Human Cytomegalovirus US28 Gene in Colorectal Cancer and Its Association with Clinical Outcomes

• Main Authors: Yu Chiang, 江宇
• Other Authors: Yu-Jiun Chan
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/76a5ae

碩士 === 國立陽明大學 === 公共衛生研究所 === 107 === The human cytomegalovirus (HCMV) US28 transmembrane protein, a G protein coupled recrptor (GPCR) is genetically variable in clinical isolates. The protein is associated with cell proliferation. Previous study was focused on samples from immunocompromised patients or congenital infected fetus. This study focused on clinical isolates and samples form colorectal cancer patients from a tertiary hospital. Sixty-nine HCMV clinical isolates was colleted from Taipei Veterans General Hospital (TVGH) during 2018. Tumor samples were obtained from 200 colorectal cancer patients from Biobank of Residual Surgical Tissues at the Division of Colorectal Surgery ,TVGH. A primer pair, covering the HCMV whole US28 gene (seq. 1-1062), was redesigned to detect the region. Combining polymerase chain reaction (PCR) and sequencing, the HCMV US28 gene in CRC samples was determined. Mixed HCMV genes in one sample were resolved by cloning and re-sequencing. The nucleotide sequences were aligned and edited using BioEdit. Phylogenetic analysis was conducted using MEGA X. Neighbor-joining tree was used to reconstruct a tree with 1000 bootstrap. Bootstrap values ≧70% were considered definitive for significant clustering. The clinical, pathological and survival data were analyzed amongst tumors with different US28 groups. We used the Kaplan-Meier method to estimate patients’ survival. Significant differences in the survival curves were evaluated with a Mantel-Cox log-rank test. HCMV US28 genes were detected in 77 of 200 tumor specimens (38.5 %). According to the sequencing data, five major groups (alpha to epsilon) were identified. There were 65 single group and 12 mixed-groups. For all the samples with sequencing data, there were 34 alpha (44.2%), 7 beta (9%), 6 gamma (7.8%), 16 delta (20.5%) and 2 epsilon (2.6%). Amongst the stage I, II, and III CRC patients (n=160) those who contained US28 gamma type revealed worse disease-free survival (DFS) than others (p=0.018).