Background: Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free sera, plasma and other bodily fluids of healthy subjects and cancer patients. We have previously demonstrated that human serum or plasma contains microRNAs (miRNAs) and long non-coding RNA (lncRNAs) that are significantly up-regulated or down-regulated in various types of cancer and are of good diagnostic value for screening. The mechanisms underlying the stability of serum RNAs are unclear; lncRNAs may be protected by extracellular vesicles (EV) including apoptotic body (AB), microvesicle (MV) and exosome (EXO), as for circulating miRNAs. In order to find optimal method to evaluate the potential utility of circulating lncRNAs for cancer diagnosis or prognosis, more exploration should be undertook for the distribution of circulating lncRNAs. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In serous vesicles of both colorectal cancer and healthy subjects, 17 of the 39 cancer-related lncRNAs were detected, including TDRG1, MEG3, DSCAM-AS1, 7SK, MIR31HG, CBR3-AS1, TUG1, BCAR4, EPB41L4A, PCA3, FAS-AS1, SUMO1P3, uc338, PRNCR1, PTENP1 and CUDR. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In sera of both colorectal cancer and healthy subjects, 16 out of the 39 cancer-related lncRNAs were detected. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Conclusions: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured lncRNAs, while the MVs contained the least amount of lncRNAs. EXOs, as their intercellular origin, have reasons to contain higher amount of lncRNAs among serous vesicles and seem to be the most promising research materials in the field of circulating lncRNA. Citation Format: Dong Lei, Lin Wanrun, Qi Peng, Xu Midie, Du Xiang. Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B38.
Introduction: Conflicting reports exist regarding characteristics and outcomes of patients with only invasive lobular carcinoma (ILC) and mixed invasive lobular and ductal carcinoma (ILC/IDC). The purpose of this project is to report experience of 20 year cohort at one institution. Methods: Patients diagnosed with ILC between 1990 and 2010 were divided into two groups: ILC alone and ILC/IDC. Patient demographics, history, diagnosis and treatment modalities, and outcomes were captured. Chi-square, log-rank, and Wilcoxon rank sums tests were utilized for statistical analysis. P < 0.05 was considered significant. Results: In 189 AJCC Stage I-III patients, ILC was identified in 149 (79%) and ILC/IDC in 39 (21%). ILC stage was I, II, III in 46 (31%), 57 (41%), 32 (21%) ILC, and ILC/IDC was 17 (44%), 16 (41%), 4 (10%). Median age (range) at diagnosis was 64 (31-88) for ILC and 64 (35-84) years for ILC/IDC (p = 0.78). Median largest tumor diameter was 22 (range 1-100) in ILC, and 20 (range 2-110) mm in ILC/IDC (p = 0.97). Seventy-eight (52%) and 20 (51%) were diagnosed with ILC and ILC/IDC clinically, and 58 (39%) and 15 (38%) were diagnosed with ILC and ILC/IDC radiographically (p = 0.96). Treatment modalities were mastectomy and breast conservation therapy in 82(55%) and 67(45%) of patients with ILC, 18 (46%) and 21 (54%) of patients with ILC/IDC (p = 0.32). In 136 (91%) ILC and 33 (85%) ILC/IDC patients who had nodal evaluation/excision, 59 (43%) ILC and 12 (36%) ILC/IDC patients presented with positive nodal status. ER, PR, and HER2 status were positive in 132 (89%), 104 (70%), 7 (5%) ILC, and 29 (74%), 26 (67%), 3 (8%) ILC/IDC patients respectively (p = 0.02, p = 0.85, p = 0.17). Median (range) follow-up for ILC was 6.1 (< 1-22.3), and 8.0 (1.72-17.7) years for ILC/IDC (p = 0.03). At the time of analysis, 43(29%) patients with ILC, and 11(28%) patients with ILC/IDC had expired (p = 0.94). Median (range) follow-up for patients who were alive at time of analysis was 6.8 (<1-20.7) years for ILC, and10.1 (2.3-17.7) years for ILC/IDC (p = 0.06). Time to first recurrence was 3.23 (0.8-17.0) years in ILC, and 5.2 (2.9-9.3) years in ILC/IDC (p = 0.20). Recurrence was identified in 33(22%) ILC: 15(46%) locoregional and18 (54%) distant disease. Similarly, recurrence was found in 7 (20%) ILC/IDC patients: 4 locoregional and 3 distant. Most locoregional recurrences, 12/15 (80%), occurred in the ipsilateral breast in ILC, and 3/4 (75%) in ILC/IDC (p = 0.82). Five years disease free survival rates were 76% ILC and 85% for ILC/IDC, and 10 years rates were 63% for ILC and 67% for ILC/IDC (p = 0.4941). Overall survival estimates at 5 years were 84% for ILC and 92% for ILC/IDC, and at 10 years were 65% for ILC and 74% for ILC/IDC (p = 0.52). Conclusion: While basic demographics and survival patterns did not differ statistically between ILC and ILC/IDC, pure ILC histology tends to carry a higher risk of recurrence, as well as worse disease free and overall survival compared to ILC/IDC. ILC histology was more likely to be ER positive, present with advanced stage, and recur in the ipsilateral breast than the contralateral breast. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-35.
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