Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-452
W. Bae, J. Hwang, W. K. Hur, M. Nam, Y. Choi, L. Kim, Yeun Ho Lee, William Cheng, Eugene Kim, E. Yu, C. Jung, Jeff Chuang, Victor G. Wang, Y. Chae
TP53-mutation is a poor prognostic marker for uterine corpus endometrial carcinoma (UCEC). TGF-β is known to promote tumor progression via immune suppression, particularly NK and T cell-mediated cytotoxicity, in the tumor microenvironment. We aimed to analyze the impact of TGF-β signaling pathway-related gene mutation on the immune landscape and survival outcomes in TP53-mutated UCEC patients. cBioPortal was queried to obtain the UCEC The Cancer Genome Atlas cohort data (TCGA, 529 patients). The neoantigen counts were predicted using the CloudNeo pipeline. Survival outcomes were compared in the TGF-β signaling pathway-related gene mutated group, which were defined as genetic variances in TGFBR1, TGFBR2, ACVR2A, ACVR1B, SMAD2, SMAD3, or SMAD4, and the TGF-β signaling pathway-related gene non-mutated group. The cytolytic activity score was defined as a geometric mean of mRNA expression of perforin and granzyme. The duration of overall survival and disease-free survival were also obtained from cBioPortal. Out of the 529 UCEC patients, 192(36.3%) cancer tissues with TP53 mutations were analyzed for this study. 44 patients (22.9%) had more than one mutation in their TGF-β signaling pathway-related genes. TGF-β signaling pathway-related gene mutated group, when compared to a non-mutated group, was associated with significantly increased neoantigen counts (519.3 vs. 20.34 ; p Citation Format: William H. Bae, Jin Young Hwang, Won Kyung Hur, Myungwoo Nam, Yoonhee Choi, Leeseul Kim, Yeun Ho Lee, William Cheng, Eugene Kim, Emma Yu, Chan Mi Jung, Jeff Chuang, Victor Wang, Young Kwang Chae. TGF-β signaling pathway-related gene mutations are associated with increased neoantigen counts, enhanced cytolytic activity, and improved survival outcomes in TP53-mutated endometrial carcinoma [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 452.
tp53突变是子宫肌体子宫内膜癌(UCEC)预后不良的标志。已知TGF-β在肿瘤微环境中通过免疫抑制，特别是NK和T细胞介导的细胞毒性，促进肿瘤进展。我们旨在分析TGF-β信号通路相关基因突变对tp53突变UCEC患者免疫景观和生存结局的影响。向cbiopportal查询以获得UCEC the Cancer Genome Atlas队列数据(TCGA, 529例患者)。使用CloudNeo管道预测新抗原计数。比较TGF-β信号通路相关基因突变组(定义为TGFBR1、TGFBR2、ACVR2A、ACVR1B、SMAD2、SMAD3或SMAD4的遗传变异)与TGF-β信号通路相关基因非突变组的生存结果。细胞溶解活性评分定义为穿孔素和颗粒酶mRNA表达的几何平均值。总生存期和无病生存期也从cbiopportal获得。在529例UCEC患者中，本研究分析了192例(36.3%)TP53突变的癌组织。44例(22.9%)患者的TGF-β信号通路相关基因有一个以上突变。TGF-β信号通路相关基因突变组与非突变组相比，新抗原计数显著增加(519.3比20.34;p引文格式:William H. Bae, Jin Young Hwang, Won Kyung Hur, Myungwoo Nam, Yoonhee Choi, Leeseul Kim, Yeun Ho Lee, William Cheng, Eugene Kim, Emma Yu, Chan Mi Jung, Jeff Chuang, Victor Wang, Young Kwang chai。TGF-β信号通路相关基因突变与tp53突变的子宫内膜癌中新抗原计数增加、细胞溶解活性增强和生存结果改善相关[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):452。
{"title":"Abstract 452: TGF-β signaling pathway-related gene mutations are associated with increased neoantigen counts, enhanced cytolytic activity, and improved survival outcomes in TP53-mutated endometrial carcinoma","authors":"W. Bae, J. Hwang, W. K. Hur, M. Nam, Y. Choi, L. Kim, Yeun Ho Lee, William Cheng, Eugene Kim, E. Yu, C. Jung, Jeff Chuang, Victor G. Wang, Y. Chae","doi":"10.1158/1538-7445.AM2021-452","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-452","url":null,"abstract":"TP53-mutation is a poor prognostic marker for uterine corpus endometrial carcinoma (UCEC). TGF-β is known to promote tumor progression via immune suppression, particularly NK and T cell-mediated cytotoxicity, in the tumor microenvironment. We aimed to analyze the impact of TGF-β signaling pathway-related gene mutation on the immune landscape and survival outcomes in TP53-mutated UCEC patients. cBioPortal was queried to obtain the UCEC The Cancer Genome Atlas cohort data (TCGA, 529 patients). The neoantigen counts were predicted using the CloudNeo pipeline. Survival outcomes were compared in the TGF-β signaling pathway-related gene mutated group, which were defined as genetic variances in TGFBR1, TGFBR2, ACVR2A, ACVR1B, SMAD2, SMAD3, or SMAD4, and the TGF-β signaling pathway-related gene non-mutated group. The cytolytic activity score was defined as a geometric mean of mRNA expression of perforin and granzyme. The duration of overall survival and disease-free survival were also obtained from cBioPortal. Out of the 529 UCEC patients, 192(36.3%) cancer tissues with TP53 mutations were analyzed for this study. 44 patients (22.9%) had more than one mutation in their TGF-β signaling pathway-related genes. TGF-β signaling pathway-related gene mutated group, when compared to a non-mutated group, was associated with significantly increased neoantigen counts (519.3 vs. 20.34 ; p Citation Format: William H. Bae, Jin Young Hwang, Won Kyung Hur, Myungwoo Nam, Yoonhee Choi, Leeseul Kim, Yeun Ho Lee, William Cheng, Eugene Kim, Emma Yu, Chan Mi Jung, Jeff Chuang, Victor Wang, Young Kwang Chae. TGF-β signaling pathway-related gene mutations are associated with increased neoantigen counts, enhanced cytolytic activity, and improved survival outcomes in TP53-mutated endometrial carcinoma [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 452.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79481128","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-435
R. Gianani, Will Paces, Elliott Ergon, V. Adisetiyo, C. Caldwell
{"title":"Abstract 435: A novel image analysis assay for determining programmed death-ligand 1 (22C3) in non-small cell lung cancer that accounts for tissue and alveolar macrophages","authors":"R. Gianani, Will Paces, Elliott Ergon, V. Adisetiyo, C. Caldwell","doi":"10.1158/1538-7445.AM2021-435","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-435","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84128513","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.am2021-506
P. Stecha, D. Garvin, Julia K. Gilden, Jun Wang, Jamison J. Grailer, Jim Hartnett, G. Krishnan, F. Fan, M. Cong, Z. Cheng
{"title":"Abstract 506: A homogenous PBMC ADCC bioassay enables bridging studies with ADCC reporter bioassays in immunotherapy monoclonal antibody development","authors":"P. Stecha, D. Garvin, Julia K. Gilden, Jun Wang, Jamison J. Grailer, Jim Hartnett, G. Krishnan, F. Fan, M. Cong, Z. Cheng","doi":"10.1158/1538-7445.am2021-506","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-506","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81804017","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-384
Bingnan Zhang, C. Stewart, Qi Wang, R. Cardnell, J. Fujimoto, L. Fernandez, A. Jendrisak, Cole Gilbertson, J. Schonhoft, Joshua T. Jones, A. Anderson, I. Wistuba, Jing Wang, R. Wenstrup, L. Byers
Small cell lung cancer (SCLC) is an aggressive form of neuroendocrine carcinoma, notable for early metastases and rapid relapse despite initial response to frontline platinum-based chemotherapy. To date, there are no validated predictive biomarkers in SCLC, hence all patients are treated the same way. Preclinical studies identified SLFN11, a putative DNA/RNA helicase that blocks replication at stressed replication fork, as a predictive biomarker to a wide range of agents targeting DNA damage such as platinum, topoisomerase I/II inhibitors and PARP inhibitors. Based on these observations, pre-specified biomarker analyses in a clinical trial demonstrated SLFN11 predicts better clinical outcomes in SCLC patients when treated with PARP inhibitor combinations such as temozolomide and veliparib. To better characterize the prevalence, heterogeneity and predictive value of SLFN11 in SCLC, we developed and validated a SLFN11 immunohistochemistry (IHC) assay meeting Clinical Laboratory Improvements Amendments (CLIA) standards, and a novel circulating tumor cell (CTC) assay (Epic Sciences®) to detect the expression level of SLFN11 in SCLC tumors or CTCs and correlated with clinical outcomes. We found that SLFN11 was expressed by IHC in roughly 50% of the SCLC clinical tumor samples, from three separate clinical trial cohorts (total of 207 extensive-stage SCLC patient samples). There was a wide range of H-scores by IHC which suggests heterogeneity in SLFN11 expression (H-score range 1.5-235). Similarly, analyses of patient CTCs from blood samples confirmed that SLFN11 is expressed in about 50% of treatment-naive patients, however SLFN11 expression decreased significantly in patients on platinum treatment and at the time of relapse. Most patients had CTCs with pathologic features consistent with SCLC (i.e., were small, round, had high nuclear-to-cytoplasm ratios, and had salt-and-pepper like chromatin textures), although inter- and intra- patient heterogeneity was observed and SLFN11 expression was observed independent of morphologic subtype. Interestingly, SLFN11 expression was also found in white blood cells in the blood samples and was highest in platinum-naive patients and lowest in patients while on platinum. Together, these data highlight the potential of SLFN11 as a predictive biomarker in SCLC. Based on our group and others9 previous work, SLFN11 positivity by IHC is being used for selection of patients in an ongoing clinical trial (NCT04334941). In addition, given the substantial challenge of obtaining adequate tumor tissue in SCLC either at initial diagnosis or with re-biopsies, blood-based CTC analyses are an important tool to detect SLFN11 expression. Because of the dynamic nature of SLFN11 expression, CTC analyses can be especially valuable for longitudinal monitoring and may have real-time implications for treatment choice and response. Citation Format: Bingnan Zhang, C. Allison Stewart, Carl M. Gay, Qi Wang, Robert Cardnell, Junya Fujimoto, Lui
小细胞肺癌(SCLC)是一种侵袭性神经内分泌癌，尽管最初对一线铂类化疗有反应，但仍以早期转移和快速复发著称。到目前为止，还没有有效的预测SCLC的生物标志物，因此所有患者的治疗方法都是一样的。临床前研究发现，SLFN11是一种假定的DNA/RNA解旋酶，可阻断应激复制叉的复制，作为一种预测性生物标志物，可用于多种靶向DNA损伤的药物，如铂、拓扑异构酶I/II抑制剂和PARP抑制剂。基于这些观察结果，在一项临床试验中预先指定的生物标志物分析表明，SLFN11可以预测SCLC患者在使用PARP抑制剂如替莫唑胺和veliparib联合治疗时更好的临床结果。为了更好地表征SLFN11在SCLC中的患病率、异质性和预测价值，我们开发并验证了一种符合临床实验室改进修正案(CLIA)标准的SLFN11免疫组织化学(IHC)检测方法，以及一种新的循环肿瘤细胞(CTC)检测方法(Epic Sciences®)，以检测SLFN11在SCLC肿瘤或CTC中的表达水平，并与临床结果相关。我们发现在大约50%的SCLC临床肿瘤样本中，免疫组化表达了SLFN11，这些样本来自三个独立的临床试验队列(总共207例大分期SCLC患者样本)。IHC的h值范围很广，表明SLFN11的表达具有异质性(h值范围为1.5-235)。同样，对患者血液样本ctc的分析证实，SLFN11在约50%的未接受治疗的患者中表达，但在接受铂治疗的患者和复发时，SLFN11的表达显著下降。大多数患者的ctc具有与SCLC一致的病理特征(即小，圆，核与细胞质比高，具有盐和胡椒样染色质质地)，尽管观察到患者间和患者体内的异质性，并且观察到SLFN11的表达与形态学亚型无关。有趣的是，血液样本中的白细胞中也发现了SLFN11的表达，并且在铂初用药患者中表达最高，而在铂治疗患者中表达最低。总之，这些数据突出了SLFN11作为SCLC预测生物标志物的潜力。根据我们小组和其他人之前的工作，在一项正在进行的临床试验(NCT04334941)中，IHC的SLFN11阳性被用于选择患者。此外，考虑到在SCLC的初始诊断或再活检中获得足够的肿瘤组织的巨大挑战，基于血液的CTC分析是检测SLFN11表达的重要工具。由于SLFN11表达的动态特性，CTC分析对于纵向监测尤其有价值，并且可能对治疗选择和反应具有实时意义。引用格式:张bingnan, C. Allison Stewart, Carl M. Gay, Wang Qi, Robert Cardnell, Junya Fujimoto, Luisa Fernandez, Adam Jendrisak, Cole Gilbertson, Joseph Schonhoft, Joshua Jones, Amanda K. Anderson, Ignacio I. Wistuba, Jing Wang, Rick Wenstrup, Lauren A. Byers。检测肿瘤组织和循环肿瘤细胞中的DNA复制阻断剂SLFN11预测小细胞肺癌的铂反应[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要nr 384。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-346
Y. Wettergren, E. Odin, G. Carlsson, Pushpa Saksena, A. Edsjö, A. Cara, R. Tell, B. Gustavsson
Background - 5-fluorouracil (5-FU) in combination with the folate leucovorin (LV) has formed the backbone of chemotherapy for advanced colorectal cancer for several decades. A number of genes encode proteins that participate in transportation of LV into the cells, as well as in subsequent metabolic action. We previously reported that high tumoral expression of genes involved in folate transport, polyglutamation, and metabolism was associated with decreased risk of recurrent disease in patients with stage III colorectal cancer treated with 5-FU + LV (FLV) alone, or in combination with oxaliplatin (FLOX) according to the Nordic bolus regimen. The aim of the present study was to determine the association between expression of the folate-associated genes ABCC3, MTHFD2, SLC19A1, SLC25A32, SLC46A1, and TYMS and outcome of patients with metastatic colorectal cancer subjected to palliative chemotherapy. Patients and Methods - A total of 290 patients treated with FLV (n = 113), FLOX (n = 102) or FLV + irinotecan (FLIRI, n = 75) were included. Relative gene expression (ΔCt) was determined in primary tumors by quantitative PCR and analyzed in relation to clinical benefit, based on RECIST criteria and 3-year progression-free survival (PFS). Analyses were conducted on the whole study group, and on subgroups based on tumor stage at primary surgery (subgroup 1, stage I-III; subgroup 2, stage IV). An ANOVA test was used to assess the relationship between expression and clinical benefit. A multivariate Cox proportional hazard model was applied to assess potential associations between genetic markers, clinical variables and PFS. A Stepwise model selection was used to identify a minimal set of variables associated with PFS. Results - Low expression of TYMS and MTHFD2, and high expression of ABCC3 was significantly associated with a clinical benefit in the whole group (p Conclusion - Expression of TYMS, the target enzyme of 5-FU, was strongly associated with clinical benefit in the whole group, whereas expression of TYMS and the folate transporters SLC25A32, and ABCC3 was associated with PFS in the subgroups (stage I-III and stage IV), respectively. The prospective global phase III study AGENT is presently conducted on patients with advanced colorectal cancer, to determine whether expression of these genes can predict response to 5-FU-based chemotherapy that includes LV or the novel folate arfolitixorin. Citation Format: Yvonne Wettergren, Elisabeth Odin, Goran Carlsson, Pushpa Saksena, Anders Edsjo, Alessandro Di Cara, Roger Tell, Bengt Gustavsson. Tumoral expression of folate-associated genes is associated with progression-free survival of patients with advanced colorectal cancer [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 346.
背景- 5-氟尿嘧啶(5-FU)联合叶酸亚叶酸钙(LV)已经形成了几十年来晚期结直肠癌化疗的支柱。许多基因编码的蛋白质参与LV进入细胞的运输，以及随后的代谢作用。我们之前报道过，在北欧单药方案中，5-FU + LV (FLV)单独治疗或与奥沙利铂(FLOX)联合治疗的III期结直肠癌患者中，参与叶酸转运、多谷氨酸化和代谢的高肿瘤基因表达与疾病复发风险降低相关。本研究的目的是确定叶酸相关基因ABCC3、MTHFD2、SLC19A1、SLC25A32、SLC46A1和TYMS的表达与转移性结直肠癌患者姑息性化疗的预后之间的关系。患者和方法:共纳入290例接受FLV (n = 113)、FLOX (n = 102)或FLV +伊立替康(FLIRI, n = 75)治疗的患者。基于RECIST标准和3年无进展生存期(PFS)，通过定量PCR检测原发肿瘤中的相对基因表达(ΔCt)，并分析其与临床获益的关系。对整个研究组进行分析，并根据原发性手术时肿瘤分期进行亚组分析(亚组1,I-III期;亚组2,IV期)。采用方差分析检验评估表达与临床获益之间的关系。应用多变量Cox比例风险模型评估遗传标记、临床变量与PFS之间的潜在关联。采用逐步模型选择来确定与PFS相关的最小变量集。结果-在整个组中，TYMS和MTHFD2的低表达以及ABCC3的高表达与临床获益显著相关(p结论-在整个组中，5-FU的靶酶TYMS的表达与临床获益密切相关，而TYMS和叶酸转运体SLC25A32以及ABCC3的表达分别与亚组(I-III期和IV期)的PFS相关。全球前瞻性III期研究AGENT目前正在晚期结直肠癌患者中进行，以确定这些基因的表达是否可以预测对包括LV或新型叶酸arfolitixorin在内的5- fu化疗的反应。引文格式:Yvonne Wettergren, Elisabeth Odin, Goran Carlsson, Pushpa Saksena, Anders Edsjo, Alessandro Di Cara, Roger Tell, Bengt Gustavsson。肿瘤中叶酸相关基因的表达与晚期结直肠癌患者的无进展生存期相关[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要nr 346。
{"title":"Abstract 346: Tumoral expression of folate-associated genes is associated with progression-free survival of patients with advanced colorectal cancer","authors":"Y. Wettergren, E. Odin, G. Carlsson, Pushpa Saksena, A. Edsjö, A. Cara, R. Tell, B. Gustavsson","doi":"10.1158/1538-7445.AM2021-346","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-346","url":null,"abstract":"Background - 5-fluorouracil (5-FU) in combination with the folate leucovorin (LV) has formed the backbone of chemotherapy for advanced colorectal cancer for several decades. A number of genes encode proteins that participate in transportation of LV into the cells, as well as in subsequent metabolic action. We previously reported that high tumoral expression of genes involved in folate transport, polyglutamation, and metabolism was associated with decreased risk of recurrent disease in patients with stage III colorectal cancer treated with 5-FU + LV (FLV) alone, or in combination with oxaliplatin (FLOX) according to the Nordic bolus regimen. The aim of the present study was to determine the association between expression of the folate-associated genes ABCC3, MTHFD2, SLC19A1, SLC25A32, SLC46A1, and TYMS and outcome of patients with metastatic colorectal cancer subjected to palliative chemotherapy. Patients and Methods - A total of 290 patients treated with FLV (n = 113), FLOX (n = 102) or FLV + irinotecan (FLIRI, n = 75) were included. Relative gene expression (ΔCt) was determined in primary tumors by quantitative PCR and analyzed in relation to clinical benefit, based on RECIST criteria and 3-year progression-free survival (PFS). Analyses were conducted on the whole study group, and on subgroups based on tumor stage at primary surgery (subgroup 1, stage I-III; subgroup 2, stage IV). An ANOVA test was used to assess the relationship between expression and clinical benefit. A multivariate Cox proportional hazard model was applied to assess potential associations between genetic markers, clinical variables and PFS. A Stepwise model selection was used to identify a minimal set of variables associated with PFS. Results - Low expression of TYMS and MTHFD2, and high expression of ABCC3 was significantly associated with a clinical benefit in the whole group (p Conclusion - Expression of TYMS, the target enzyme of 5-FU, was strongly associated with clinical benefit in the whole group, whereas expression of TYMS and the folate transporters SLC25A32, and ABCC3 was associated with PFS in the subgroups (stage I-III and stage IV), respectively. The prospective global phase III study AGENT is presently conducted on patients with advanced colorectal cancer, to determine whether expression of these genes can predict response to 5-FU-based chemotherapy that includes LV or the novel folate arfolitixorin. Citation Format: Yvonne Wettergren, Elisabeth Odin, Goran Carlsson, Pushpa Saksena, Anders Edsjo, Alessandro Di Cara, Roger Tell, Bengt Gustavsson. Tumoral expression of folate-associated genes is associated with progression-free survival of patients with advanced colorectal cancer [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 346.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80177471","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-665
J. Srovnal, Monika Vidlarova, E. Berta, P. Prasil, P. Kouřilová, J. Chudáček, M. Hajdůch
Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival rate of 21%. New treatment options are thus required, and the endogenous cannabinoid system is a potential new therapeutic target. We therefore analysed the expression of cannabinoid 1 and 2 receptor (CB1 and CB2) genes in NSCLC tissue and its influence on survival following radical surgery. Method: CB1 and CB2 gene expression in tumor tissue samples collected from 100 NSCLC patients was analysed using the quantitative real-time polymerase chain reaction. Since gene expression may not correlate with protein production, the presence of the CB2 protein was validated by immunohistochemistry. CB2 gene expression was correlated with disease stage, the presence of lymph node and distant metastases, tumor size, tumor grade, and survival. Result: Patients with tumors expressing CB2 gene had significantly longer overall survival (OS) (p<0.001), cancer-specific survival (CSS) (p=0.002), and disease-free survival (DFS) (p<0.001). They also had less advanced disease stage (p=0.047) and fewer lymph node metastases (p=0.011) at the time of surgery. A multivariate analysis showed that CB2 tumor tissue gene expression was a positive prognostic factor for OS (Hazard ratio (HR) = 0.402, p=0.013), CSS (HR=0.344, p=0.025), and DFS (HR=0.274, p=0.003). CB1 gene expression had no effect on survival. CB1 and CB2 gene expression was detected in 50% and 79.6% of the tumor tissue samples, respectively, and immunohistochemistry confirmed a correlation between CB2 gene expression and the presence of the CB2 protein in tumor tissues. Conclusion: In NSCLC patients undergoing radical surgery, CB2 gene expression in tumor tissue is associated with less advanced disease stage, fewer lymph node metastases, and longer survival (OS, CSS, DFS). Acknowledgement: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132), Palacky University Olomouc (LF 2020_007), Technological Agency of the Czech Republic (TN01000013), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Monika Vidlarova, Emil Berta, Petr Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch. Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery [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 665.
背景:非小细胞肺癌(NSCLC)是癌症相关死亡的主要原因，其5年生存率为21%。因此需要新的治疗方案，内源性大麻素系统是一个潜在的新治疗靶点。因此，我们分析了大麻素1和2受体(CB1和CB2)基因在非小细胞肺癌组织中的表达及其对根治性手术后生存的影响。方法:采用实时定量聚合酶链反应(pcr)对100例非小细胞肺癌患者肿瘤组织中CB1、CB2基因表达进行分析。由于基因表达可能与蛋白质产生无关，因此通过免疫组织化学验证了CB2蛋白的存在。CB2基因表达与疾病分期、淋巴结和远处转移、肿瘤大小、肿瘤分级和生存率相关。结果:表达CB2基因的肿瘤患者的总生存期(OS) (p<0.001)、肿瘤特异性生存期(CSS) (p=0.002)和无病生存期(DFS) (p<0.001)明显延长。在手术时，他们也有更少的疾病晚期(p=0.047)和更少的淋巴结转移(p=0.011)。多因素分析显示，CB2肿瘤组织基因表达是OS(危险比(HR) = 0.402, p=0.013)、CSS (HR=0.344, p=0.025)和DFS (HR=0.274, p=0.003)的阳性预后因素。CB1基因表达对生存率无影响。在50%和79.6%的肿瘤组织样本中分别检测到CB1和CB2基因表达，免疫组化证实了CB2基因表达与肿瘤组织中CB2蛋白的存在之间的相关性。结论:在接受根治性手术的非小细胞肺癌患者中，CB2基因在肿瘤组织中的表达与较低的疾病晚期、较少的淋巴结转移和较长的生存期(OS、CSS、DFS)相关。致谢:本研究得到了捷克共和国卫生部(NV18-03-00470)、捷克共和国教育、青年和体育部(LM2018132)、奥洛穆茨帕拉奇大学(LF 2020_007)、捷克共和国科技局(TN01000013)、欧洲区域发展基金(ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868)和捷克共和国癌症研究中心的支持。引文格式:Josef sronnal, Monika Vidlarova, Emil Berta, peter Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch。大麻素受体2肿瘤组织基因表达正影响肺癌根治术后的生存[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要第665期。
{"title":"Abstract 665: Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery","authors":"J. Srovnal, Monika Vidlarova, E. Berta, P. Prasil, P. Kouřilová, J. Chudáček, M. Hajdůch","doi":"10.1158/1538-7445.AM2021-665","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-665","url":null,"abstract":"Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival rate of 21%. New treatment options are thus required, and the endogenous cannabinoid system is a potential new therapeutic target. We therefore analysed the expression of cannabinoid 1 and 2 receptor (CB1 and CB2) genes in NSCLC tissue and its influence on survival following radical surgery. Method: CB1 and CB2 gene expression in tumor tissue samples collected from 100 NSCLC patients was analysed using the quantitative real-time polymerase chain reaction. Since gene expression may not correlate with protein production, the presence of the CB2 protein was validated by immunohistochemistry. CB2 gene expression was correlated with disease stage, the presence of lymph node and distant metastases, tumor size, tumor grade, and survival. Result: Patients with tumors expressing CB2 gene had significantly longer overall survival (OS) (p<0.001), cancer-specific survival (CSS) (p=0.002), and disease-free survival (DFS) (p<0.001). They also had less advanced disease stage (p=0.047) and fewer lymph node metastases (p=0.011) at the time of surgery. A multivariate analysis showed that CB2 tumor tissue gene expression was a positive prognostic factor for OS (Hazard ratio (HR) = 0.402, p=0.013), CSS (HR=0.344, p=0.025), and DFS (HR=0.274, p=0.003). CB1 gene expression had no effect on survival. CB1 and CB2 gene expression was detected in 50% and 79.6% of the tumor tissue samples, respectively, and immunohistochemistry confirmed a correlation between CB2 gene expression and the presence of the CB2 protein in tumor tissues. Conclusion: In NSCLC patients undergoing radical surgery, CB2 gene expression in tumor tissue is associated with less advanced disease stage, fewer lymph node metastases, and longer survival (OS, CSS, DFS). Acknowledgement: This study was supported by Ministry of Health of the Czech Republic (NV18-03-00470), Ministry of Education, Youth and Sport of the Czech Republic (LM2018132), Palacky University Olomouc (LF 2020_007), Technological Agency of the Czech Republic (TN01000013), European Regional Development Fund (ENOCH CZ.02.1.01/0.0/0.0/16_019/0000868) and Cancer Research Czech Republic. Citation Format: Josef Srovnal, Monika Vidlarova, Emil Berta, Petr Prasil, Pavla Kourilova, Josef Chudacek, Marian Hajduch. Cannabinoid receptor 2 tumor tissue gene expression positively affects lung cancer survival following radical surgery [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 665.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83116081","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-503
G. Vainer, Ghadeer Zatara, Lingkang Huang, K. Emancipator, S. Nuti
{"title":"Abstract 503: Analytical comparison of a PD-L1 22C3 antibody LDT protocol on the BenchMark XT and PD-L1 IHC 22C3 pharmDx: Analysis of pan-tumor and esophageal cancer samples","authors":"G. Vainer, Ghadeer Zatara, Lingkang Huang, K. Emancipator, S. Nuti","doi":"10.1158/1538-7445.AM2021-503","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-503","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77823094","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-477
M. Yu, Ting Wang, Kelly T Carter, K. Baker, M. Redman, Kathy Vickers, L. Dzubinski, R. Schoen, W. Grady
{"title":"Abstract 477: Elevated EVL methylation level in the normal colon mucosa is a potential risk biomarker for developing metachronous polyps","authors":"M. Yu, Ting Wang, Kelly T Carter, K. Baker, M. Redman, Kathy Vickers, L. Dzubinski, R. Schoen, W. Grady","doi":"10.1158/1538-7445.AM2021-477","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-477","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81405259","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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-536
R. Cutts, M. Coakley, I. Garcia-Murillas, L. Ulrich, K. Howarth, Warren Emmett, M. Perry, P. Ellis, C. Knape, S. Johnston, A. Ring, S. Russell, A. Evans, A. Skene, D. Wheatley, M. Dowsett, I. Smith, N. Turner
{"title":"Abstract 536: Molecular residual disease detection in early stage breast cancer with a personalized sequencing approach","authors":"R. Cutts, M. Coakley, I. Garcia-Murillas, L. Ulrich, K. Howarth, Warren Emmett, M. Perry, P. Ellis, C. Knape, S. Johnston, A. Ring, S. Russell, A. Evans, A. Skene, D. Wheatley, M. Dowsett, I. Smith, N. Turner","doi":"10.1158/1538-7445.AM2021-536","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-536","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89930577","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}
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