bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1134: RNAi screening of human kinome identified fibroblast growth factor receptor 4 (FGFR4) as potential molecular target in basal-like breast cancers (BLBC).
Authors: Tiong Kai Hung , Tan Boon Shing , Choo Heng Lungh , Radhakrishnan Ammu Kutty , Rosli Rozita , Cheong Soon-Keng , Leong Chee-Onn 
Published: August 2014

Abstract
Global gene expression profiling has uncovered previously unrecognized subsets of human breast cancer, including the so-called "triple-negative" or "basal-like" tumours (BLBC) characterized by estrogen/progesterone receptor negativity, lack of Her-2/Neu amplification and high frequency of p53 mutation. These refractory tumours therefore are insensitive to hormonal therapy or trastuzumab-based therapy, and thus confer a markedly poor prognosis relative to other subtypes. To date, little progress has been made to identify specific molecular pathways associated with these refractory cancers that may be effectively targeted for therapeutic purposes. Using a human kinome RNAi library screen, we show that knock-down of endogenous human FGFR4 (but not FGFR1-3) induces significant tumor-specific cell death in basal-like breast cancer cells. Further analysis reveals that FGFR4 mediates the BLBC cells survival through activation of AKT as knock-down of endogenous FGFR4 in MDA-MB-468 and HCC1937 cells significantly reduced AKT phosphorylation. Consistently, ectopic expression of a constitutively active myristoylated AKT completely abrogates the apoptosis induced by FGFR4 knock-down. Interestingly, both MDA-MB-468 and HCC1937 also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. RNAi-mediated silencing of FGF19 evidently suppresses the growth of these BLBC cells via AKT signalling as marked by diminished AKT phosphorylation following depletion of FGF19. Knockdown of FGF19 in addition triggers ERK1/2 activation to compensate for AKT signalling down-regulation in MDA-MB-468. Together, our results demonstrated the existence of a FGFR4-FGF19 autocrine loop which could potentially be developed as therapeutic target for future treatment of BLBC.
Citation Format: Kai Hung Tiong, Boon Shing Tan, Heng Lungh Choo, Ammu Kutty Radhakrishnan, Rozita Rosli, Soon-Keng Cheong, Chee-Onn Leong. RNAi screening of human kinome identified fibroblast growth factor receptor 4 (FGFR4) as potential molecular target in basal-like breast cancers (BLBC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1134. doi:10.1158/1538-7445.AM2013-1134
Abstract 1146: STK4 downregulation promotes tumor invasion/migration and is associated with poor prognosis in human colon cancer.
Authors: Lee Yu-Cheng , Yang Chia-Ning , Hsu Tai-I , Lu Pei-Jung 
Published: August 2014

Abstract
Colon cancer has high incidence rate in the world and the early stage of colon cancer can be cured by surgical therapy. However, it remains difficult to predict the prognostic outcome of colon cancer patients. STK4 is considered as a potential tumor suppressor, which plays an important role in Hippo pathway to control the organ size and the inhibition ability of cell-cell contact. The major aim of this study is focused on the investigation of prognostic value of STK4 in colon cancer. By immunohistochemistry assay, we examined the expression of STK4 in 140 pairs normal and tumor colon cancer specimens. The relationship between STK4 expression and clinicopathological factors as well as patient survival were analyzed and the results showed that STK4 was significantly downregulated in tumor tissues compared to their corresponding non-tumor part (P&lt;0.01) and that was significantly associated with tumor size (P=0.003), distal metastasis (P=0.03), disease recurrence and poor survival (P&lt;0.005). Moreover, loss of STK4 expression showed a significant poor outcome in colon cancer patients by univariate and multivariate analysis. These results indicated that there is a positive correlation in STK4 expression and prognosis and survival of colon cancer patients. Loss of STK4 expression displayed poor outcome. The conclusion is that STK4 can be used as a prognostic maker to predict patient survival and play a role in metastasis suppression of colorectal cancer.
Citation Format: Yu-Cheng Lee, Chia-Ning Yang, Tai-I Hsu, Pei-Jung Lu. STK4 downregulation promotes tumor invasion/migration and is associated with poor prognosis in human colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1146. doi:10.1158/1538-7445.AM2013-1146
Abstract 1147: Expression of ERO1L gene is poor prognostic factor for gastric cancer.
Authors: Seol So-Young , Lim Jae Yun , Yoon Sun Och , Hong Soon Won , Kim Jong Won , Choi Seung Ho , Cho Jae Yong 
Published: August 2014

Abstract
Gastric cancer is the second cause of cancer-related deaths worldwide. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. Molecular markers will be important in predicting patients’ outcomes and tailoring personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. We evaluated ERO1L significantly overexpressed in gastric cancer and ERO1L was very highly expressed in hypoxic condition. The other study has identified ERO1L as included in the small group of eight genes predicting poor survival of patients with pulmonary adenocarcinoma. To investigate the function of ERO1L gene in gastric cancer cell line (AGS, MKN1 and NCI-N87), we tested the effect of shRNA inhibition of ERO1L on gastric cancer cells. To determine the biologic role of ERO1L in regulating cancer cell proliferation, stable transfection of shRNA for ERO1L in gastric cancer cells. Our results showed that shERO1L decrease cell proliferation. Furthermore, Knock down expression by shERO1L have effects on regulating gastric cancer cell apoptosis. Next, we tested whether or not the ERO1L gene is involved in progression to metastatic disease in gastric cancer,especially in late tumorigenesis, including migration and invasion. As a results, Knock down expression for ERO1L significantly decreased the migration and invasiveness of gastric cancer cells. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers in. in vivo, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer.
Citation Format: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho. Expression of ERO1L gene is poor prognostic factor for gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1147. doi:10.1158/1538-7445.AM2013-1147
Abstract 1151: Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis.
Authors: Goos Jeroen A C M , Coupé Veerle M H , Diosdado Begoña , Delis-van Diemen Pien M. , Karga Cemile , Beliën Jeroen A.M. , Carvalho Beatriz , van den Tol M. Petrousjka , Verheul Henk M W , Geldof Albert A. , Meijer Gerrit A. , Hoekstra Otto S. , Fijneman Remond J A 
Published: August 2014

Abstract
Introduction: Approximately half of all colorectal cancer (CRC) patients die as a consequence of metastases. Hemihepatectomy, occasionally in combination with radiofrequency ablation (RFA), is the only curative treatment available for patients with CRC liver metastases (CRCLM). Patient eligibility is based on established prognostic clinicopathological variables, however, 70% of patients still die within 5 years indicating that better prognostic markers are needed. Aurora kinase A (AURKA) is a driver of 20q gain-associated tumor progression and is associated with disease recurrence in stage III CRC patients. AIM: This study aimed to investigate the prognostic value of AURKA protein expression in liver metastases of CRC patients who underwent hemihepatectomy with curative intent. Patients and Methods: Tissue microarrays (TMAs) were generated from formalin-fixed paraffin-embedded CRCLM of 507 patients who underwent hemihepatectomy in the Netherlands between 1990 and 2010. Matched primary CRC tissue was collected of 234 patients. TMAs were stained for AURKA by immunohistochemistry, nuclear expression of neoplastic cells was assessed and subsequently associated with patient overall survival (OS) in a training and validation set. Results: High AURKA expression in CRCLM was associated with poor OS in a univariate analysis (HRR 1.68; 95%CI 1.04-2.73; P=0.03) and upon correction for established prognostic clinicopathological variables (HRR 1.77; 95%CI 1.02-3.08; P=0.04). Furthermore, AURKA expression in liver metastases was correlated to its expression in corresponding primary CRC (P=0.0002). Conclusion and Discussion: AURKA protein expression is a molecular biomarker with prognostic value for CRC patients with liver metastasis, independent of established clinicopathological variables. This study opens novel opportunities to investigate AURKA inhibitors for personalized therapy.
Citation Format: Jeroen A C M Goos, Veerle M H Coupé, Begoña Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, Beatriz Carvalho, M. Petrousjka van den Tol, Henk M W Verheul, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J A Fijneman. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1151. doi:10.1158/1538-7445.AM2013-1151
Abstract 1154: Detection of aberrant methylation of the RASSF1A gene as a biomarker for hepatocellular carcinoma.
Authors: Jain Surbhi , Xie Lijia , Boldbaatar Batbold , Su Ying-Hsiu , Song Wei 
Published: August 2014

Abstract
Hepatocellular carcinoma (HCC) is an aggressive malignancy that is responsible for between 250,000 and 800,000 deaths annually worldwide. HCC has a poor prognosis with a 5-year survival rate of less than 15% mainly due to a lack of early detection. The current biomarker for HCC is the alpha-fetoprotein (AFP), which has a low sensitivity of 40-60%. There is a necessity for non-invasive, convenient, and sensitive methods to detect the cancer in its curative stages to improve prognosis. Previous studies from our laboratory showed that the location of the CpG site methylation studied could impact the marker performance in distinguishing HCC from other liver diseases. The aberrant methylation of the tumor-suppressor RASSF1A gene has been extensively studied as a marker for a variety of cancers, including liver cancer. However, some studies found that the gene was methylated even in non-cancerous liver tissues. Thus, in order to explore the possibility of detecting aberrant methylation of the tumor-suppressor RASSF1A gene as a biomarker for HCC screening, we analyzed the methylation profiles of 57 CpG sites in three regions of the promoter - P1, P2, and E1 - in normal, hepatitic, cirrhotic, adjacent non-HCC, and HCC tissue samples through bisulfite DNA sequencing. We discovered that the P1 region was most specifically methylated to HCC. We then confirmed the findings by developing a methylation specific PCR and analyzing a larger sample size. The data were analyzed and the P1 test was found to have an area under the curve (AUROC) of 0.90, whereas the E1 and P2 tests had AUROC of 0.84 and 0.72, respectively. At a cutoff of 10 copies for our analysis, the P1 MSP gave a sensitivity of 80.8% and specificity of 85.7%. Furthermore, we found that out of 62 AFP-negative samples, mRASSF1A detected 54 (87.1%). By combining AFP and mRASSF1A, 107 of 115 (93.0%) of HCC samples were detected as cancerous. Subsequently, we developed a PCR assay to detect the methylated RASSF1A gene in the urine of patients. This assay was then used to test the urine DNA isolated from patients with hepatitic, cirrhotic, or HCC after which the data were statistically evaluated. The potential of a urine DNA test for HCC screening is discussed.
Citation Format: Surbhi Jain, Lijia Xie, Batbold Boldbaatar, Ying-Hsiu Su, Wei Song. Detection of aberrant methylation of the RASSF1A gene as a biomarker for hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1154. doi:10.1158/1538-7445.AM2013-1154
Abstract 1155: Promoter CpG island hypermethylation of Decoy Receptor 1 (DCR1) is associated with poor response to irinotecan in colorectal cancer.
Authors: Bosch Linda JW , Trooskens Geert , Snaebjornsson Petur , Haan Josien C. , Pelosof Lorraine , Koopman Miriam , Tol Jolien , Louwagie Joost , Dehaspe Luc , Ylstra Bauke , Verheul Henk , van Engeland Manon , Nagtegaal Iris D. , Herman James G. , Punt Cornelis JA , van Criekinge Wim , Carvalho Beatriz , Meijer Gerrit A. 
Published: August 2014

Abstract
Background
Heterogeneity in the biology of colorectal cancer (CRC) is associated with variable responses to standard chemotherapy. We aimed to identify DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of patients with metastatic CRC.
Material and Methods
The presence of DNA methylation for a selected panel of 22 genes was assessed by methylation specific PCR (MSP) on primary tumors of 185 patients with metastatic CRC treated with first-line capecitabine (CAP, n=90) or a combination of capecitabine and irinotecan (CAPIRI, n=95) in the phase III CAIRO trial. Methylation status of each gene was correlated to progression free survival (PFS) by treatment regimen. Genes for which methylation status associated with response to irinotecan, were validated in 166 patients treated with first-line CAP (n=78) or CAPIRI (n=88).
Results
Decoy Receptor 1 (DCR1) was identified as a novel hypermethylated gene in CRC. In CAPIRI treated patients, DCR1 methylation was correlated to a shorter PFS compared to patients with unmethylated DCR1 (hazard ratio [HR]=0.4 (95%CI =0.3-0.7), p = 0.0009). In patients with methylated DCR1 PFS did not improve with CAPIRI treatment, compared to treatment with CAP (discovery set: HR=0.8 (95%CI=0.5-1.3, p=0.4); validation set: HR=1.1 (95%CI 0.7-1.7, p=0.6)), in contrast to patients with unmethylated DCR1 (discovery set: HR=2.5 (95%CI 1.7-3.3, p=0.00004); validation set: HR=1.7 (95%CI 1.1-2.0, p=0.004)).
Conclusion
CRC patients with methylated DCR1 did not benefit from adding irinotecan to capecitabine therapy, indicating that DCR1 methylation status may guide selecting metastatic CRC patients for irinotecan-based therapy.
Citation Format: Linda JW Bosch, Geert Trooskens, Petur Snaebjornsson, Josien C. Haan, Lorraine Pelosof, Miriam Koopman, Jolien Tol, Joost Louwagie, Luc Dehaspe, Bauke Ylstra, Henk Verheul, Manon van Engeland, Iris D. Nagtegaal, James G. Herman, Cornelis JA Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A. Meijer. Promoter CpG island hypermethylation of Decoy Receptor 1 (DCR1) is associated with poor response to irinotecan in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1155. doi:10.1158/1538-7445.AM2013-1155
Abstract 1159: Increased ceramide synthase 5 expression is associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer.
Authors: Fitzgerald Seán , Sheehan Katherine M. , O'Grady Anthony , Kenny Dermot , O'Kennedy Richard , Kay Elaine W. , Kijanka Gregor 
Published: August 2014

Abstract
Background: Ceramide synthase 5 (CerS5) is multi-pass transmembrane protein of the endoplasmic reticulum. Functioning as a bona fide (dihydro)ceramide synthase, CerS5 regulates the levels of short ceramide species. Ceramides are bioactive lipids implicated in proliferation, senescence, angiogenesis and death of normal and cancerous cells. We aimed to investigate CerS5 expression in colorectal cancer tissue and to evaluate the prognostic significance of CerS5 in colorectal cancer patients.
Methods: CerS5 expression was analyzed by immunohistochemistry on tissue microarrays constructed from 125 colorectal cancer patients. The associations between CerS5 staining and the clinicopathological factors were examined using the Spearman rank correlation test. Patient survival was examined using the Kaplan-Meier survival analysis and Cox proportional hazard modeling, categorized according to high or low CerS5 staining intensity.
Results: Immunohistological staining revealed an overexpression of membranous CerS5 in 63 out of 125 (50.4%) colorectal carcinomas. CerS5 overexpression significantly correlated with lymphovascular invasion and metastatic disease in matched tumor cases (P = 0.036 & P = 0.037, respectively). Patients with CerS5 overexpressing tumors had a significantly lower overall 5-year survival (OS, P = 0.029) and 5-year recurrence-free survival (RFS, P = 0.047). Cox multivariate analysis showed that the increased CerS5 expression was an independent predictor of OS (hazard ratio (HR) = 1.604; 95% confidence interval (CI) 1.010-2.548, P = 0.045) and RFS (HR = 1.592; CI 1.036-2.447, P = 0.034).
Conclusions: We found an increased expression of ceramide synthase 5 (CerS5) in 50% of investigated colorectal carcinomas, which was associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer patients. Our study identifies CerS5 as a novel independent prognostic biomarker for patients with colorectal cancer.
Citation Format: Seán Fitzgerald, Katherine M. Sheehan, Anthony O'Grady, Dermot Kenny, Richard O'Kennedy, Elaine W. Kay, Gregor Kijanka. Increased ceramide synthase 5 expression is associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1159. doi:10.1158/1538-7445.AM2013-1159
Abstract 1160: Inactivated hippo-pathway as a prognostic biomarker in hepatocellular carcinoma.
Authors: Hayashi Hiromitsu , Kuroki Hideyuki , Yokoyama Naomi , Nakagawa Shigeki , Nitta Hidetoshi , Imai Katsunori , Hashimoto Daisuke , Ikuta Yoshiaki , Chikamoto Akira , Beppu Toru , Baba Hideo 
Published: August 2014

Abstract
The contact inhibition of proliferation and cell movement is crucially important in embryonic development, tissue regeneration, and wound healing for the well-controlled organogenesis. The disruption of contact inhibition results in sustained cell proliferation and uncontrolled cell movement, which is a hallmark of solid tumors. Loss of contact inhibition allows cancer cells to facilitate the invasion of neighboring tissues and metastasis to remote organs. The recently identified Hippo signaling pathway has been implicated in contact inhibition of proliferation as well as organ size control. Indeed, the conditional inactivation of hippo-pathway in liver leads to enlarged liver (massive hepatomegaly) and tumorigenesis (Cell, 2007). Clinically, HCC often shows the huge tumor more than size in 10cm, strongly speculating that inactivation of hippo-pathway plays an important role in HCC progression. However, clinical significance of hippo-pathway in HCC is largely unknown. Here, we investigated the clinical significance of inactivated hippo-pathway, which induce overexpressed oncogenes (YAP/TAZ), using resected 80 HCC samples, and suggested the tumoral-high TAZmRNA expression was a worse prognostic biomarker for HCC patients represented by high proliferative activity. The tumor size in High TAZmRNA expression group (n =24) was significantly larger than that in low expression group (n = 56) (P &lt; 0.05). YAP/TAZ protein over-expression in HCC was associated with high proliferative activity by Ki-67 positive cells. The high TAZmRNA expression group showed significantly worsen disease free survival and overall survival compared with that in low expression group (P = 0.01 and 0.02, respectively). Thus, inactivation of Hippo-pathway plays a crucial role in tumor progression by accelerating proliferative activity, and tumoral TAZmRNA expression level may be a useful prognostic biomarker in HCC.
Citation Format: Hiromitsu Hayashi, Hideyuki Kuroki, Naomi Yokoyama, Shigeki Nakagawa, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Yoshiaki Ikuta, Akira Chikamoto, Toru Beppu, Hideo Baba. Inactivated hippo-pathway as a prognostic biomarker in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1160. doi:10.1158/1538-7445.AM2013-1160
Abstract 1168: Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis .
Authors: Cho Dong-Hyung , Jo Yoon Kyung , Kim Seung Cheol , Park In Ja , Kim Jin Cheon 
Published: August 2014

Abstract
Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown. To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line - 8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p=0.005) and invasion (p&lt;0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p=0.012). Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.
Citation Format: Dong-Hyung Cho, Yoon Kyung Jo, Seung Cheol Kim, In Ja Park, Jin Cheon Kim. Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1168. doi:10.1158/1538-7445.AM2013-1168