bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 400: Digital PCR combined with melting curve analysis for highly multiplexed genotyping
Authors: Tanaka Junko , Nakagawa Tatsuo , Shiratori Akiko , Shimazaki Yuzuru , Harada Kunio , Uematsu Chihiro , Kohara Yoshinobu , Takai Erina , Yachida Shinichi 
Published: August 2019

Abstract
Background
Digital PCR (dPCR) is a promising method for liquid biopsies and is able to quantify nucleic acids more sensitively than real-time PCR. However, dPCR has a large fluctuation in the fluorescence intensity of the droplets or wells due to insufficient PCR in the small partitions, limiting the multiplexing capability of using the fluorescence intensity. In this study, we propose a new measurement method that combines dPCR with melting curve analysis for highly multiplexed genotyping.
Methods
A sample is digitized into a silicon chip with up to ~104 wells in which asymmetric PCR was performed to obtain more single-stranded amplicons that are complimentary to molecular beacon probes. Fluorescence images were captured while controlling the temperature of the chip, and melting curve was measured for each well. Then, genotyping was performed by using the fluorescence intensity, dye color of the probe, and melting temperature (Tm). Because the Tm of the PCR products does not considerably depend on the amplification efficiency of PCR, genotyping accuracy is improved by using Tm values, enabling highly multiplexed genotyping.
Results
The concept was confirmed by measuring wildtype KRAS and its mutants, G12D, G12R, G12V, and G13D. The results showed that the peaks of the Tm distributions of the DNA groups were 69.2°C and 62.8°C for the wildtype and G13D with the first color dye (HEX), in addition to 66.9°C, 63.5°C, and 59.1°C for G12R, G12D, and G12V, respectively, with the second color dye (FAM). By combining the fluorescence intensities for HEX, FAM and the Tm values, the wildtype and mutant groups were clearly identified and able to be quantified. Furthermore, genotyping of cfDNA of pancreatic cancer patients was successfully performed by this method.
Conclusion
We have proposed a new measurement method that combines dPCR with melting curve analysis, and successfully performed the multiplexed genotyping assay. To our knowledge, this is the first demonstration of genotyping of five DNA groups with a single mutation of cancer-related genes by combining dPCR with melting curve analysis.
Citation Format: Junko Tanaka, Tatsuo Nakagawa, Akiko Shiratori, Yuzuru Shimazaki, Kunio Harada, Chihiro Uematsu, Yoshinobu Kohara, Erina Takai, Shinichi Yachida. Digital PCR combined with melting curve analysis for highly multiplexed genotyping [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 400.
Abstract 4003: Colon sessile serrated polyps associate with endometrial polyps
Authors: Brim Hassan , Tarjoman Taraneh , Ganjali Shirin , Azam Saman , Farsi Negin , Lee Edward , Shokrani Babak , Aduli Farshad , Williams Carla , Laiyemo Adeyinka , Soleimani Akbar , Sherif Zaki , Nouraie Mehdi syed , Ashktorab Hassan 
Published: August 2019

Abstract
Background: Colon and endometrial polyps are current health issues and their incidences are on the rise. Due to conflicting reports of higher colon polyps in patients with endometrial polyps, we aimed to evaluate if there is such an association in African Americans, a population at high risk for colorectal cancer.
Method: We retrospectively reviewed all female patients who had endometrial (EN) presentations (n=3,600) and colonoscopy (n=14,888) at Howard University Hospital from January 2004 to December 2015. We selected cases with endometrial poly and control without this diagnosis who underwent colonoscopy. Clinical [Body Mass Index (BMI), diabetes (DM), hypertension (HTN), Tamoxifen intake, age] and pathological (histology, location, type of lesions) features of Cases and Controls were collected. Association between EN and colon polyp was tested using multivariable logistic regression analysis. We excluded the patients with endometrial cancer.
Results: We recruited 664 cases and 118 controls. Cases were statistically significant older (median age of 60 vs. 57 in controls) and had higher rates of smoking and DM than controls. However, the overall colon polyp prevalence in the two groups was not statistically different (54% vs 52% in controls and cases, respectively). In subgroups of subject with colon polyp, sigmoid and rectal polyps were more prevalent in controls than cases. Sessile serrated polyps/adenomas (SSPs) were more frequent in cases (8% vs. 2%, p=0.03) while benign mucosa was more so in controls. Whether considering the overall study population or just those with colon polyps, SSPs lesions associated with an Odds Ratio of 4.6 (p=0.02) for EN polyp occurrence, after adjusting for confounder.
Conclusion: Our study shows that the overall colon polyp’s prevalence was similar in endometrial polyp patients compared to endometrial-polyp free controls. However, a significant association between SSP with endometrial polyps was noted. Females with colon lesions of the SSP type might benefit from a screening for endometrial polyp in an age-independent manner.
Note: This abstract was not presented at the meeting.
Citation Format: Hassan Brim, Taraneh Tarjoman, Shirin Ganjali, Saman Azam, Negin Farsi, Edward Lee, Babak Shokrani, Farshad Aduli, Carla Williams, Adeyinka Laiyemo, Akbar Soleimani, Zaki Sherif, Mehdi syed Nouraie, Hassan Ashktorab. Colon sessile serrated polyps associate with endometrial polyps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4003.
Abstract 4006: Effect of Prior Cancer on Trial Eligibility and Treatment Outcomes in Nasopharyngeal Carcinoma: Implications for Clinical Trial Accrual
Authors: Wang Ya-Qin , Lv Jia-Wei , Tang Ling-Long , Du Xiao-Jing , Chen Lei , Li Wen-Fei , Liu Xu , Guo Ying , Lin Ai-Hua , Mao Yan-Ping , Sun Ying , Chen Yu-Pei , Ma Jun 
Published: August 2019

Abstract
Background: In cancer trials, prior cancer is a common exclusion criterion. We evaluated the characteristics of prior cancer exclusion criteria in nasopharyngeal carcinoma (NPC) trials and determined its prognostic effect on patients with NPC.
Methods: We reviewed NPC trials for prior cancer exclusion criteria. Then we estimated the effect of prior cancer among NPC patients using the Surveillance, Epidemiology, and End Results database. Propensity score-matching was used to compensate for differences in baseline characteristics between patients with and without prior cancer.
Results: There were 109 clinical trials involving 10,437 patients; 49 trials (45%) excluded patients with prior cancer. Prior cancer exclusion was more common in recent or phase III trials. We identified 10,195 NPC patients; 6.2% had prior cancer. More than 70% of these cancers were in situ/localized/regional and diagnosed relatively close to the NPC diagnosis (median 3.3 years). Patients with certain prior cancer type (prostate, breast, gynecological, hematological), time of diagnosis (&gt;5 years ago), or stage (in situ/localized) did not have inferior survival compared with patients with no prior cancer. We tested one form of prior cancer exclusion criteria in an NPC cohort resembling a modern trial population: it did not adversely affect overall and NPC-specific survival.
Conclusions: Many NPC trials excluded patients with prior cancer, which impacts trial accrual and generalizability. Our findings suggest that broader inclusion in trials of patients with NPC with prior cancer might not affect trial outcomes. More research is needed to understand the appropriateness of this exclusion policy across cancer types and trials.
Citation Format: Ya-Qin Wang, Jia-Wei Lv, Ling-Long Tang, Xiao-Jing Du, Lei Chen, Wen-Fei Li, Xu Liu, Ying Guo, Ai-Hua Lin, Yan-Ping Mao, Ying Sun, Yu-Pei Chen, Jun Ma. Effect of Prior Cancer on Trial Eligibility and Treatment Outcomes in Nasopharyngeal Carcinoma: Implications for Clinical Trial Accrual [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4006.
Abstract 4008: Association of lung cavitation development with apatinib treatment outcomes in advanced gastric and NSCLC patients with multichemotherapy failure
Authors: Jiang Man , Zhang Chuantao , Liu Dong , Zhou Na , Wang Yongjie , Hou Helei , Li Tianjun , Lv Hongying , Zhu Jingjuan , Zhang Chuanyu , Zhang Xiaochun 
Published: August 2019

Abstract
Purpose:
Patients who receive antiangiogenic agents commonly develop cavitation in their lung lesions. This symptom has also been found in apatinib-treated patients with lung tumors. The present study evaluated the frequency and clinical outcomes of patients who developed tumor cavitation following apatinib treatment.
Experimental Design:
This was a retrospective study of 189 patients with lung tumors who were treated with 250 mg per day of apatinib between February 1, 2015, and May 19, 2017. Clinical data were retrieved from their medical records, and chest imaging findings were documented. Survival data were analyzed with Kaplan-Meier estimates and were compared with a log-rank test. OR values were analyzed for the effect factor of cavitation development.
Results:
Cavitation development showed a benefit for patients on apatinib therapy regardless of whether they had primary or metastatic lung cancer. For patients without cavitation, metastatic lung cancer had greater 6-month LRC, PFS and OS rates than did primary lung cancer. No significant association was found between histological type and survival analysis in apatinib-treated NSCLC patients. Increased CEA levels promoted PFS in patients on apatinib who developed cavitation. However, changes in CEA values did not predict LRC, OS or PFS in patients who developed no cavitation. OR analysis showed that increased CEA levels were a risk factor for cavitation development.
Interpretation:
This was a retrospective real-world study approved by the ethics committee of the Affiliated Hospital of Qingdao University. Patients with advanced or metastatic gastric cancer and NSCLC who had progressed or relapsed after undergoing at least two lines of systemic therapy in accordance with NCCN guidelines and had never received antiangiogenic therapy were included.
Conclusions:
Lung cavitation development is common with apatinib therapy and is a potential prognostic biomarker. CEA is not a prognostic biomarker but is a prospective biomarker for lung cavitation in apatinib-treated patients.
Note: This abstract was not presented at the meeting.
Citation Format: Man Jiang, Chuantao Zhang, Dong Liu, Na Zhou, Yongjie Wang, Helei Hou, Tianjun Li, Hongying Lv, Jingjuan Zhu, Chuanyu Zhang, Xiaochun Zhang. Association of lung cavitation development with apatinib treatment outcomes in advanced gastric and NSCLC patients with multichemotherapy failure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4008.
Abstract 4009: GLUT3 variant is associated withprognosis of patients with non-small cell lung cancer after surgical resection
Authors: Lee Shin Yup , Do Sook Kyung , Choi Sun Ha , Choi Jin Eun , Kang Hyo Gyoung , Hong Mi Jeong , Baek Dong Won , Yoo Seung Soo , Son Ji Woong , Park Jae Yong 
Published: August 2019

Abstract
This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C&gt;T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04-2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18-2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C&gt;T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15-5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.
Citation Format: Shin Yup Lee, Sook Kyung Do, Sun Ha Choi, Jin Eun Choi, Hyo Gyoung Kang, Mi Jeong Hong, Dong Won Baek, Seung Soo Yoo, Ji Woong Son, Jae Yong Park. GLUT3 variant is associated withprognosis of patients with non-small cell lung cancer after surgical resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4009.
Abstract 4019: High TERT expression in NSCLC is associated with poor prognosis
Authors: Li Tianhong , Ma Weijie , Li Qianping , Wei Sixi , Wang Tao , Xiang Jingyi , Liu Cheng 
Published: August 2019

Abstract
Background: Activation of human telomerase reverse transcriptase (TERT) has been linked to tumorigenesis and aggressive tumor behavior. This study was undertaken to evaluate if TERT expression was correlated with clinicopathological parameters and survival in patients with non-small cell lung cancer (NSCLC).
Methods: TMA slides made from 254 NSCLC patients (cohort 1 and cohort 2), including 127 adenocarcinoma (LUAD), 78 squamous carcinomas (LUSC) and 46 other types, were included. TMA Formalin-fixed and paraffin-embedded (FFPE) tissue sections were stained using the immunohistochemistry stain (IHC). The percentage of positive nuclei was determined for each case and the cut-off value was set as 5%, 20% and 50% positive tumor cells. TERT expression levels were analyzed for associations with patient survival rates and clinicopathological parameters (such as age, gender, tumor grade, tumor stage, metastasis). Survival analysis was performed using the Kaplan-Meier method.
Results: TERT was positive in 199/254 (78%) of the samples. High TERT expression was seen in tumor specimens compared with normal adjunct tissues (p &lt; 0.001). Kaplan-Meier curves indicated that high TERT expression was significantly associated with poor overall survival in NSCLC patients (p &lt; 0.001 and p &lt; 0.0001, 20% and 50% cut-off, respectively). Multivariate analysis of survival demonstrated that TERT expression at 50% cutoff was an independent prognostic factor for NSCLC patients (HR = 0.1461, 95% CI: 0.0862-0.2475, p &lt; 0.0001). High TERT expression was also associated with short survival of LUSC and LUAD patients at 50% cutoff (p &lt; 0.0001). No significant association with OS was observed at 5% cutoff. There was also significant correlation between TERT expression with metastasis but no correlation with clinical stage, histological type and tumor differentiation.
Conclusion: Our study showed that high TERT expression is present in 78% of NSCLC tumors and is associated with poor prognosis. TERT may serve as a prognostic biomarker and novel drug target for NSCLC.
Citation Format: Tianhong Li, Weijie Ma, Qianping Li, Sixi Wei, Tao Wang, Jingyi Xiang, Cheng Liu. High TERT expression in NSCLC is associated with poor prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4019.
Abstract 4028: Tenascin C in gastric cancer stroma is a predictive marker for postoperative prognosis
Authors: Kikuchi Hirotoshi , Murakami Tomohiro , Kawata Sanshiro , Hirotsu Amane , Matsumoto Tomohiro , Ozaki Yusuke , Hiramatsu Yoshihiro , Kamiya Kinji , Morita Yoshifumi , Sakaguchi Takanori , Konno Hiroyuki , Takeuchi Hiroya 
Published: August 2019

Abstract
Background: Tenascin C, a glycoprotein in the extracellular matrix is reportedly associated with poor clinical outcome in several malignancies. We have previously reported that tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis (Br J Cancer 117:1360-70, 2017). In this study, we evaluated the clinicopathological and prognostic significance of tenascin C expression in gastric cancer stroma.
Materials and methods: Expression levels of tenascin C protein were immunohistochemically analyzed in 176 primary gastric cancer samples. Tenascin C staining intensity and relativity were classified into four scores and two groups, respectively. The correlation of the tenascin C staining intensity and relativity with clinicopathological factors, postoperative overall survival (OS) and disease-free survival (DFS) were analyzed.
Results: There were positive correlations between the tenascin C staining intensity or relativity and tumor depth, lymphatic invasion, venous invasion, lymph node metastasis, pathological stage, high preoperative carcinoembryonic antigen (CEA)&gt;5ng/ml, and high preoperative carbohydrate antigen (CA19-9) &gt;37U/ml. Multivariate analysis revealed that high tenascin C staining intensity significantly correlated with tumor invasion into the muscularis propria (p=0.015) and venous invasion (p=0.042), and that high tenascin C staining relativity correlated with venous invasion (p=0.013). Gastric cancer patients with high tenascin C staining intensity had significantly shorter postoperative OS (p&lt;0.001), whereas tenascin C staining relativity did not correlate with postoperative OS (p=0.05). High tenascin C staining intensity and relativity significantly correlated with shorter postoperative DFS (p&lt;0.001 and 0.005, respectively). Cox proportional hazard model identified high tenascin C staining intensity as an independent prognostic factor for poor postoperative OS (hazard ratio (HR): 13.16, 95% confidence interval (CI): 1.362-125.000, p=0.026) and DFS (HR: 6.02, 95%CI: 1.538-23.810, p=0.010).
Conclusions: Tenascin C protein expression in primary tumor stroma was identified as a predictive marker for postoperative prognosis in patients with gastric cancer.
Citation Format: Hirotoshi Kikuchi, Tomohiro Murakami, Sanshiro Kawata, Amane Hirotsu, Tomohiro Matsumoto, Yusuke Ozaki, Yoshihiro Hiramatsu, Kinji Kamiya, Yoshifumi Morita, Takanori Sakaguchi, Hiroyuki Konno, Hiroya Takeuchi. Tenascin C in gastric cancer stroma is a predictive marker for postoperative prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4028.
Abstract 4035: Protein tyrosine kinase 7 (PTK7) biomarker analysis in patients (pts) treated with PF-06647020, a PTK7 antibody-drug conjugate (ADC), in a phase I dose expansion study
Authors: Jackson-Fisher Amy , Mehra Navi , Gianani Roberto , Whalen Pamela , Vizcarra Pamela , Deng Shibing , McComish Stephen , Xin Xiaohua , Powell Eric L. 
Published: August 2019

Abstract
Background: PF-06647020, an ADC comprising a humanized monoclonal antibody against PTK7, a cleavable valine-citrulline linker, and an auristatin payload, is being investigated in an ongoing Phase I clinical trial in pts with advanced solid tumors. We hypothesized that response to a PTK7-directed ADC would correlate with PTK7 expression in the pts tumor. We report preliminary baseline PTK7 expression in pts tumors and clinical response using a novel CLIA validated laboratory developed test (LDT).
Methods: We developed and validated an LDT comprising an anti-PTK7 immunohistochemistry assay with digital tissue analysis using Flagship Biosciences Inc’s cTA® platform to detect membrane-associated PTK7 in formalin-fixed paraffin embedded (FFPE) epithelial malignancies of ovary, breast and lung. Tumor samples were immunolabeled with the LDT and image analysis was applied to derive a digital H-score. Specifically the digital image annotation included desired regions of analysis (ROA) and excluded regions not of interest. The cTA® platform identified each cell in a given ROA and quantified an overall H-score for malignant epithelial cell membranes immunolabeled for PTK7. Non-small cell lung cancer (NSCLC) pts with H-scores ≥ 56.8 were eligible for enrollment whereas ovarian cancer (OVCA) pts were enrolled unselected. Triple negative breast cancer (TNBC) pts were initially enrolled unselected, but after review a requirement for H-scores ≥ 92.8 was implemented for enrollment.
Results: PTK7 IHC was performed on baseline FFPE samples from 69 pts and digital H-scores were generated (Table 1). An additional 7 pt samples were not amenable to analysis with the cTA® platform.
Conclusions: A novel CLIA validated LDT was developed and implemented to assess PTK7 baseline levels in FFPE tumors from pts treated with PF-06647020. Clinical responses tended to correlate with H-scores that were higher than the mean for each tumor type.
Table 1.PTK7 digital H-scores in Phase I dose expansionNumber of SamplesMinimum H-scoreMaximum H-scoreMean H-scoreMean H-score of Non-respondersMean H-score of RespondersOVCA31120089.280.2111.2NSCLC1993287167.8159.2200.3TNBC1953258159.2147.0224.3
Citation Format: Amy Jackson-Fisher, Navi Mehra, Roberto Gianani, Pamela Whalen, Pamela Vizcarra, Shibing Deng, Stephen McComish, Xiaohua Xin, Eric L. Powell. Protein tyrosine kinase 7 (PTK7) biomarker analysis in patients (pts) treated with PF-06647020, a PTK7 antibody-drug conjugate (ADC), in a phase I dose expansion study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4035.