| 1. |
Shotaro Sakimura 1 2 , Satoshi Nagayama 3 , Mitsuko Fukunaga 1 , Qingjiang Hu 1 , Akihiro Kitagawa 1 , Yuta Kobayashi 1 , Takanori Hasegawa 4 , Miwa Noda 1 , Yuta Kouyama 1 , Dai Shimizu 1 , Tomoko Saito 1 , Atsushi Niida 5 , Yusuke Tsuruda 1 , Hajime Otsu 1 , Yoshihiro Matsumoto 1 , Hiroki Uchida 1 , Takaaki Masuda 1 , Keishi Sugimachi 1 , Shin Sasaki 6 , Kazutaka Yamada 7 , Kazuki Takahashi 8 , Hideki Innan 8 , Yutaka Suzuki 9 , Hiromi Nakamura 10 , Yasushi Totoki 10 , Shinichi Mizuno 11 , Masanobu Ohshima 12 , Tatsuhiro Shibata 10 13 , Koshi Mimori 1, Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases, PLoS Genet., 10.1371/journal.pgen.1009113., 17, 1, e1009113, 2021.01, A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.. |
| 2. |
Shotaro Sakimura 1 2 , Keishi Sugimachi 1 , Junji Kurashige 1 , Masami Ueda 1 , Hidenari Hirata 1 , Sho Nambara 1 , Hisateru Komatsu 1 , Tomoko Saito 1 , Yuki Takano 1 , Ryutaro Uchi 1 , Etsuko Sakimura 1 , Yoshiaki Shinden 1 , Tomohiro Iguchi 1 , Hidetoshi Eguchi 1 , Yugo Oba 2 , Sumio Hoka 2 , Koshi Mimori 3, The miR-506-Induced Epithelial-Mesenchymal Transition is Involved in Poor Prognosis for Patients with Gastric Cancer, Ann Surg Oncol., 10.1245/s10434-015-4418-2., Suppl 3, 1436-1443, 2015.12, Background: MicroRNAs have roles in the regulation of the epithelial-mesenchymal transition (EMT). Findings have shown that miR-506 inhibits the expression of SNAI2 and that low expression of miR-506 is associated with poor prognoses in ovarian and breast cancers. This study investigated the role of miR-506 in survival and the EMT in patients with gastric cancer.
Methods: In this study, miR-506 and SNAI2 mRNA levels were measured in 141 cases of gastric cancer by quantitative reverse transcription polymerase chain reaction, and the protein expressions of SNAI2 and E-cadherin in 39 cases were validated by immunohistochemical analysis. Next, the associations between their expression levels and clinicopathologic factors were evaluated. In addition, cell proliferation, migration, and luciferase activity of the 3' untranslated region (UTR) of SNAI2 were analyzed using pre-miR-506 precursor in two human gastric cancer cell lines.
Results: Low expression of miR-506 was significantly correlated with poor overall survival in both the univariate analysis (P = 0.016) and the multivariate analysis (P |
