- Email: [email protected]
OP0016 Development of a panel of five miRNAs as a diagnostic tool for non-small-cell lung cancer
Abstracts / 51 (2015) e1–e36
of the FAS variant genotype was only significant among participants of Malay ethnicity (OR 5.377, 95% CI 2.085–13.865, p = 0.001), whereas significance of the MDM2 polymorphism was not observed in all ethnic groups. When stratified by patient HPV type, the association of the FAS polymorphism remained significant only in cervical cancers mediated by HPV16 (OR 3.333, 95% CI 1.127–9.863, p = 0.030) and ‘other’ HPV types (OR 6.00, 95% CI 1.565–23.007, p = 0.009), whereas MDM2 polymorphism remained significant only in HPV16-mediated cancer (OR 4.740, 95% CI 1.525–14.729, p = 0.007). Significant associations were also observed for various FAS-p53 and FAS-MDM2, but not p53-MDM2, combination genotypes. Interpretation: FAS 670A>G and MDM2 309T>G polymorphisms could play a role in modulating cervical cancer risk among Malaysian women. This study is being continued with a larger sample size.
http://dx.doi.org/10.1016/j.ejca.2015.06.016
OP0016 DEVELOPMENT OF A PANEL OF FIVE MIRNAS AS A DIAGNOSTIC TOOL FOR NON-SMALL-CELL LUNG CANCER Chun-Ni Zhang *, Cheng Wang, Meng Ding, Ming-De Xia, Si-Di Chen, Anh Van Le, Rafael Soto-Gil, Yi Shen, Jun-Jun Wang, Nan Wang, Wan-Jian Gu, Xiang-Dong Wang, Yan-Ni Zhang, Ke Zen, Xi Chen, Chen-Yu Zhang. Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, China, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China, Department of Thoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China, Johnson & Johnson Innovation Center Asia Pacific, Shanghai, China, Ortho-Clinical Diagnostics, NL, USA, Department of Clinical Laboratory, Jiangsu Province Hospital of TCM, China, Department of Clinical Laboratory, Nanjing Chest Hospital, Nanjing, China, Department of Medical Oncology, Cancer Hospital of Xuzhou, Xuzhou, China Background: Circulating miRNAs have been recognised as stable markers for cancer detection. However, multiethnic, double-blind studies of non-small-cell lung cancer (NSCLC) are lacking. We aimed to identify a panel of serum miRNAs capable of accurately diagnosing NSCLC in ethnically diverse patients. Methods: We randomly assigned 438 participants from both China and America, including 221 NSCLC patients, 160 normal controls, and 57 benign nodules. An initial miRNA screening was done on two pooled serum samples respectively from NSCLC and normal controls from a Chinese cohort using the TaqMan Low-Density Array. Candidate miRNAs from the screen were validated by qRT-PCR analysis in two additional Chinese cohorts. Risk score analysis was done to evaluate the diagnostic value of the selected miRNAs. Finally, we did a double-blind trial on 212 samples from an American cohort to validate our findings. Findings: In both the training and validation sets, qRT-PCR analysis confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214, and miR-7 were significantly increased in Chinese patients with NSCLC compared with those in normal controls. The AUCs of the ROC curve of this five serum miRNA panel were 0.976 and 0.823 for the two confirmation sets, respectively. Furthermore, in a double-blind trial, the miRNA panel correctly classified 95% NSCLC cases and 84% normal and benign nodules controls. In addition, the panel was capable of distinguishing
e5
NSCLC from benign nodules with an AUC of 0.979 and sensitivity and specificity of 95% in the American cohort. The panel allowed correct prediction of 11 of 13 (85%) stage I–II tumours in Chinese cohorts and 55 of 58 (95%) stage I–II tumours in American cohort. Interpretation: A panel of five serum miRNAs holds potential for accurate diagnosis of NSCLC in patients of different ethnicity.
http://dx.doi.org/10.1016/j.ejca.2015.06.017
P0005 LOW TESTOSTERONE LEVELS AND INCREASED SERUM C REACTIVE PROTEIN LEVELS IN CANCER PATIENTS WITH REFRACTORY CACHEXIA H. Engin *, C. Bilir. Department of Medical Oncology, Bu¨lent Ecevit University, Zonguldak, Turkey Background: Cachexia has long been recognised as an adverse effect of cancer. Cancer cachexia (CC) has three stages of clinical relevance: precachexia, cachexia, and refractory cachexia (RC). Methods: This study includes 36 patients diagnosed with CC (of whom 17 patients had RC and remaining 19 had cachexia) at the Department of Medical Oncology, Bu¨lent Ecevit University, and 24 healthy controls, who enrolled between May 2011, and February 2013. Findings: We investigated the levels of serum C reactive protein (CRP), IL-1 alfa, IL-1 beta, TNF alfa, and free and total testosterone in male patients with CC. In the group of men with refractory cachexia, serum CRP levels were significantly higher (139 mg/l versus 3.8 mg/l, p = 0.0001) and serum testosterone levels were significantly lower (170 ng/dl versus 450 ng/dl, p = 0.0001) than in the cachexia group. There were no significant differences in the serum levels of IL1 alfa, IL1 beta, TNF alfa, and serum free testosterone levels. Interpretation: In RC, there has been a clinically refractory process as a result of end-stage disease. Our study revealed that CRP levels increase and testosterone levels decrease in refractory cachexia. In a pre-cachectic or cachectic patient, basal CRP levels can be followed up and increasing CRP levels and/or decreasing testosterone levels must alert to proceeding to irreversible catabolism, such as RC.
http://dx.doi.org/10.1016/j.ejca.2015.06.018
P0007 HIGH-GRADE T1 BLADDER UROTHELIAL CARCINOMA: OPTIMAL MANAGEMENT Anmar Nassir. King Abdullah Medical City, Makkah, Saudi Arabia Objective: I aimed to investigate the best options for patients with high-grade T1 bladder cancer. Methods: Between 2006 and 2011, 39 patients were diagnosed with high-grade T1 bladder cancer at the King Abdullah Medical City, Makkah, Saudi Arabia. Average follow-up was 60 months. Multifocal tumours larger than 2 cm were found in 36 (92%) patients. Carcinoma in situ was found in four (10.3%) patients. Residual disease was found in 15 (38.5%) patients. Findings: Seven patients underwent early radical cystectomy and bladder reconstruction (neo-bladder). The remaining 32 patients were treated with intravesical Bacillus Calmette-Gue´rin (BCG) therapy, except for one patient, who received gemcitabine. During follow-up,
of the FAS variant genotype was only significant among participants of Malay ethnicity (OR 5.377, 95% CI 2.085–13.865, p = 0.001), whereas significance of the MDM2 polymorphism was not observed in all ethnic groups. When stratified by patient HPV type, the association of the FAS polymorphism remained significant only in cervical cancers mediated by HPV16 (OR 3.333, 95% CI 1.127–9.863, p = 0.030) and ‘other’ HPV types (OR 6.00, 95% CI 1.565–23.007, p = 0.009), whereas MDM2 polymorphism remained significant only in HPV16-mediated cancer (OR 4.740, 95% CI 1.525–14.729, p = 0.007). Significant associations were also observed for various FAS-p53 and FAS-MDM2, but not p53-MDM2, combination genotypes. Interpretation: FAS 670A>G and MDM2 309T>G polymorphisms could play a role in modulating cervical cancer risk among Malaysian women. This study is being continued with a larger sample size.
http://dx.doi.org/10.1016/j.ejca.2015.06.016
OP0016 DEVELOPMENT OF A PANEL OF FIVE MIRNAS AS A DIAGNOSTIC TOOL FOR NON-SMALL-CELL LUNG CANCER Chun-Ni Zhang *, Cheng Wang, Meng Ding, Ming-De Xia, Si-Di Chen, Anh Van Le, Rafael Soto-Gil, Yi Shen, Jun-Jun Wang, Nan Wang, Wan-Jian Gu, Xiang-Dong Wang, Yan-Ni Zhang, Ke Zen, Xi Chen, Chen-Yu Zhang. Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, China, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, China, Department of Thoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China, Johnson & Johnson Innovation Center Asia Pacific, Shanghai, China, Ortho-Clinical Diagnostics, NL, USA, Department of Clinical Laboratory, Jiangsu Province Hospital of TCM, China, Department of Clinical Laboratory, Nanjing Chest Hospital, Nanjing, China, Department of Medical Oncology, Cancer Hospital of Xuzhou, Xuzhou, China Background: Circulating miRNAs have been recognised as stable markers for cancer detection. However, multiethnic, double-blind studies of non-small-cell lung cancer (NSCLC) are lacking. We aimed to identify a panel of serum miRNAs capable of accurately diagnosing NSCLC in ethnically diverse patients. Methods: We randomly assigned 438 participants from both China and America, including 221 NSCLC patients, 160 normal controls, and 57 benign nodules. An initial miRNA screening was done on two pooled serum samples respectively from NSCLC and normal controls from a Chinese cohort using the TaqMan Low-Density Array. Candidate miRNAs from the screen were validated by qRT-PCR analysis in two additional Chinese cohorts. Risk score analysis was done to evaluate the diagnostic value of the selected miRNAs. Finally, we did a double-blind trial on 212 samples from an American cohort to validate our findings. Findings: In both the training and validation sets, qRT-PCR analysis confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214, and miR-7 were significantly increased in Chinese patients with NSCLC compared with those in normal controls. The AUCs of the ROC curve of this five serum miRNA panel were 0.976 and 0.823 for the two confirmation sets, respectively. Furthermore, in a double-blind trial, the miRNA panel correctly classified 95% NSCLC cases and 84% normal and benign nodules controls. In addition, the panel was capable of distinguishing
e5
NSCLC from benign nodules with an AUC of 0.979 and sensitivity and specificity of 95% in the American cohort. The panel allowed correct prediction of 11 of 13 (85%) stage I–II tumours in Chinese cohorts and 55 of 58 (95%) stage I–II tumours in American cohort. Interpretation: A panel of five serum miRNAs holds potential for accurate diagnosis of NSCLC in patients of different ethnicity.
http://dx.doi.org/10.1016/j.ejca.2015.06.017
P0005 LOW TESTOSTERONE LEVELS AND INCREASED SERUM C REACTIVE PROTEIN LEVELS IN CANCER PATIENTS WITH REFRACTORY CACHEXIA H. Engin *, C. Bilir. Department of Medical Oncology, Bu¨lent Ecevit University, Zonguldak, Turkey Background: Cachexia has long been recognised as an adverse effect of cancer. Cancer cachexia (CC) has three stages of clinical relevance: precachexia, cachexia, and refractory cachexia (RC). Methods: This study includes 36 patients diagnosed with CC (of whom 17 patients had RC and remaining 19 had cachexia) at the Department of Medical Oncology, Bu¨lent Ecevit University, and 24 healthy controls, who enrolled between May 2011, and February 2013. Findings: We investigated the levels of serum C reactive protein (CRP), IL-1 alfa, IL-1 beta, TNF alfa, and free and total testosterone in male patients with CC. In the group of men with refractory cachexia, serum CRP levels were significantly higher (139 mg/l versus 3.8 mg/l, p = 0.0001) and serum testosterone levels were significantly lower (170 ng/dl versus 450 ng/dl, p = 0.0001) than in the cachexia group. There were no significant differences in the serum levels of IL1 alfa, IL1 beta, TNF alfa, and serum free testosterone levels. Interpretation: In RC, there has been a clinically refractory process as a result of end-stage disease. Our study revealed that CRP levels increase and testosterone levels decrease in refractory cachexia. In a pre-cachectic or cachectic patient, basal CRP levels can be followed up and increasing CRP levels and/or decreasing testosterone levels must alert to proceeding to irreversible catabolism, such as RC.
http://dx.doi.org/10.1016/j.ejca.2015.06.018
P0007 HIGH-GRADE T1 BLADDER UROTHELIAL CARCINOMA: OPTIMAL MANAGEMENT Anmar Nassir. King Abdullah Medical City, Makkah, Saudi Arabia Objective: I aimed to investigate the best options for patients with high-grade T1 bladder cancer. Methods: Between 2006 and 2011, 39 patients were diagnosed with high-grade T1 bladder cancer at the King Abdullah Medical City, Makkah, Saudi Arabia. Average follow-up was 60 months. Multifocal tumours larger than 2 cm were found in 36 (92%) patients. Carcinoma in situ was found in four (10.3%) patients. Residual disease was found in 15 (38.5%) patients. Findings: Seven patients underwent early radical cystectomy and bladder reconstruction (neo-bladder). The remaining 32 patients were treated with intravesical Bacillus Calmette-Gue´rin (BCG) therapy, except for one patient, who received gemcitabine. During follow-up,