detectthe production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecularmechanisms. Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, wefound that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied bya decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results alsoshowed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdownby siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells. Conclusion: Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis bytargeting DMT1 expression in glioblastoma cells.
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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.
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