Pub Date : 2022-04-30DOI: 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.
{"title":"Genomic landscape of T-cell lymphoblastic lymphoma","authors":"Zhaoming Li, Yue Song, Mingzhi Zhang, Yiming Wei, Hang Ruan","doi":"10.21147/j.issn.1000-9604.2022.02.03","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.03","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46678770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-30DOI: 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.
{"title":"CSCO guidelines for colorectal cancer version 2022: Updates and discussions","authors":"Z. Yuan, Shanshan Weng, Chenyang Ye, Hanguang Hu, Suzhan Zhang, Ying Yuan","doi":"10.21147/j.issn.1000-9604.2022.02.01","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.01","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45132550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-30DOI: 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.
{"title":"Pan-cancer tumor-infiltrating T cells: A great hallmark in cancer immunology research","authors":"Anqiang Wang, Z. Bu","doi":"10.21147/j.issn.1000-9604.2022.02.06","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.06","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43415986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-30DOI: 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。
{"title":"Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics","authors":"Tongxia Wang, Yan Gao, Xi Wang, Junrui Tian, Yuan Li, Bo Yu, Cuiyu Huang, Hui Li, H. Liang, D. Irwin, H. Tan, Hongyan Guo","doi":"10.21147/j.issn.1000-9604.2022.02.04","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.04","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67629953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-30DOI: 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.
{"title":"Current status and perspectives of conversion therapy for advanced gastric cancer","authors":"Heli Yang, K. Ji, J. Ji","doi":"10.21147/j.issn.1000-9604.2022.02.05","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.02.05","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47516654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis","authors":"cjcr","doi":"10.21147/j.issn.1000-9604.2022.01.07","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.07","url":null,"abstract":"[This corrects the article DOI: 10.21147/j.issn.1000-9604.2020.01.09.].","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42289670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 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.
{"title":"Open surgery in the era of minimally invasive surgery","authors":"Zichen Zhao, J. Gu","doi":"10.21147/j.issn.1000-9604.2022.01.06","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.06","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46996801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 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.
{"title":"Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage I−III colorectal cancer","authors":"Yanqi Huang, Lan He, Zhenhui Li, Xin Chen, Chu Han, Ke Zhao, Yuan Zhang, Jin Qu, Y. Mao, C. Liang, Zaiyi Liu","doi":"10.21147/j.issn.1000-9604.2022.01.04","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.04","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42035376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Deregulated expression and subcellular localization of CPSF6, a circRNA-binding protein, promote malignant development of esophageal squamous cell carcinoma","authors":"Shichao Guo, Guang-li Wang, Zitong Zhao, Dan Li, Yongmei Song, Q. Zhan","doi":"10.21147/j.issn.1000-9604.2022.01.02","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.02","url":null,"abstract":"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.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49348836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-28DOI: 10.21147/j.issn.1000-9604.2022.01.01
Dong-dong Ti, Xin Yan, Jianshu Wei, Zhiqiang Wu, Yao Wang, W. Han
Immunotherapy has revolutionized cancer treatment and substantially improved patient outcomes with respect to multiple types of tumors. However, most patients cannot benefit from such therapies, mainly due to the intrinsic low immunogenicity of cancer cells (CCs) that allows them to escape recognition by immune cells of the body. Immunogenic cell death (ICD), which is a form of regulated cell death, engages in a complex dialogue between dying CCs and immune cells in the tumor microenvironment (TME), ultimately evoking the damage-associated molecular pattern (DAMP) signals to activate tumor-specific immunity. The ICD inducers mediate the death of CCs and improve both antigenicity and adjuvanticity. At the same time, they reprogram TME with a “cold-warm-hot” immune status, ultimately amplifying and sustaining dendritic cell- and T cell-dependent innate sensing as well as the antitumor immune responses. In this review, we discuss how to stimulate ICD based upon the biological properties of CCs that have evolved under diverse stress conditions. Additionally, we highlight how this dynamic interaction contributes to priming tumor immunogenicity, thereby boosting anticancer immune responses. We believe that a deep understanding of these ICD processes will provide a framework for evaluating its vital role in cancer immunotherapy.
{"title":"Inducing immunogenic cell death in immuno-oncological therapies","authors":"Dong-dong Ti, Xin Yan, Jianshu Wei, Zhiqiang Wu, Yao Wang, W. Han","doi":"10.21147/j.issn.1000-9604.2022.01.01","DOIUrl":"https://doi.org/10.21147/j.issn.1000-9604.2022.01.01","url":null,"abstract":"Immunotherapy has revolutionized cancer treatment and substantially improved patient outcomes with respect to multiple types of tumors. However, most patients cannot benefit from such therapies, mainly due to the intrinsic low immunogenicity of cancer cells (CCs) that allows them to escape recognition by immune cells of the body. Immunogenic cell death (ICD), which is a form of regulated cell death, engages in a complex dialogue between dying CCs and immune cells in the tumor microenvironment (TME), ultimately evoking the damage-associated molecular pattern (DAMP) signals to activate tumor-specific immunity. The ICD inducers mediate the death of CCs and improve both antigenicity and adjuvanticity. At the same time, they reprogram TME with a “cold-warm-hot” immune status, ultimately amplifying and sustaining dendritic cell- and T cell-dependent innate sensing as well as the antitumor immune responses. In this review, we discuss how to stimulate ICD based upon the biological properties of CCs that have evolved under diverse stress conditions. Additionally, we highlight how this dynamic interaction contributes to priming tumor immunogenicity, thereby boosting anticancer immune responses. We believe that a deep understanding of these ICD processes will provide a framework for evaluating its vital role in cancer immunotherapy.","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42578044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：