Clinical Research (Excluding Clinical Trials)最新文献

筛选
英文 中文
Abstract LB057: Whole exome sequencing of tumor tissue and circulating tumor DNA ingastrointestinal stromal tumors (GIST) LB057:胃肠道间质瘤(GIST)肿瘤组织和循环肿瘤DNA全外显子组测序
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-LB057
N. Coleman, Charles Abbot, N. Somaiah, S. Piha-Paul, S. Pant, J. Rodón, S. G. Call, S. Boyle, F. Meric-Bernstam, F. Janku
{"title":"Abstract LB057: Whole exome sequencing of tumor tissue and circulating tumor DNA ingastrointestinal stromal tumors (GIST)","authors":"N. Coleman, Charles Abbot, N. Somaiah, S. Piha-Paul, S. Pant, J. Rodón, S. G. Call, S. Boyle, F. Meric-Bernstam, F. Janku","doi":"10.1158/1538-7445.AM2021-LB057","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB057","url":null,"abstract":"Background: The discovery of oncogenic mutations as potential targets for cancer therapy has revolutionized the treatment of GIST and other cancers. However, adaptive resistance ultimately develops in nearly all patients, which emphasizes the need for a more detailed understanding of the underlying molecular profile. Methods: Using the Personalis ImmunoID NeXT Platform® (Personalis, Inc.; Menlo Park, CA), an augmented exome/transcriptome platform and analysis pipeline, we performed whole exome sequencing (WES) and whole transcriptome total RNA sequencing (RNA-Seq) of paired baseline tumor and normal tissue. NeXT Liquid Biopsy™ (Personalis, Inc.) was used for WES of plasma-derived ctDNA from serially collected samples collected at baseline, after 1 month and at progression to experimental systemic therapies in 15 patients with advanced/metastatic GIST. Results: WES of tumor tissue samples from all 15 patients confirmed underlying KIT mutation in all patients. There was large heterogeneity of other molecular alterations, which included therapeutically relevant molecular alterations, such as microsatellite instability-high (MSI-high) in 1 sample. RNA-Seq of tumor tissue revealed recurrent overexpression of GALR2, NY-ESO-1 and other genes involved in cancer progression, angiogenesis and anticancer immunity. Patients with response to systemic therapies demonstrated lower levels of cytolytic activity measured by CYT score in tumor tissue compared to patients without response (P=0.04). KIT mutations were detected in serially collected ctDNA samples from 12 (80%) of 15 patients. Quantity of KIT and other mutant ctDNA dynamically tracked the clonal evolution and clinical course during systemic therapy. Conclusions: Comprehensive genomic profiling (WES and RNA-Seq) of tumor tissue and WES of serially collected ctDNA is feasible and detects underlying druggable KIT mutations and other molecular alterations. Citation Format: Niamh Coleman, Charles Abbot, Neeta Somaiah, Sarina Piha-Paul, Shubham Pant, Jordi Rodon, S. Greg Call, Sean Boyle, Funda Meric-Bernstam, Filip Janku. Whole exome sequencing of tumor tissue and circulating tumor DNA ingastrointestinal stromal tumors (GIST) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB057.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"246 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76982439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 581: Prognostic implication of circulating tumor-derived KRAS mutation in pancreatic ductal adenocarcinoma 581:循环肿瘤来源的KRAS突变在胰腺导管腺癌中的预后意义
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-581
Min-Kyeong Kim, Dongeun Lee, Yun-Hee Kim, Sang Jae Park, S. Woo, S. Kong
{"title":"Abstract 581: Prognostic implication of circulating tumor-derived KRAS mutation in pancreatic ductal adenocarcinoma","authors":"Min-Kyeong Kim, Dongeun Lee, Yun-Hee Kim, Sang Jae Park, S. Woo, S. Kong","doi":"10.1158/1538-7445.AM2021-581","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-581","url":null,"abstract":"Circulating tumor DNA (ctDNA) has been evaluated as potential biomarkers for prognosis in pancreatic adenocarcinoma(PDAC) including our previous study, which proved KRAS mutation as a prognostic marker through the quantitative analysis. Then we investigated in a larger samples to validate the results of previous studies. Total of 213 PDAC patients has been enrolled in this study and the median age was 66 years old and 120 males (56.1%). Plasma was separated by established centrifugation method and ctDNA was extracted from 2.0 mL plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen Cat# 61504, Hilden, Germany) or a Chemagic cfDNA 2K kit (PerkinElmer, Waltham, Massachusetts, U.S.). Extracted ctDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). The detection of KRAS mutation was performed using QX200 Droplet Digital PCR System (Biorad, USA) by KRAS screening multiplex droplet digital PCR kit which covers seven common mutation sites (Biorad, USA) and compared with that in 93 matched formalin-fixed paraffin-embedded (FFPE) tissues. Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). The KRAS mutation rates in tissue and ctDNA were 98.9% and 82.8%, respectively, and the concordance rate between them was 78 of 93 samples (83.9%). Univariable analyses demonstrated that KRAS fraction (Hazard ratio (HR), 1.59; 95% CI, 1.02-2.49; P = 0.040) were significant factors for PFS, whereas KRAS mutation concentration (HR, 1.69; 95% CI, 1.03-2.77; P = 0.038) and KRAS fraction (HR, 1.88; 95% CI, 1.17-3.02; P = 0.010) for OS. This study proved the usefulness of the KRAS mutation of ctDNA as a prognostic marker in PDAC. (This study was supported by National cancer center, Korea, Grant no. 1910192) Citation Format: Min Kyeong Kim, Dong-Eun Lee, Yun Hee Kim, Sang Jae Park, Sang Myung Woo, Sun-Young Kong. Prognostic implication of circulating tumor-derived KRAS mutation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 581.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77058594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract LB062: Efficacy of Responder-derived Fecal Microbiota Transplant (R-FMT) and Pembrolizumab in Anti-PD-1 Refractory Patients with Advanced Melanoma LB062:反应源性粪便微生物群移植(R-FMT)和派姆单抗在抗pd -1难治性晚期黑色素瘤患者中的疗效
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-LB062
D. Davar, A. Dzutsev, J. McCulloch, R. Rodrigues, Joe-Marc Chauvin, Robert M. Morrison, R. DeBlasio, Carmine Menna, Quanquan Ding, Ornella Pagliano, Bochra Zidi, Shuowen Zhang, J. Badger, Marie Vetizou, A. Cole, M. R. Fernandes, Stephanie Prescott, R. G. Costa, A. Balaji, A. Morgun, I. Vujkovic-Cvijin, Hong Wang, Amir A. Borhani, M. Schwartz, Howard M. Dubner, Scarlett J. Ernst, Amy Rose, Y. Najjar, Y. Belkaid, J. Kirkwood, G. Trinchieri, H. Zarour
{"title":"Abstract LB062: Efficacy of Responder-derived Fecal Microbiota Transplant (R-FMT) and Pembrolizumab in Anti-PD-1 Refractory Patients with Advanced Melanoma","authors":"D. Davar, A. Dzutsev, J. McCulloch, R. Rodrigues, Joe-Marc Chauvin, Robert M. Morrison, R. DeBlasio, Carmine Menna, Quanquan Ding, Ornella Pagliano, Bochra Zidi, Shuowen Zhang, J. Badger, Marie Vetizou, A. Cole, M. R. Fernandes, Stephanie Prescott, R. G. Costa, A. Balaji, A. Morgun, I. Vujkovic-Cvijin, Hong Wang, Amir A. Borhani, M. Schwartz, Howard M. Dubner, Scarlett J. Ernst, Amy Rose, Y. Najjar, Y. Belkaid, J. Kirkwood, G. Trinchieri, H. Zarour","doi":"10.1158/1538-7445.AM2021-LB062","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB062","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76416590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Abstract 559: Next-generation sequencing of circulating tumor DNA in advanced lung cancer patients treated with the immune checkpoint inhibitor 559:免疫检查点抑制剂治疗晚期肺癌患者循环肿瘤DNA的新一代测序
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-559
W. Cho, W. Hsiao, K. Tan, J. Li, Shu-Jen Chen
{"title":"Abstract 559: Next-generation sequencing of circulating tumor DNA in advanced lung cancer patients treated with the immune checkpoint inhibitor","authors":"W. Cho, W. Hsiao, K. Tan, J. Li, Shu-Jen Chen","doi":"10.1158/1538-7445.AM2021-559","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-559","url":null,"abstract":"Introduction: Advanced lung cancer is a highly lethal disease worldwide. Recently, immune checkpoint inhibitors (ICIs) have made a significant breakthrough in the management of advanced lung cancer. Even though only a proportion of patients respond to ICI, the duration of such responders due to immunological memory is remarkable and is longer than other agents in refractory disease. Circulating tumor DNA (ctDNA) exhibits the potential in identifying genomic alterations and monitoring ICI treatment in advanced lung cancer patients. Identification of these genomic alterations may help to triage patients who will achieve better clinical benefit with minimal toxicity in therapies with ICIs. Materials and Methods: ctDNA mutational changes were monitored in the longitudinal blood samples (n = 39) of seven stage IV lung adenocarcinoma patients between baseline and after ICI therapy (complete monitoring until disease progression or the end of follow-up). The mutation spectrum in these patients was detected by a next-generation sequencing panel consisting of 50 cancer-related genes. Results: Among the seven patients, 15 variants were identified. All patients harbored at least one mutation, with an average of 2.1 mutations per patient. The most frequently mutated genes were TP53 (42.9%) and EGFR (42.9%). Baseline measurement showed eight mutations (EGFR E746V, L747P, A763_Y764insFQEA; TP53 R158C, A159S; ATM V2439G; ERBB2 Y772_A755dup; KRAS Q61H) in five patients. Seven mutations (TP53 I254fs, I255del, A276P, R280S; EGFR I740_K745dup; FGFR2 G261fs; STK11 D162fs) were observed in four patients following ICI therapy, suggesting that these alterations might be acquired during treatment. Most importantly, all patients harbored at least one clinically targetable gene mutation, including ATM, EGFR, ERBB2, STK11, and KRAS. Among these genes, the oncogenic mutations of EGFR and ERBB2 are FDA-recognized biomarkers predictive of response to specific targeted drugs in non-small cell lung cancer. Conclusion: This study demonstrates that ctDNA monitoring is a useful method for molecular genotyping of advanced lung cancer patients. Genomic profiling of liquid biopsy may help to identify gene signatures for biomarkers predictive of response to treatment. The gene mutations identified in the individual patient of this study may help access the clinical benefit of therapy with ICIs or other drugs. The identification of druggable genes may potentially help to develop more effective treatment strategies. Considering the small percentage of patients receiving ICI therapy, this is a small-scale pilot study and a larger study is warranted. Citation Format: William C. Cho, Wen Hsiao, Kien Thiam Tan, Jacky Y. Li, Shu-Jen Chen. Next-generation sequencing of circulating tumor DNA in advanced lung cancer patients treated with the immune checkpoint inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. P","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"151 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76460343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 558: Muti-gene ARMS PCR using both cfDNA and cfRNAin the supernatant of pleural effusion achieves rapid and accuracy driver gene mutations detection 558:利用胸膜积液上清cfDNA和cfRNAin进行多基因ARMS PCR,实现了快速、准确的驱动基因突变检测
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-558
Xuejing Chen, Kun Li, Zichen Liu, F. Gai, G. Zhu, Shun Lu, N. Che
{"title":"Abstract 558: Muti-gene ARMS PCR using both cfDNA and cfRNAin the supernatant of pleural effusion achieves rapid and accuracy driver gene mutations detection","authors":"Xuejing Chen, Kun Li, Zichen Liu, F. Gai, G. Zhu, Shun Lu, N. Che","doi":"10.1158/1538-7445.AM2021-558","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-558","url":null,"abstract":"Background Pleural effusion from patients with advanced non-small cell lung cancer has been proved valuable for molecular analysis, especially when the tissue sample not available. However, simultaneous detection of multiple driver gene alterations especially the fusions is still challenging. Methods In this study, 77 patients with advanced NSCLC and pleural effusion were enrolled, 49 of whom had matched tumor tissues. Supernatants, cell sediments, and FFPE cell blocks were prepared from pleural effusion samples for detection of driver alterations by a PCR-based 9-gene mutation detection kit. Results In addition to mutations in EGFR, KRAS and HER2 detected in genomic DNA from cell sediments, FFPE cell blocks, and in cfDNA from supernatants, and fusions in ALK detected in RNA from cell sediments and FFPE cell blocks, fusions in ALK were also successfully detected in cfRNA from supernatants. Compared with matched tumor tissue, the supernatant showed the highest overall sensitivity (81.3%), with 81.5% for SNV/Indels by cfDNA and 80% for fusions by cfRNA, followed by FFPE cell blocks (71.0%) and the cell sediments (66.7%). Within the group of treatment-naive patients or malignant cells observed in the cell sediments, supernatant showed higher overall sensitivity (89.5%, 92.3%) with both 100% for fusions. Based on the results, an optimized driver gene mutations detection procedure of pleural effusion is proposed. With the proposed procedure, an overall sensitivity 85.3% was achieved, with 82.1% for SNV/Indels and 100% for fusions. Conclusions CfDNA and cfRNA derived from pleural effusion supernatant (PES) have been successfully tested with a PCR-based multi-gene detection kit. An optimized procedure could maximize clinical value of testing pleural effusion samples and has good potential for routine clinical application. Citation Format: Xuejing Chen, Kun Li, Zichen Liu, Fei Gai, Guanshan Zhu, Shun Lu, Nanying Che. Muti-gene ARMS PCR using both cfDNA and cfRNAin the supernatant of pleural effusion achieves rapid and accuracy driver gene mutations detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 558.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76754187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract LB030: A novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 LB030:一种靶向CD19近端膜结构域的新型抗CD19嵌合抗原受体T细胞产物
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-LB030
Ki Hyun Kim, R. Patel, Yong Gu Lee, Soohwan Kim, Jihoon Choi, Sung-min Kim, G. Kim, Jong-Ho Lee, Hyun-Jong Lee, Ji-Ho Park, Guewha Lee, Lei Cui, M. Yoon, Ki-Hyun Kim, Soohyun Kim, I. Hwang, Youngha Lee, Bong-Kook Ko, Jong-Seo Lee, J. Chung, M. Ruella
{"title":"Abstract LB030: A novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19","authors":"Ki Hyun Kim, R. Patel, Yong Gu Lee, Soohwan Kim, Jihoon Choi, Sung-min Kim, G. Kim, Jong-Ho Lee, Hyun-Jong Lee, Ji-Ho Park, Guewha Lee, Lei Cui, M. Yoon, Ki-Hyun Kim, Soohyun Kim, I. Hwang, Youngha Lee, Bong-Kook Ko, Jong-Seo Lee, J. Chung, M. Ruella","doi":"10.1158/1538-7445.AM2021-LB030","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB030","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76833181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 589: CCR5 upregulation in two subtypes of tumor associated circulating cells predict worse prognosis in metastatic breast cancer 589:两种肿瘤相关循环细胞亚型的CCR5上调预示转移性乳腺癌预后较差
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-589
A. Raghavakaimal, M. Cristofanilli, Cha-Mei Tang, R. Alpaugh, Kirby P. Gardener, S. Chumsri, D. Adams
{"title":"Abstract 589: CCR5 upregulation in two subtypes of tumor associated circulating cells predict worse prognosis in metastatic breast cancer","authors":"A. Raghavakaimal, M. Cristofanilli, Cha-Mei Tang, R. Alpaugh, Kirby P. Gardener, S. Chumsri, D. Adams","doi":"10.1158/1538-7445.AM2021-589","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-589","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74415468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 351: Serum ST6GAL1 is a novel biomarker for predicting efficacy of tyrosine kinase inhibitors in hepatocellular carcinoma by detecting FGF19 expressing tumor 摘要:血清ST6GAL1是一种新的生物标志物,可通过检测表达FGF19的肿瘤来预测酪氨酸激酶抑制剂在肝癌中的疗效
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-351
Yuta Myojin, T. Kodama, H. Hikita, R. Sakamori, T. Takehara
{"title":"Abstract 351: Serum ST6GAL1 is a novel biomarker for predicting efficacy of tyrosine kinase inhibitors in hepatocellular carcinoma by detecting FGF19 expressing tumor","authors":"Yuta Myojin, T. Kodama, H. Hikita, R. Sakamori, T. Takehara","doi":"10.1158/1538-7445.AM2021-351","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-351","url":null,"abstract":"Background: Several tyrosine kinase inhibitors (TKIs) have been developed for hepatocellular carcinoma (HCC). However, their efficacy is limited partly due to the diversity of its genetic drivers. In this study, we sought for HCC oncogenes involved in susceptibility of TKIs and aimed to develop their serum biomarkers. Methods: We created a novel HCC mouse model in which tumor diversity of genetic drivers was recapitulated by transposon-based intrahepatic delivery of a pooled barcode-tagged 10-oncogene cDNA library. Tumor-bearing mice were then treated with lenvatinib (LEN), or sorafenib (SOR), or vehicle until moribund. The relative abundance of each oncogene cDNA in each tumor was quantified by a high-throughput barcode sequence. In vitro LEN susceptibility was assessed in 9 human HCC cell lines and LEN-resistant Hep3B cells (LEN-R) established by its long-term exposure. Tumor-derived secreted proteins were screened via cellular proteomic and secretomic analyses of Huh7 and Hep3B cells. Serum and tumor levels of identified proteins were examined in 62 HCC patients who underwent hepatectomy. Efficacy of biomarker candidates was assessed using pre-treated serum of 96 HCC patients who underwent TKI therapy. Results: Mice developed multiple genetically heterogeneous liver tumors as early as 2 weeks after delivery of the pooled library. Upon TKI administration, their sequencing analysis showed that LEN selectively eliminated FGF19-expressing tumors, whereas SOR did MET- and NRAS-expressing tumors. Among 9 HCC cell lines, HuH7 and Hep3B cells showed the highest FGF19 levels and LEN susceptibility. FGF19 inhibition eliminated their susceptibility. LEN-R cells showed reduction of FGF19 levels and got resensitized to LEN by FGF19 replenishment. Thus, FGF19-driven HCC is susceptible to LEN. Proteomics identified 6 secreted proteins downregulated by FGF19 inhibition in Hep3B cells. Among them, ST6GAL1 was the most positively correlated with FGF19 in HCC cell lines and in mouse and human HCC tissues. FGF19 knockdown in Hep3B cells decreased phosphorylation of STAT3, whereas FGF19 overexpression increased its phosphorylation with ST6GAL1 upreguation. Silencing of STAT3 signal by inhibitor or siRNA significantly decreased ST6GAL1 expression. In surgically-resected HCC patients, serum ST6GAL1 levels were positively correlated with tumor site FGF19 expression and were markers for disease progression. In TKI-treated HCC patients with high baseline serum ST6GAL1 levels, LEN therapy showed significantly longer survival than SOR. Conclusion: ST6GAL1 is a tumor-derived secreted protein downstream of FGF19 and may be a useful serum biomarker for identification of patients with FGF19-driven HCC who may benefit from LEN therapy. Citation Format: Yuta Myojin, Takahiro Kodama, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara. Serum ST6GAL1 is a novel biomarker for predicting efficacy of tyrosine kinase inhibitors in hepatocellular carcinoma by detecting FGF19 expressing ","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76223727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 331: Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc) 外周血neoepitope (neoE)特异性T细胞的鉴定用于乳腺癌(bc)或卵巢癌(oc)患者的过继性neocr -T细胞治疗
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-331
M. Cristea, B. Chmielowski, D. Oh, R. Funke, D. Bota, M. Abedi
{"title":"Abstract 331: Characterization of neoepitope (neoE)-specific T cells from peripheral blood for adoptive neoTCR-T cell therapy for patients with breast cancer (bc) or ovarian cancer (oc)","authors":"M. Cristea, B. Chmielowski, D. Oh, R. Funke, D. Bota, M. Abedi","doi":"10.1158/1538-7445.AM2021-331","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-331","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76274263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract 651: A novel gene signature that predicts recurrence following hepatectomy in patients with colorectal liver metastasis 651:一种新的基因标记可预测结直肠肝转移患者肝切除术后复发
Clinical Research (Excluding Clinical Trials) Pub Date : 2021-07-01 DOI: 10.1158/1538-7445.AM2021-651
Y. Wada, M. Shimada, A. Goel
{"title":"Abstract 651: A novel gene signature that predicts recurrence following hepatectomy in patients with colorectal liver metastasis","authors":"Y. Wada, M. Shimada, A. Goel","doi":"10.1158/1538-7445.AM2021-651","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-651","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"125 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76426155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信