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| 1 | An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma显示文摘No clinically available biomarkers can predict pathological complete response(pCR)for esophageal squamous cell carcinomas(ESCCs)with neoadjuvant chemoradiotherapy(nCRT).Considering that antitumor immunity status is an important determinant for nCRT,we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis.During the discovery phase,14 differentially expressed immune-related genes(DEIGs)with greater than a twofold change between pCRs and less than pCRs( | Chaoqi Zhang Guochao Zhang Nan Sun Zhen Zhang Liyan Xue Zhihui Zhang Haijun Yang Yuejun Luo Xiaoli Zheng Yonglei Zhang Yufen Yuan Ruixue Lei Zhaoyang Yang Bo Zheng Le Wang Yun Che Feng Wang Sihui Wang Shugeng Gao Qi Xue Yi Zhang Jie He | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 2 | Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity显示文摘Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research. | Xuanming Chen Cheng Shen Zhe Wei Rui Zhang Yongsheng Wang Lili Jiang Ke Chen Shuang Qiu Yuanli Zhang Ting Zhang Bin Chen Yanjun Xu Qiyi Feng Jinxing Huang Zhihui Zhong Hongxia Li Guowei Che Kai Xiao | 2021 | Cancer Biology & Medicine2021，18，1： | 5 |
| 3 | ASB3 knockdown promotes mitochondrial apoptosis via activating the interdependent cleavage of Beclin1 and caspase-8 in hepatocellular carcinoma显示文摘Apoptosis and autophagy are distinct cellular processes that can be highly interconnected. The cross talk between the two processes is indispensable in determining the overall cell fate. Although the apoptosis-promoting effect of caspases has been demonstrated, the roles of autophagy-related proteins and even autophagy itself in regulating apoptosis remain poorly understood. In our present study, we found that downregulation of ubiquitin E3 ligase ASB3 led to enhanced mitochondrial apoptosis as well as autophagy, which synergistically promoted cell death in hepatocellular carcinoma(HCC). We observed the activation of caspase-8 and decrease of autophagy protein Beclin1 in apoptotic cells that were depleted of ASB3. Beclin1 was mainly cleaved by activated caspase-8 and active Beclin1 initiated mitochondrial apoptosis via locating its C-terminal fragment to mitochondria. In addition, knocking down of Beclin1 markedly blocked the apoptosis, indicating its essential role in the process.Notably, our study indicated that enhanced autophagy level might be involved in the activation of caspase-8 and promote the apoptosis. Taken together, our results demonstrated that ASB3 can regulate mitochondrial pathway of apoptosis by controlling caspase-8 mediated cleavage of Beclin1 in HCC. Therefore, ASB3 may potentially serve as a novel target for HCC therapy,especially when combined with autophagy agonist. | Wenli Zhang Fuchen Liu Zhihui Che Mengmeng Wu Zihui Tang Jie Liu Dongqin Yang | 2019 | Science China(Life Sciences)2019，62，12： | 3 |
| 4 | The combination of novel immune checkpoints HHLA2 and ICOSLG:A new system to predict survival and immune features in esophageal squamous cell carcinoma显示文摘Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC. | Chaoqi Zhang Feng Wang Nan Sun Zhen Zhang Guochao Zhang Zhihui Zhang Yuejun Luo Yun Che Hong Cheng Jiagen Li Jie He | 2022 | Genes & Diseases2022，9，2： | 0 |
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