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Genomic landscape of T-cell lymphoblastic lymphoma T细胞淋巴母细胞淋巴瘤的基因组景观
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.03
Zhaoming Li, Yue Song, Mingzhi Zhang, Yiming Wei, Hang Ruan
Objective T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm of precursor T cells, however, detailed genome-wide sequencing of large T-LBL cohorts has not been performed due to its rarity. The purpose of this study was to identify putative driver genes in T-LBL. Methods To gain insight into the genetic mechanisms of T-LBL development, we performed whole-exome sequencing on 41 paired tumor-normal DNA samples from patients with T-LBL. Results We identified 32 putative driver genes using whole-exome sequencing in 41 T-LBL cases, many of which have not previously been described in T-LBL, such as Janus kinase 3 (JAK3), Janus kinase 1 (JAK1), Runt-related transcription factor 1 (RUNX1) and Wilms’ tumor suppressor gene 1 (WT1). When comparing the genetic alterations of T-LBL to T-cell acute lymphoblastic leukemia (T-ALL), we found that JAK-STAT and RAS pathway mutations were predominantly observed in T-LBL (58.5% and 34.1%, respectively), whereas Notch and cell cycle signaling pathways mutations were more prevalent in T-ALL. Notably, besides notch receptor 1 (NOTCH1), mutational status of plant homeodomain (PHD)-like finger protein 6 (PHF6) was identified as another independent factor for good prognosis. Of utmost interest is that co-existence of PHF6 and NOTCH1 mutation status might provide an alternative for early therapeutic stratification in T-LBL. Conclusions Together, our findings will not only provide new insights into the molecular and genetic mechanisms of T-LBL, but also have tangible implications for clinical practice.
目的T细胞淋巴母细胞淋巴瘤(T-LBL)是前体T细胞的侵袭性肿瘤,然而 由于其罕见性,尚未进行大型T-LBL队列。本研究的目的是鉴定T-LBL中假定的驱动基因。方法为了深入了解T-LBL发生的遗传机制,我们对41份来自T-LBL患者的配对肿瘤正常DNA样本进行了全外显子组测序。结果我们在41例T-LBL病例中使用全外显子组测序鉴定了32个假定的驱动基因,其中许多先前未在T-LBL中描述,如Janus激酶3(JAK3)、Janus激酶1(JAK1)、Runt相关转录因子1(RUNX1)和Wilms抑癌基因1(WT1)。当比较T-LBL和T细胞急性淋巴细胞白血病(T-ALL)的基因改变时,我们发现JAK-STAT和RAS通路突变主要在T-LBL中观察到(分别为58.5%和34.1%),而Notch和细胞周期信号通路突变在T-ALL中更普遍。值得注意的是,除了notch受体1(NOTCH1)外,植物同源结构域(PHD)样指状蛋白6(PHF6)的突变状态被确定为预后良好的另一个独立因素。最令人感兴趣的是,PHF6和NOTCH1突变状态的共存可能为T-LBL的早期治疗分层提供一种替代方案。结论总之,我们的研究结果不仅将为T-LBL的分子和遗传机制提供新的见解,而且对临床实践具有实际意义。
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引用次数: 3
Prognostic and incremental value of computed tomography-based radiomics from tumor and nodal regions in esophageal squamous cell carcinoma 基于计算机断层扫描的食管鳞状细胞癌肿瘤和淋巴结区域放射组学的预后和增量价值
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.02
B. Cao, Kun Mi, W. Dai, Tong Liu, T. Xie, Qiang Li, J. Lang, Yongtao Han, Lin Peng, Qifeng Wang
Objective This study aimed to evaluate the prognostic value of preoperative radiomics and establish an integrated model for esophageal squamous cell cancer (ESCC). Methods A total of 931 patients were retrospectively enrolled in this study (training cohort, n=624; validation cohort, n=307). Radiomics features were obtained by contrast-enhanced computed tomography (CT) before esophagectomy. A radiomics index was set based on features of tumor and reginal lymph nodes by using the least absolute shrinkage and selection operator (LASSO) Cox regression. Prognostic nomogram was built based on radiomics index and other independent risk factors. The prognostic value was assessed by using Harrell’s concordance index, time-dependent receiver operating characteristics and Kaplan-Meier curves. Results Twelve radiomic features from tumor and lymph node regions were identified to build a radiomics index, which was significantly associated with overall survival (OS) in both training cohort and validation cohort. The radiomics index was highly correlated with clinical tumor-node-metastasis (cTNM) and pathologic TNM (pTNM) stages, but it demonstrated a better prognostic value compared with cTNM stage and was almost comparable with pTNM stage. Multivariable Cox regression showed that the radiomics index was an independent prognostic factor. An integrated model was constructed based on gender, preoperative serum sodium concentration, pTNM and the radiomics index for clinical usefulness. The integrated model demonstrated discriminatory ability better compared with the traditional clinical-pathologic model and pTNM alone, indicating incremental value for prognosis. Conclusions CT-based radiomics for primary tumor and reginal lymph nodes was sufficient in predicting OS for patients with ESCC. The integrated model demonstrated incremental value for prognosis and was robust for clinical applications.
目的评价术前放射组学对癌症食管鳞状细胞癌(ESCC)预后的价值,建立食管鳞状细胞瘤综合模型。方法共有931名患者被回顾性纳入本研究(训练队列,n=624;验证队列,n=307)。在食管切除术前通过对比增强计算机断层扫描(CT)获得放射组学特征。基于肿瘤和区域淋巴结的特征,使用最小绝对收缩和选择算子(LASSO)Cox回归设置放射组学指数。根据放射组学指数和其他独立的危险因素建立预后列线图。采用Harrell一致性指数、时间依赖性受试者操作特征和Kaplan-Meier曲线评估预后价值。结果确定了来自肿瘤和淋巴结区域的12个放射组学特征,以建立放射组学指数,该指数与训练队列和验证队列的总生存率(OS)显著相关。放射组学指标与临床肿瘤淋巴结转移(cTNM)和病理TNM(pTNM)分期高度相关,但与cTNM分期相比具有更好的预后价值,几乎与pTNM分期相当。多变量Cox回归显示放射组学指数是一个独立的预后因素。基于性别、术前血清钠浓度、pTNM和放射组学指数构建了一个综合模型,用于临床应用。与传统的临床病理模型和单独的pTNM相比,整合模型表现出更好的辨别能力,表明其对预后的价值增加。结论基于CT的原发肿瘤和区域淋巴结放射组学足以预测ESCC患者的OS。该综合模型显示了对预后的增量价值,并且在临床应用中是稳健的。
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引用次数: 3
CSCO guidelines for colorectal cancer version 2022: Updates and discussions CSCO结直肠癌癌症指南2022版:更新和讨论
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.01
Z. Yuan, Shanshan Weng, Chenyang Ye, Hanguang Hu, Suzhan Zhang, Ying Yuan
1Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; 2Department of Medical Oncology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; 3Department of Colorectal Surgery and Oncology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China; 4Cancer Center, Zhejiang University, Hangzhou 310058, China *These authors contributed equally to this work. Correspondence to: Ying Yuan. Department of Medical Oncology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China. Email: yuanying1999@zju.edu.cn; Suzhan Zhang. Department of Colorectal Surgery and Oncology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China. Email: zrsj@zju.edu.cn.
1教育部癌症预防与干预重点实验室放射肿瘤科,浙江大学医学院第二附属医院,杭州310009;2浙江大学医学院第二附属医院肿瘤内科,杭州310009;3浙江大学医学院第二附属医院结直肠癌肿瘤科,杭州310009;4浙江大学癌症中心,杭州310058,中国*这些作者对这项工作做出了同样的贡献。通讯:应元。浙江大学医学院附属第二医院肿瘤内科,杭州310009。电子邮件:yuanying1999@zju.edu.cn;张素湛。浙江大学医学院第二附属医院结直肠癌肿瘤科,杭州310009。电子邮件:zrsj@zju.edu.cn.
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引用次数: 14
Pan-cancer tumor-infiltrating T cells: A great hallmark in cancer immunology research 泛癌肿瘤浸润性T细胞:癌症免疫学研究的重要标志
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.06
Anqiang Wang, Z. Bu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing 100142, China Correspondence to: Zhaode Bu, MD. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing 100142, China. Email: buzhaode@outlook.com.
北京大学肿瘤医院胃肠道肿瘤中心,癌变与转化研究教育部重点实验室,北京100142通讯作者:卜昭德博士。北京大学肿瘤医院胃肠道肿瘤中心,癌变与转化研究教育部重点实验室,北京100142电子邮件:buzhaode@outlook.com。
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引用次数: 0
Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics EpCAM、MUC1、WT1在上皮性卵巢癌中CTC检测优化模型的建立及其与临床特征的相关性
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.04
Tongxia Wang, Yan Gao, Xi Wang, Junrui Tian, Yuan Li, Bo Yu, Cuiyu Huang, Hui Li, H. Liang, D. Irwin, H. Tan, Hongyan Guo
Objective Emerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards. Methods We enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model. Results The sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2% vs. 82.2%, P=0.044), and the detection rate of CTCs was higher than the positive rate of CA125 (74.5% vs. 58.2%, P=0.069) in early-stage patients (stage I and II). The detection rate of CTCs was significantly higher in patients with ascitic volume ≥500 mL, suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy (P<0.05). The detection rate of CTCEpCAM+ and CTCMUC1+ was significantly higher in chemo-resistant patients (26.3% vs. 11.9%; 26.4% vs. 13.4%, P<0.05). The median progression-free survival time for CTCMUC1+ patients trended to be longer than CTCMUC1− patients, and overall survival was shorter in CTCMUC1+ patients (P=0.043). Conclusions Our study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTCEpCAM+ and CTCMUC1+ had predictive value for chemotherapy resistance, and the detection of CTCMUC1+ suggested poor prognosis.
目的新的研究表明循环肿瘤细胞(CTCs)在上皮性卵巢癌的诊断、疾病评估、治疗监测和预后方面具有良好的临床价值。然而,由于检测技术多样,灵敏度和特异性不一,缺乏统一的标准,CTC的临床应用仍然受到限制。方法160例上皮性卵巢癌患者作为实验组,90例卵巢良性肿瘤患者50例,健康女性40例作为对照组。我们利用针对两种上皮细胞表面抗原(EpCAM和MUC1)的免疫磁珠富集ctc,并使用多重逆转录聚合酶链反应(RT-PCR)检测三种标记(EpCAM、MUC1和WT1)进行定量。然后采用二元logistic回归分析,以EpCAM、MUC1和WT1为研究对象,建立优化的CTC检测模型。结果优化模型的灵敏度为79.4%,特异度为92.2%。CTC检测模型的特异性显著高于CA125 (92.2% vs. 82.2%, P=0.044),且早期患者(I期和II期)CTC检出率高于CA125阳性率(74.5% vs. 58.2%, P=0.069),腹水容量≥500 mL、行减胞手术次优、化疗2个疗程后血清CA125水平升高的患者CTC检出率显著高于CA125 (P<0.05)。化疗耐药患者CTCEpCAM+和CTCMUC1+的检出率显著高于化疗耐药患者(26.3% vs. 11.9%;26.4% vs. 13.4%, P<0.05)。CTCMUC1+患者的中位无进展生存期倾向于比CTCMUC1−患者更长,CTCMUC1+患者的总生存期更短(P=0.043)。结论本研究提出了一种优化的ctc检测模型,该模型由EpCAM、MUC1和WT1三种标志物的表达水平组成。与CA125相比,我们的模型特异性高,对早期卵巢癌具有更好的诊断价值。CTCEpCAM+、CTCMUC1+检测对化疗耐药有预测价值,CTCMUC1+检测提示预后较差。
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引用次数: 4
Current status and perspectives of conversion therapy for advanced gastric cancer 进展期胃癌转化治疗的现状及展望
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-04-30 DOI: 10.21147/j.issn.1000-9604.2022.02.05
Heli Yang, K. Ji, J. Ji
The concept and strategy of advanced gastric cancer treatment have gradually undergone profound changes with the in-depth understanding of the biology and heterogeneous characteristics of gastric cancer. Moreover, the development and application of new anticancer drugs, including chemotherapy drugs, molecularly targeted drugs and immunotherapy drugs for advanced gastric cancer are reported. The connotation of conversion therapy refers to the unresectable or borderline resectable tumors for surgical technical and/or oncological reasons, after active and effective chemotherapy and other comprehensive treatment, the primary gastric lesions can be reduced to a lower stage, while the metastatic lesions can be effectively controlled, to achieve R0 resection and improve the long-term survival rate. Current promising research results of conversion therapy are mostly from single-arm phase II clinical studies with small samples or retrospective studies. Conversion therapy still faces many challenges, including limited diagnostic and assessment methods, insufficient evidence of highly effective treatment regimens, difficulty in clarifying surgical indications, etc. Therefore, the integrated conversion therapy for advanced gastric cancer needs to be carried out with the close cooperation of a multidisciplinary team. Prospective, multi-center randomized controlled trial studies should be conducted in the future, and precision medicine such as molecular biology should be combined to provide better anticancer drug regimens and higher-level clinical evidence for conversion therapy of advanced gastric cancer.
随着对癌症生物学和异质性特征的深入理解,晚期癌症治疗的理念和策略逐渐发生了深刻的变化。此外,还报道了晚期癌症化疗药物、分子靶向药物和免疫治疗药物等新型抗癌药物的开发和应用。转化治疗的内涵是指由于手术技术和/或肿瘤学原因,不可切除或边缘可切除的肿瘤,经过积极有效的化疗和其他综合治疗,原发性胃病变可以降到较低阶段,而转移性病变可以得到有效控制,实现R0切除,提高远期生存率。目前有希望的转化治疗研究结果大多来自小样本的单臂II期临床研究或回顾性研究。转化治疗仍然面临许多挑战,包括诊断和评估方法有限、高效治疗方案证据不足、手术指征难以明确等。因此,晚期癌症的综合转化治疗需要在多学科团队的密切合作下进行。未来应开展前瞻性、多中心随机对照试验研究,结合分子生物学等精准医学,为晚期癌症转化治疗提供更好的抗癌药物方案和更高水平的临床证据。
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引用次数: 4
Corrigendum to Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis 肿瘤相关巨噬细胞通过tgf - β2/NF-κB/Kindlin-2轴调控胃癌细胞的侵袭转移
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-02-28 DOI: 10.21147/j.issn.1000-9604.2022.01.07
cjcr
[This corrects the article DOI: 10.21147/j.issn.1000-9604.2020.01.09.].
[这更正了文章DOI: 10.21147/j.issn.1000-9604.2020.01.09.]。
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引用次数: 1
Open surgery in the era of minimally invasive surgery 微创外科时代的开放手术
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-02-28 DOI: 10.21147/j.issn.1000-9604.2022.01.06
Zichen Zhao, J. Gu
The benefits and popularity of minimally invasive surgery are undeniable around the globe. However, open surgery is necessary and learning open surgery skills is still a necessity. Open surgery allows for better exposure to the surgical field and provides tactile sensation to facilitate the stereo visual assessment to precisely remove the lesion. Open surgery is still the key to surgical training, and the skills learned from open surgeries remain crucial for unforeseen circumstances and certain conditions like emergencies, challenge cases, or patients with compromised status.
微创手术的好处和受欢迎程度在全球范围内是不可否认的。然而,开放手术是必要的,学习开放手术技能仍然是必要的。开放式手术可以更好地暴露在手术区域,并提供触感以促进立体视觉评估,从而精确地去除病变。开放式手术仍然是外科培训的关键,从开放式手术中学到的技能对于不可预见的情况和某些情况仍然至关重要,如紧急情况、挑战性病例或状态受损的患者。
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引用次数: 5
Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage I−III colorectal cancer CT图像放射组学分析与肿瘤生态系统多样化的耦合:对I - III期结直肠癌总生存率的新见解
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-02-28 DOI: 10.21147/j.issn.1000-9604.2022.01.04
Yanqi Huang, Lan He, Zhenhui Li, Xin Chen, Chu Han, Ke Zhao, Yuan Zhang, Jin Qu, Y. Mao, C. Liang, Zaiyi Liu
Objective This study aimed to establish a method to predict the overall survival (OS) of patients with stage I−III colorectal cancer (CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification. Methods We retrospectively identified 161 consecutive patients with stage I−III CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction. Results The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio (HR)=6.670; 95% confidence interval (95% CI): 3.433−12.956; P<0.001), external validation cohort 1 (HR=2.866; 95% CI: 1.646−4.990; P<0.001) and external validation cohort 2 (HR=3.342; 95% CI: 1.289−8.663; P=0.002). Incorporating the EcoRad signature into the prediction model presented a higher prediction ability (P<0.001) with respect to the C-index (0.813, 95% CI: 0.804−0.822 in the training cohort; 0.758, 95% CI: 0.751−0.765 in the external validation cohort 1; and 0.746, 95% CI: 0.722−0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis (TNM) system, as well as a better calibration, improved reclassification and superior clinical usefulness. Conclusions This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage I−III CRC patients.
目的本研究旨在通过CT图像的放射组学分析与肿瘤生态系统多样性的测量相结合,建立预测I-III期癌症(CRC)患者总生存期(OS)的方法。方法我们回顾性地确定了161名连续接受根治性切除的I-III期CRC患者作为训练队列。共有248名患者被招募作为外部验证队列1进行临时独立验证,103名来自外部研究所的患者被招募为外部验证队列2。利用肿瘤生态系统多样性的测量,提取CT图像特征来描述肿瘤空间异质性,以构建一种标记物,称为EcoRad特征。使用多变量Cox回归来评估EcoRad特征,构建预测模型以证明其对OS预测的传统分期系统的增量价值。结果在训练队列中,EcoRad特征与OS显著相关[风险比(HR)=6.670;95%置信区间(95%CI):3.433−12.956;P<0.001),外部验证队列1(HR=2.866;95%CI:1.646−4.990;P=0.001)和外部验证队列2(HR=3.342;95%CI:12.89−8.663;P=0.002)将EcoRad特征纳入预测模型,与仅纳入肿瘤、淋巴结、,转移(TNM)系统,以及更好的校准、改进的重新分类和优越的临床实用性。结论本研究通过放射组学分析与肿瘤生态系统多样性测量相结合,建立了一种测量CRC空间异质性的方法,并表明该方法可以有效预测OS,可作为I−III期CRC患者风险分层的补充。
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引用次数: 1
Deregulated expression and subcellular localization of CPSF6, a circRNA-binding protein, promote malignant development of esophageal squamous cell carcinoma circRNA结合蛋白CPSF6的表达下调和亚细胞定位促进食管鳞状细胞癌的恶性发展
IF 5.1 2区 医学 Q1 ONCOLOGY Pub Date : 2022-02-28 DOI: 10.21147/j.issn.1000-9604.2022.01.02
Shichao Guo, Guang-li Wang, Zitong Zhao, Dan Li, Yongmei Song, Q. Zhan
Objective Cleavage and polyadenylation specific factor 6 (CPSF6) has been documented as an oncoprotein in different types of cancer. However, functions of CPSF6 have not been investigated yet in esophageal squamous cell carcinoma (ESCC). Here, we aimed to investigate the potential clinical values and biological functions of CPSF6 in ESCC. Methods For determining the expression level of CPSF6 in ESCC patients, we analyzed published data, performed quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. Kaplan-Meier curves and log-rank tests were used for survival analyses. GO and KEGG analyses were done for CPSF6-related genes. Cell proliferation, colony formation and xenograft assays were conducted to verify the effects of CPSF6 on ESCC. In addition, cell cycle and apoptosis assays were also performed to manifest the functions of CPSF6 and circCPSF6. RNA pulldown and radioimmunoprecipitation (RIP) assays were used for confirming the interaction between circCPSF6 (hsa_circ_0000417) and CPSF6 protein. The regulatory relationship between CPSF6 protein and circCPSF6 was determined by RT-qPCR. Results We found that CPSF6 was upregulated in ESCC tissues and overexpression of cytoplasmic CPSF6 was associated with poor prognosis. GO and KEGG analyses suggested that CPSF6 could mainly affect cell division in ESCC. Further experiments manifested that CPSF6 promoted cell proliferation and colony formationin vitro. Xenograft assay showed that knockdown of CPSF6 significantly decreased tumor growth rate in vivo. Subsequently, we verified that depletion of CPSF6 led to cell cycle arrest and apoptosis. Finally, we validated that CPSF6, as a circRNA-binding protein, interacted with and regulated its circular isoform circCPSF6 (hsa_circ_0000417), of which depletion also resulted in cell cycle arrest and cell apoptosis in ESCC. Conclusions These findings gave us insight that overexpression of cytoplasmic CPSF6 protein is associated with poor prognosis in ESCC and CPSF6 may function as an oncoprotein, at least in part, through regulating circCPSF6 expression.
目的裂解和多聚腺苷酸化特异性因子6(CPSF6)已被证明是不同类型癌症的癌蛋白。然而,CPSF6在食管鳞状细胞癌(ESCC)中的功能尚未得到研究。在此,我们旨在研究CPSF6在ESCC中的潜在临床价值和生物学功能。方法为了测定CPSF6在ESCC患者中的表达水平,我们分析了已发表的数据,进行了定量实时聚合酶链反应(RT-qPCR)和免疫组织化学分析。Kaplan-Meier曲线和对数秩检验用于生存分析。对CPSF6相关基因进行GO和KEGG分析。进行细胞增殖、集落形成和异种移植物测定以验证CPSF6对ESCC的影响。此外,还进行了细胞周期和凋亡测定,以显示CPSF6和circCPSF6的功能。RNA下拉和放射免疫沉淀(RIP)分析用于确认circCPSF6(hsa_cir_0000417)和CPSF6蛋白之间的相互作用。通过RT-qPCR测定CPSF6蛋白与circCPSF6之间的调控关系。结果发现CPSF6在ESCC组织中表达上调,胞质CPSF6过表达与预后不良有关。GO和KEGG分析表明CPSF6主要影响ESCC细胞的分裂。进一步的实验表明,CPSF6在体外能促进细胞增殖和集落形成。异种移植物分析显示,敲低CPSF6可显著降低体内肿瘤生长速率。随后,我们验证了CPSF6的缺失导致细胞周期停滞和凋亡。最后,我们验证了CPSF6作为一种circRNA结合蛋白,与其环状异构体circCPSF6(hsa_cir_0000417)相互作用并调节其,其缺失也导致ESCC中的细胞周期停滞和细胞凋亡。结论细胞质CPSF6蛋白的过度表达与ESCC的预后不良有关,CPSF6可能至少部分通过调节circCPSF6的表达而发挥癌蛋白的作用。
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引用次数: 3
期刊
Chinese Journal of Cancer Research
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