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iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnosticbiomarker of colorectal cancer

null

《医学前沿（英文）》 2016年 第10卷 第3期   页码 278-285 doi: 10.1007/s11684-016-0453-z

摘要：

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. We aimed to find novel molecules as potential biomarkers for the early diagnosis of CRC. A serum-free conditioned medium was successfully collected from three pairs of CRC tissue and adjacent normal tissue. iTRAQ-based quantitative proteomic analysis was applied to compare the differences in secretome between primary CRC mucosa and adjacent normal mucosa. A total of 145 kinds of proteins were identified. Of these proteins, 29 were significantly different between CRC and normal tissue. Tropomyosin 2 β (TPM2) exhibited the most significant differences; as such, this protein was selected for further validation. Quantitative real-time PCR indicated that the mRNA expression of TPM2 significantly decreased in the CRC tissue compared with the paired adjacent normal tissue. Immunohistochemical analysis also confirmed that TPM2 was barely detected at protein levels in the CRC tissue. In summary, this study revealed potential molecules for future biomarker applications and provided an efficient approach for the differential analysis of cancer-associated secretome. TPM2 may be valuable for the early diagnosis of CRC.

关键词： iTRAQ     secretome     colorectal cancer     TPM2    

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Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

《医学前沿（英文）》 2019年 第13卷 第1期   页码 83-93 doi: 10.1007/s11684-019-0682-z

摘要：

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%–85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

关键词： S492R EGFR ectodomain mutation     colorectal cancer     mAb CH12     immunnotherapy    

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Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2019年 第13卷 第4期   页码 461-470 doi: 10.1007/s11684-019-0695-7

摘要： The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal–luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in which is a butyrate-producing genera of bacteria, and a significant increase in in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to and may serve as a promising biomarker for the early detection of CRC.

关键词： colorectal cancer (CRC)     gut microbiota     intestinal     Eubacterium     Devosia    

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肠道不同解剖部位的菌群组成及其在结直肠癌中的作用

赵浏阳, 张翔, 左涛, 于君

《工程（英文）》 2017年 第3卷 第1期   页码 90-97 doi: 10.1016/J.ENG.2017.01.012

摘要：

结直肠癌是由遗传突变、表观遗传改变、慢性炎症、饮食和生活方式等多因素引起的多阶段疾病。最新研究表明，肠道菌群是结直肠癌发展过程中的重要参与者。肠道菌群稳态的失调，可通过诱发炎症、调控宿主防御、氧化应激和改变细菌代谢产物等机制促进结直肠癌的发生发展。值得注意的是，肠道横、纵截面上不同解剖部位的驻留菌群有所不同。根据细菌在肠道中定植部位的不同，可将其划分为4 种类型：肠腔共生菌、肠黏膜驻留菌、上皮驻留菌和淋巴组织驻留菌。由于结肠共生细菌的易位与结直肠癌的发展密切相关，结直肠癌相关细菌可有望成为用于结直肠癌诊断的非侵入且准确性高的新型生物标志物。本文旨在总结和概述肠道不同解剖部位中的肠道菌群在结直肠癌发生发展中的作用。

关键词： 菌群     结直肠癌     肠腔共生菌     易位     生物标志物    

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结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性 Article

Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer

《工程（英文）》 2023年 第26卷 第7期   页码 32-43 doi: 10.1016/j.eng.2022.08.016

摘要：

Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC tumor and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.

 

关键词： 结直肠癌     肿瘤     多孔石墨化碳液相色谱-质谱     N-糖组     抗体反应    

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结直肠癌黏膜组织来源的大肠杆菌菌株间遗传和功能差异研究 Article

常宇骁, 李享, 丁磊, 杨超, 潘志远, 韩妮, 崔玉军, 智发朝, 杨瑞馥, 高宏,毕玉晶

《工程（英文）》 2022年 第16卷 第9期   页码 210-219 doi: 10.1016/j.eng.2021.03.028

摘要：

结直肠癌是全球第三大癌症。宏基因组学已被广泛用于基于细菌属或种水平的比较来分析肠道微生物群与结直肠癌之间的关系，为结直肠癌发展中的生态失调提供了证据。然而，这种分析并不能为我们提供菌株水平的信息，进而理解一种细菌在结直肠癌发生发展中菌株水平的作用。本文利用培养组学方法分离结直肠癌黏膜样本，并选择了158株大肠杆菌，通过系统发育分析和炎症诱导实验，揭示它们在基因组学和功能上的差异。基因组比较可以将这些菌株分为5个系统群。选择代表性菌株进行THP-1细胞（人白血病单核细胞）Transwell实验以及动物实验，结果显示不同菌株经刺激后，细胞因子水平有显著性差异。进一步的生物信息学分析揭示了不同系统群间单核苷酸多态性、基因和代谢途径的不同特征，这些结果有助于了解这些菌株之间的表型差异。细菌菌株在基因组学和功能上的差异表明，菌株水平上的功能差异可以进一步了解宿主与肠道细菌的相互作用机制。

关键词： 结直肠癌     肠道菌群     培养组学     大肠杆菌     菌株水平    

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发生于胃和结直肠的印戒细胞癌的临床特征以及不同部位的转移对预后的预测价值的研究 Article

吴静静, 方戴琼, 满达, 吴文瑞, 王清, 李雅婷, 叶建中, 李兰娟

《工程（英文）》 2020年 第6卷 第9期   页码 1028-1034 doi: 10.1016/j.eng.2020.06.007

摘要：

印戒细胞癌是胃、结直肠肿瘤中恶性程度最高的病理类型之一。本研究分析了印戒细胞癌的转移特性及其对肿瘤特异性生存率的影响。这项研究纳入了4055例在2010—2012年被诊断为胃印戒细胞癌（signet ring cell carcinoma, SRCC）、结直肠印戒细胞癌患者，其中胃印戒细胞癌2905例，结肠印戒细胞癌和直肠印戒细胞癌1150例。所有临床数据来源于癌症监测、流行病学、最终结果登记资料数据库（SEER）。我们通过卡方检验分析在确诊时伴有远处转移的患者及无远处转移的患者的临床特征。同时用Kaplan-Meier、Cox风险比例回归模型分析出现不同部位转移的患者的预后差异。研究发现，在胃印戒细胞癌患者中，远处淋巴结转移是其最常见的转移部位，而出现脑转移的患者其预后最差。而在患有结肠或直肠的印戒细胞癌患者中，肝脏是其最常见的转移部位，而在确诊时出现远处淋巴结转移的患者的拥有最高的死亡率。总之，出现远处转移常常是预后较差的标志之一，我们的研究结果为印戒细胞癌患者的临床随访、预后分析提供一定的建议。

关键词： SEER数据库，生存分析，印戒细胞癌，转移，结直肠癌，胃癌    

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Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

《医学前沿（英文）》 2007年 第1卷 第3期   页码 304-307 doi: 10.1007/s11684-007-0058-7

摘要： The transient transfection of survivin-targeted siRNA to Lovo cells and its influence on the biological features were studied. Two pairs of 19 base pairs (bp) siRNA-specific targeted survivin gene were designed and synthesized by transcription (Survivin-1, Survivin-2). After transient transfection of the two survivin-targeted siRNAs to Lovo cells by Lipofectamine™ 2000, the expression of survivin mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis was detected by flow cytometry and cell proliferation was evaluated by MTT assay. We found that the expression levels of survivin mRNA of the two RNAi groups (Survivin-1 group and Survivin-2 group) respectively decreased by 70% and 39.1% compared with the control Lovo’s. Seventy-two hours after transfection, apoptosis rates of the two RNAi groups were 21.51% and 26.28%, both of which were higher than control Lovo’s (9.03%). The results at 72 h after transfection were that the optical density (OD) at 490 nm of the two RNAi groups was 0.581±0.070 and 0.681±0.104, both of which were much lower than the control Lovo’s (2.060±0.272). Based on the results, we can draw a conclusion that the two survivin-targeted siRNAs successfully suppressed the expression of survivin mRNA, inhibited cell growth and induce cell apoptosis. It provides a powerful evidence for colorectal carcinoma gene therapy.

关键词： control     therapy     influence     Survivin-1     colorectal carcinoma    

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Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

CAO Jie, LI Wanglin, XIA Jie, TANG Weibiao, WANG Hui, CHEN Xiwen, XIAO Huanqing, LI Yuyuan, CHEN Xiaoping, DU Hong, CHEN Shanming

《医学前沿（英文）》 2007年 第1卷 第2期   页码 147-156 doi: 10.1007/s11684-007-0028-0

摘要： The fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in the carcinogenesis of many human tissues, including digestive tract tissues. However, the expression and the role of the FHIT in the initiation and the development of the colorectal cancer (CRC) are poorly understood. We have shown that the FHIT gene exhibits significantly decreased expression in human CRC compared to colorectal adenoma and normal colorectal tissue by tissue microarray (TMA). The positive rate of FHIT gene expression in normal colorectal tissue, adenoma and adenocarcinoma were 93.75%, 68.75% and 46.25%, respectively. We show this decreased expression to be significantly correlated with the progression of colorectal carcinoma (<0.05) as well as with differentiation and lymph node metastasis (<0.05). We detected two somatic alterations in the FHIT gene in human CRC. The presence of this mutation correlated significantly with decreased FHIT expression in the human CRC. In our present study we tested the hypothesis that the decreased FHIT expression resulted in apoptosis inhibition associated with abnormal expression of apoptosis related proteins. To test this hypothesis we did a series of experiments. In the first test, we assessed apoptosis status using a standard TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling) assay by comparing FHIT-positive CRC vs. FHIT-negative CRC. In the second experiment, the protein expression of the FHIT and other apoptosis related proteins (Bax, Bcl-2 and Survivin) were measured in human CRC by TMA. Our combined results demonstrate the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and the up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT is inactivated specifically in human CRC contributing to our understanding of the mechanism of colorectal carcinogenesis.
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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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The first year follow-up after colorectal adenoma polypectomy is important: A multiple-center study in

Qin-Yan GAO, Hui-Min CHEN, Jing-Yuan FANG, Jian-Qiu SHENG, Ping ZHENG, Cheng-Gong YU, Bo JIANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 436-442 doi: 10.1007/s11684-010-0200-9

摘要： The recurrence of colorectal adenoma (CRA) is high. Although there are guidelines for colonoscopy surveillance after polypectomy in other countries, little is known about its recurrence rate and recurrence peak, especially in China. The aim of the present research is to investigate how long after polypectomy follow-up should take and to analyze risk factors of recurrence. 1208 patients who received polypectomies from five clinical research centers in four regions of China (Shanghai, Guangzhou, Nanjing and Beijing) were included. They were divided into 4 groups: group A (follow-up≤1 year after polypectomy), group B (follow-up 2–3 years after polypectomy), group C (follow-up 4–5 years after polypectomy), and group D (follow-up>5 years after polypectomy). The sex, age, adenoma location, size, number, and pathological characteristics were compared. On the whole, the recurrence rate was 59.46% in group A, 61.09% in group B, 78.07% in group C, and 87.12% in group D, which indicated an increased tendency with a prolonged follow-up duration. There was a significant difference between group A and C or D, and between group B and C or D (<0.01), but there was no statistical difference between group A and B. Additionally, the recurrent patients in the first year had a recurrence rate of 97.33% in the first three years (59.46/61.09), which means that the peak of recurrence was almost entirely concentrated in the first year. The recurrence rate was higher in males and the elder. The risk factors included multiple numbers, villous feature, high-grade dysplasia of medium or smaller size and location in the distal colon. In conclusion, the peak of recurrence was almost totally concentrated in the first year; meanwhile, the first year follow-up is of critical importance in China. It may not be necessary to do the follow-up examination during the second and third years, but after three years, another colonoscopy should be undertaken.

关键词： colorectal adenoma     polypectomy     follow-up     recurrence     risk factor    

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转移性结直肠癌治疗模式随时间的变化趋势以及其与患者生存期的关系——一项基于智能大数据平台的回顾性队列研究 Article

王梓贤, 姚逸尘, 麦宗炯, 林武豪, 黄酉生, 金颖, 骆卉妍, 张东生, 王风华, 王峰, 陈功, 丁培荣, 元云飞, 李宇红, 黄金华, 潘志忠, 徐瑞华

《工程（英文）》 2021年 第7卷 第4期   页码 526-533 doi: 10.1016/j.eng.2020.10.017

摘要：

目前，尤其是在国内，仍缺乏大规模的、高质量的转移性结直肠癌（metastatic colorectal cancer, mCRC）真实世界数据。

关键词： 转移性结直肠癌     真实数据证据     治疗模式     生存期     大数据平台    

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

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Metformin for cancer prevention

Yonghua Yang

《医学前沿（英文）》 2011年 第5卷 第2期   页码 115-117 doi: 10.1007/s11684-011-0112-3

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标题 作者 时间 类型 操作

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnosticbiomarker of colorectal cancer

null

期刊论文

Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

期刊论文

Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

期刊论文

肠道不同解剖部位的菌群组成及其在结直肠癌中的作用

赵浏阳, 张翔, 左涛, 于君

期刊论文

结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性

Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer

期刊论文

结直肠癌黏膜组织来源的大肠杆菌菌株间遗传和功能差异研究

常宇骁, 李享, 丁磊, 杨超, 潘志远, 韩妮, 崔玉军, 智发朝, 杨瑞馥, 高宏,毕玉晶

期刊论文

发生于胃和结直肠的印戒细胞癌的临床特征以及不同部位的转移对预后的预测价值的研究

吴静静, 方戴琼, 满达, 吴文瑞, 王清, 李雅婷, 叶建中, 李兰娟

期刊论文

Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

期刊论文

Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

CAO Jie, LI Wanglin, XIA Jie, TANG Weibiao, WANG Hui, CHEN Xiwen, XIAO Huanqing, LI Yuyuan, CHEN Xiaoping, DU Hong, CHEN Shanming

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文

The first year follow-up after colorectal adenoma polypectomy is important: A multiple-center study in

Qin-Yan GAO, Hui-Min CHEN, Jing-Yuan FANG, Jian-Qiu SHENG, Ping ZHENG, Cheng-Gong YU, Bo JIANG,

期刊论文

转移性结直肠癌治疗模式随时间的变化趋势以及其与患者生存期的关系——一项基于智能大数据平台的回顾性队列研究

王梓贤, 姚逸尘, 麦宗炯, 林武豪, 黄酉生, 金颖, 骆卉妍, 张东生, 王风华, 王峰, 陈功, 丁培荣, 元云飞, 李宇红, 黄金华, 潘志忠, 徐瑞华

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文

Metformin for cancer prevention

Yonghua Yang

期刊论文