bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3125: KCNQ1 expression is a strong prognostic biomarker for disease recurrence in stage II and III colon cancer
Authors: den Uil Sjoerd H. , Coupe Veerle M.H. , Linnekamp Janneke F. , van den Broek Evert , Goos Jeroen A.C.M. , Delis-van Diemen Pien M. , Belt Eric J.T. , van Grieken Nicole C.T. , Scott Patricia M. , Vermeulen Louis , Medema Jan Paul , Bril Herman , Stockmann Hein B.A.C. , Cormier Robert T. , Meijer Gerrit A. , Fijneman Remond J. 
Published: July 2016

Abstract
Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at high risk of recurrence and stage III patients at low risk of recurrence are key unmet clinical needs. We previously identified KCNQ1 as a tumour suppressor gene of which loss of expression was associated with poor survival in patients with CRC liver metastases. The present study aimed to examine the prognostic value of KCNQ1 in stage II and III colon cancer patients.
Methods: KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. KCNQ1 protein expression was evaluated by immuno-histochemistry on tissue microarrays of 386 stage II and III colon cancer patients.
Results: Low KCNQ1 mRNA expression in microsatellite stable (MSS) stage II colon cancers was associated with poor disease free survival (DFS) (HR 3.35; 95% CI 1.16-9.66; p&lt;0.05). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in MSS stage II (HR 3.82; 95% CI 2.04-7.14; p&lt;0.0001), MSS stage III (HR 2.93; 95% CI 1.70-5.02; p = 0.0001) and MSI stage III colon cancers (HR 5.06; 95% CI 1.07-23.89; p&lt;0.05). Multivariate analysis demonstrated KCNQ1 to have independent prognostic value in addition to established clinicopathological parameters such as angioinvasion, nodal stage en MSI-status.
Conclusion: We conclude that KCNQ1 is a strong prognostic biomarker for prediction of disease recurrence (HR∼4) and may aid stratification of patients with stage II MSS colon cancer and stage III MSI CRC for adjuvant chemotherapy. Because KCNQ1 protein expression is determined by immuno-histochemistry, this biomarker can be implemented in standard clinical care using existing workflows.
Citation Format: Sjoerd H. den Uil, Veerle M.H. Coupe, Janneke F. Linnekamp, Evert van den Broek, Jeroen A.C.M. Goos, Pien M. Delis-van Diemen, Eric J.T. Belt, Nicole C.T. van Grieken, Patricia M. Scott, Louis Vermeulen, Jan Paul Medema, Herman Bril, Hein B.A.C. Stockmann, Robert T. Cormier, Gerrit A. Meijer, Remond J. Fijneman. KCNQ1 expression is a strong prognostic biomarker for disease recurrence in stage II and III colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3125.
Abstract 3130: Adiponectin, Leptin, IGF1 and TNFα serum biomarker as noninvasive diagnosis of colon adenoma
Authors: Ashktorab Hassan , Soleimani Akbar , Nichols Alexandra , Sodhi Komal , Kannan Lakshmi , Adeyinka Laiyemo , Nouraie Mehdi , Brim Hassan 
Published: July 2016

Abstract
Background and Aim: The potential role of Adiponectin, Leptin, IGF1 and TNFα as biomarker in colon adenoma has not been studied. Therefore, we investigated the blood serum levels of these biomarkers in colorectal adenoma.
Method: The case-control study consisted of 198 African American patients with colon adenoma (cases) and 198 healthy individuals (controls) at Howard University Hospital. We used Elisa for biomarkers detection. Statistical analysis was performed by t-test and multivariate logistic regression.
Results: The differences in median leptin, Adiponectin, IGF1 and TNFα levels between control and case groups (6.7 vs.16.4), (11.3 vs.46.0), (4.5 vs.12.9) and (71.4 vs. 130.8) were statistically significant (p&lt;0.05), respectively. In a multivariate model, the odds ratio (ORs) for Adiponectin, TNFα and IGF1 were 2.0 (95% CI = 1.6-2.5; P≤0.001), 1.5 (95% CI = 1.5- 2.0; P 0.004) and 1.6 (95% CI = 1.3-2.0; P≤ 0.001), respectively. There were positive correlations between serum Adiponectin and IGF1 concentrations with age (r = 0.17, P≤ 0.001 and r = 0.13, P = 0.009), also between TNFα, IGF1 and Leptin concentration with Body Mass Index (BMI) (r = 0.44, P≤ 0.001 and r = 0.11, P = 0.03; r = 0.48, P≤0.001), respectively. There was a negative correlation between Adiponectin concentration and BMI (r = -0.40, P≤0.001), respectively.
Conclusion: These data support the hypothesis that serum Adiponectin, IGF1 and TNFα are risk biomarkers for noninvasive detection of colorectal adenomas.
Citation Format: Hassan Ashktorab, Akbar Soleimani, Alexandra Nichols, Komal Sodhi, Lakshmi Kannan, Laiyemo Adeyinka, Mehdi Nouraie, Hassan Brim. Adiponectin, Leptin, IGF1 and TNFα serum biomarker as noninvasive diagnosis of colon adenoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3130.
Abstract 315: Potential role of androgen receptor in aromatase inhibitor resistance
Authors: Hunt Caleb , Lock Sarah E. , Shannon Cynthia E. , Varela-Gonzalez Nichole M. , Larsen Randolph K. , Schech Amanda J. 
Published: July 2016

Abstract
Clinical assessment of breast cancer tumors has shown that androgen receptor (AR) is expressed in more than 75% of cases, independent of molecular subtype. Specifically, clinical studies have shown that estrogen receptor (ER) and AR discordance correlates with endocrine resistance. Preclinical studies show that downregulation of ER results in a lack of estrogen mediated growth which is concurrent with upregulation of AR and its mediated gene targets. In addition, forced expression of AR was shown to induce resistance to tamoxifen, even when estrogen receptor was still expressed. Furthermore, ER positive breast cancer cells made resistant to tamoxifen express higher levels of AR and show sensitivity to abiraterone acetate. Together, these results implicate AR in endocrine resistance and suggest AR as a potential therapeutic target in a subset of these endocrine resistant cancers. The aim of this study was to better understand the role of AR in aromatase inhibitor (AI) resistance through the use of cell lines made resistant to AI through xenograft mouse modeling. In this study, MCF7 cells, MCF7 cells transfected with the human aromatase gene (MCF7Ca), and their aromatase inhibitor (AI) resistant counterparts, were analyzed for changes in AR and ER expression by qPCR and Western blot. Sensitivity of these cells to AR targeting agents was assessed by MTT assay. MCF7Ca cells displayed decreased expression of AR and increased expression of ER when compared to MCF7 cells. AI-resistant cell lines displayed modulation of ER and AR expression when compared to their AI-sensitive counterparts. Upregulation of AR was accompanied with increased AR transcriptional activity, as demonstrated by increased expression of PSA. Treatment of AI-resistant cells with AR targeting agents displayed increased sensitivity when compared to AI-sensitive cells. Together, these results suggest that upregulation of AR may contribute to AI-resistance, and that targeting AR in AI-resistant breast cancer may have therapeutic relevance.
Citation Format: Caleb Hunt, Sarah E. Lock, Cynthia E. Shannon, Nichole M. Varela-Gonzalez, Randolph K. Larsen, Amanda J. Schech. Potential role of androgen receptor in aromatase inhibitor resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 315.
Abstract 3158: Prostate cancer derived biomarkers within platelets have the ability to predict therapeutic response in castration resistant patients
Authors: Tjon-Kon-Fat Lee-Ann , Lundholm Marie , Wurdinger Thomas , Thellenberg-Karlsson Camilla , Widmark Anders , Wikström Pernilla , Nilsson Jonas 
Published: July 2016

Abstract
Background: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. In this article a novel platform for circulating biomarker analysis has been used to follow cancer-derived transcripts implicated in therapy resistance.
Method: The platelet population of blood samples and QRT-PCR were used to identify selected biomarkers in CRPC patient's prior chemo- or androgen synthesis (AS)-directed therapies. The association between biomarker statuses (positive vs. negative) and therapy response, progression-free survival (PFS) and overall survival (OS) was examined.
Results: 40 patients received either docetaxel (n = 17) or AS-directed (n = 23) therapy, with a therapy response rate of 29% respectively 48%. The cancer-associated biomarkers were present within the platelet fraction. Analyzing these biomarkers in the chemotherapy group were associated with a short OS (p = 0.025). In the AS-directed group, the biomarkers were associated with shorter PFS (p = 0.015), and with an increased risk of therapy failure (HR: 5,5; p = 0,023), as well as short OS (p = 0.012).
Conclusions: Analyzing circulating biomarkers in the platelet population enables us to predict who will benefit from AS-directed therapy with high accuracy, and platelet based analysis of cancer derived biomarkers may be used in treatment stratification of patients scheduled for AS-directed therapies.
Citation Format: Lee-Ann Tjon-Kon-Fat, Marie Lundholm, Thomas Wurdinger, Camilla Thellenberg-Karlsson, Anders Widmark, Pernilla Wikström, Jonas Nilsson. Prostate cancer derived biomarkers within platelets have the ability to predict therapeutic response in castration resistant patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3158.
Abstract 3161: Development and implementation of a non-invasive NGS-based diagnostic test for precision medicine in prostate cancer
Authors: Du Pan , Wang Amy , Cheng Tak , Kuo Winston Patrick 
Published: July 2016

Abstract
The growth and survival of prostate cancer tumors relies primarily on the functioning of the androgen receptor (AR) signaling pathway. Recent studies suggested that the presence of AR-V7, a c-terminal truncated form of AR, in circulating tumor cells (CTCs) of patients with castration-resistant prostate cancer (CRPC) is associated with inherent and/or acquired resistance to enzalutamide and abiraterone, the stand of care androgen deprivation therapies in prostate cancer. A series of data also indicate that AR-Vs (eg, including AR-V7, ARv567es, AR-T878A, AR-F876L, and Arv567es) may drive resistance in CRPC. Expression of AR-Vs has been shown to correlate with disease progression and shortened survival and AR-V7 is most abundant in CRPC specimens. Considering that truncated ARs with C-terminal loss (splice variants) lack a functional LBD and are constitutively active, C-terminal AR-directed therapies may not be effective, and novels agents are needed that target mutated ARs including AR-Vs. Circulating tumor cell (CTC)-based AR-V7 tests are currently being tested in the clinic. However, nearly half of the CRPC patients do not have enough CTCs for AR-V7 test, raising the request for a complementary, non-CTC platform to detect AR variants as well as other resistance markers in circulation.
Here we report the successful development of a non-invasive, next generation sequencing-based diagnostics platform that offers comprehensive profiling of genomic alterations in prostate cancer, including splicing variants (such as AR-V7), point mutation, copy number, and translocation using biofluid samples (blood and urine) from CRPC patients. To the best of our knowledge, this is the first non-invasive diagnostic test that measures genetic alterations especially AR-V7 in all patients with prostate cancer, regardless of their status of CTC enumeration. The successful development and clinical validation of this test has potential to enable precision medicine in prostate cancer.
Citation Format: Pan Du, Amy Wang, Tak Cheng, Winston Patrick Kuo. Development and implementation of a non-invasive NGS-based diagnostic test for precision medicine in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3161.
Abstract 3162: Blood-based exosomal miRNAs as biomarkers for diagnosis and prognosis of clear cell renal cell cancer
Authors: Heinzelmann Joana , Baumgart Sophie , Hoelters Sebastian , Janssen Martin , Stöckle Michael , Junker Kerstin 
Published: July 2016

Abstract
Introduction & objectives: In previous studies we identified specific miRNA alterations in tumor tissues of clear cell renal cell cancer (ccRCC) with diagnostic and prognostic value relating to the presence of metastasis. For few years it has been known, that miRNAs are actively packed in exosomes which can be released into body fluids. Therefore, we hypothesize that in a simple blood based test we are able to use specific miRNA signatures as minimal invasive biomarkers for confirmation of the diagnosis and evaluation of the metastatic risk in ccRCC.
Materials & methods: Initially, exosomes were isolated from 1 ml serum of 10 ccRCC patients (metastatic and non metastatic tumors) and 10 healthy volunteers using appropriated exosome isolation kit protocol (Thermo Fisher Scientific). Quality of exosomes was proven using exosomal markers (CD63, CD81, Alix, Synthenin) and Nano Particle Tracking Analysis. Exosomal totalRNA was isolated using miRNeasy Mini Kit (Qiagen). For miRNA analyses total RNA was reverse transcribed using TaqMan Reverse Transcription Kit (Thermo Fisher Scientific), cDNA was preamplified using TaqMan® PreAmp Master Mix (Thermo Fisher Scientific) and real time PCR was performed using Gene Expression master mix (Thermo Fisher Scientific). Expression differences were calculated using REST Software and SPSS.
Results: We have shown that 1 ml serum is sufficient to analyze miRNA expression in exosomes. Exosomes isolated from serum exhibit high amount of exosomal markers and possess the typical exosomal size (30-120 nm). CcRCC serum samples are characterized by downregulation of several miRNAs (including miR-10b and miR451). Furthermore, specific miRNAs (including miR-30c) differentiate patients with or without metastases as well as healthy volunteers.
Conclusion: These initial data confirm our hypothesis that the tissue based miRNA signature could be used as biomarkers for detection of aggressive ccRCC analyzing exosomes from liquid biopsy. This minimal invasive blood based test is easy to handle in clinical practice and could be a powerful tool for early detection and monitoring of metastatic disease. To validate these results the expansion of the sample set is ongoing.
Citation Format: Joana Heinzelmann, Sophie Baumgart, Sebastian Hoelters, Martin Janssen, Michael Stöckle, Kerstin Junker. Blood-based exosomal miRNAs as biomarkers for diagnosis and prognosis of clear cell renal cell cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3162.
Abstract 3174: Colon cancer molecular subtypes: Concordance, effect on survival and selection of most representative preclinical models
Authors: Sztupinszki Zsófia , Győrffy Balázs 
Published: July 2016

Abstract
Introduction: Colon cancer is a genetically heterogeneous disease and there is an increasing need for more detailed classification of stage II and III patients. The NCCN guideline currently lists three FDA approved gene-expression based multi-gene prognostic tests for stage II-III colorectal cancer. However, it is undecided how many molecular subtype would most accurately describe these tumours. Here, we cross-validated known molecular subtypes for their concordance and capability to predict prognosis free survival. We utilized gene expression signatures to identify the most representative cell line model for each subtype.
Materials and methods: Using publicly available datasets from the GEO repository we established a database containing clinical and microarray data for 2,166 colon cancer patients. Gene expression measured on Affymetrix HG-U133A and HG-U133 Plus2.0 arrays was processed according to authors’ description for each classifier in R. We conducted a systematic review of the literature in order to identify gene-expression based classifiers. We assigned each sample for these classificators and then compared their potential to predict recurrence free survival.
Results: All together 22 different molecular subtypes were re-classified including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors). When comparing the methods the most concordant classifiers were MDA114 and DeSousa (Cramer's V = 0.711). The highest efficacy to predict progression free survival in stage II-III patients was achieved by Yuen (p = 3.9e-05, HR = 2.9), Marisa (p = 2.6e-05, HR = 2.6) and Chang (p = 9e-09, HR = 2.35). We also assigned 61 colon cancer cell lines from four independent studies to the closest molecular subtype.
Conclusion: In summary, here we present a comprehensive analysis of human colon cancer molecular subtypes by cross-validation using independent transcriptomic datasets.
Citation Format: Zsófia Sztupinszki, Balázs Győrffy. Colon cancer molecular subtypes: Concordance, effect on survival and selection of most representative preclinical models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3174.
Abstract 3179: Germline deletion of FH in hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
Authors: Vocke Cathy D. , Ricketts Christopher J. , Middelton Lindsay A. , Yang Youfeng , Linehan. W. Marston 
Published: July 2016

Abstract
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a familial cancer syndrome characterized by germline mutations in the fumarate hydratase (FH) gene that encodes the enzyme responsible for conversion of fumarate to malate in the Kreb's Cycle. HLRCC is associated with the development of cutaneous and uterine leiomyomas, and a highly aggressive form of type 2 papillary kidney cancer. HLRCC renal tumors can be extremely aggressive with patients demonstrating locally advanced or disseminated disease even when associated with small tumors 1-2 cm in size. Therefore, accurate identification of the “at risk” individuals is very important. In our experience, FH point mutations are identified in 90% of individuals that are clinically diagnosed with HLRCC, while in the remainder, FH may be inactivated by deletion or other causes. Several studies have reported complete deletions of the FH gene and a few have estimated the extent of these deletions and identified the additional genes that would be lost in conjunction with FH. Interestingly, families with complete FH deletion have demonstrated cutaneous and uterine leiomyomas but no families have yet been reported with evidence of kidney cancer. A single family has been identified that demonstrates a partial deletion resulting in the loss of exon 1, and in this case kidney cancer has identified within the family. In this study, patients with suspected HLRCC hereditary kidney cancer but no germline point mutation were enrolled on an NCI-IRB approved protocol and an Agilent custom high-definition comparative genomic hybridization (CGH) array was used to identify FH gene deletions. The assay identified complete germline deletion of a single copy of FH within seven suspected HLRCC patients deletion ranging from 249kb to 4.74Mb that in all cases resulted in a minimum addition loss of the KMO, OPN3, CHML, and WDR6 genes. All results were confirmed by CLIA approved tests and a further five new patients were identified by direct CLIA testing, including a novel partial deletion. In contrast to previous reports, seven out of twelve (58.3%) patients/families in our cohort demonstrated a personal or family history of HLRCC associated Type 2 papillary kidney cancer. In conclusion, complete or partial deletion of the FH gene is an infrequent but important cause of HLRCC and has no protective effect on the incidence of HLRCC associated type 2 papillary kidney cancer.
Citation Format: Cathy D. Vocke, Christopher J. Ricketts, Lindsay A. Middelton, Youfeng Yang, W. Marston Linehan. Germline deletion of FH in hereditary leiomyomatosis and renal cell carcinoma (HLRCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3179.
Abstract 3191: Molecular testing in lung cancer: Patient and caregiver experiences
Authors: King Jennifer C. , Rigney Maureen 
Published: July 2016

Abstract
Increasingly over the past decade, new targeted therapeutics and immunotherapies with associated companion diagnostics have been approved for the treatment of lung cancer. Lung cancer is often associated with elderly and lower socio-economic populations that may not have a high level of health literacy. As part of a comprehensive needs assessment survey of the lung cancer community, lung cancer patients and their caregivers were asked whether they or their loved ones had undergone molecular testing/biomarker testing as well as asked to report the history of oncologic drugs they had taken. Demographic information and additional cancer treatment history were also collected. Over 300 survey responses were collected. Interim analyses indicated that the majority (68%) of patients currently undergoing active treatment had received molecular testing to help determine their treatment plan. There was a clear improvement in testing rates over time with less than 30% of patients who had completed treatment reporting use of a molecular test. Importantly, there is still an educational gap that needs to be addressed as greater than 20% of patients and greater than 30% of loved ones, including the group who self-identified as the primary caregiver, reported that they did not know whether molecular testing had been performed. In addition, patients reported that they had not received EGFR mutation testing but had taken erlotinib, gefinitib, and/or afatinib. Final results will be presented as well as an analysis of factors that associate with lack of molecular testing. Taken together, these data indicate that there is a critical need for enhanced patient and caregiver education regarding molecular testing.
Citation Format: Jennifer C. King, Maureen Rigney. Molecular testing in lung cancer: Patient and caregiver experiences. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3191.