OBJECTIVE: Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells (CTCs) correlated with therapeutic efficacy for advanced gastric cancer (AGC) patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients' clinical prognosis. METHODS: The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment (SE) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy. RESULTS: CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 mL and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival (PFS) and overall survival (OS). In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS. CONCLUSIONS: Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
OBJECTIVE: Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells (CTCs) correlated with therapeutic efficacy for advanced gastric cancer (AGC) patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients' clinical prognosis. METHODS: The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment (SE) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy. RESULTS: CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 mL and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival (PFS) and overall survival (OS). In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS. CONCLUSIONS:Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.
Authors: David T Miyamoto; Yu Zheng; Ben S Wittner; Richard J Lee; Huili Zhu; Katherine T Broderick; Rushil Desai; Douglas B Fox; Brian W Brannigan; Julie Trautwein; Kshitij S Arora; Niyati Desai; Douglas M Dahl; Lecia V Sequist; Matthew R Smith; Ravi Kapur; Chin-Lee Wu; Toshi Shioda; Sridhar Ramaswamy; David T Ting; Mehmet Toner; Shyamala Maheswaran; Daniel A Haber Journal: Science Date: 2015-09-18 Impact factor: 47.728
Authors: Phung Thanh Huong; Sanjeev Gurshaney; Nguyen Thanh Binh; Anh Gia Pham; Huy Hoang Nguyen; Xuan Thanh Nguyen; Hai Pham-The; Phuong-Thao Tran; Khanh Truong Vu; Nhuong Xuan Duong; Claudio Pelucchi; Carlo La Vecchia; Paolo Boffetta; Hung D Nguyen; Hung N Luu Journal: Cancers (Basel) Date: 2020-03-15 Impact factor: 6.639