Department of Pathology, Jining No. 1 People's Hospital, Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, 272111, Shandong, China.
Department of Oncology, Jining No. 1 People's Hospital, Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, Jining, 272111, Shandong, China.
Hum Cell. 2020 Jan;33(1):116-122. doi: 10.1007/s13577-019-00280-2. Epub 2019 Sep 24.
Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a newly identified member of B7 family; HHLA2 protein expression has been suggested to be increased levels in many kinds of human cancers. However, HHLA2 protein expression in gastric cancer tissues and its clinical significance are still unknown. The purpose of this study was to investigate the HHLA2 protein expression pattern in gastric cancer tissues and the correlation between HHLA2 protein expression and clinicopathological characteristics including clinical outcome in gastric cancer patients. In our results, we observed HHLA2 expression was increased in gastric cancer tissue specimens compared with normal stomach tissue specimens through analyzing HHLA2 expression data from 408 gastric cancer tissue specimens and 211 normal stomach tissue specimens at databases. Furthermore, we, respectively, performed quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry to verify HHLA2 mRNA and protein expressions in gastric cancer tissues and normal stomach tissues, and found HHLA2 mRNA and protein expressions were up-regulated in gastric cancer tissues. Moreover, we found high HHLA2 expression was correlated with advanced clinical stage, deep tumor invasion, lymph node metastasis, distant metastasis and short overall survival in gastric cancer. The multivariable Cox's proportional hazard models indicated high HHLA2 expression was a poor independent prognostic factor for overall survival in patients with gastric cancer. In conclusion, HHLA2 protein overexpression in gastric cancer tissue is potential risk factor for malignant status and poor prognosis.
人类内源性逆转录病毒-H 长末端重复相关蛋白 2（HHLA2）是 B7 家族的新成员；已有研究表明 HHLA2 蛋白在许多人类癌症中表达水平升高。然而，胃癌组织中 HHLA2 蛋白的表达及其临床意义尚不清楚。本研究旨在探讨 HHLA2 蛋白在胃癌组织中的表达模式及其与胃癌患者临床病理特征（包括临床结局）的相关性。通过分析 408 例胃癌组织标本和 211 例正常胃组织标本数据库中 HHLA2 表达数据，我们观察到 HHLA2 在胃癌组织标本中的表达高于正常胃组织标本。此外，我们分别通过定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学法验证了胃癌组织和正常胃组织中 HHLA2mRNA 和蛋白的表达，发现胃癌组织中 HHLA2mRNA 和蛋白表达上调。此外，我们发现 HHLA2 高表达与胃癌的晚期临床分期、肿瘤浸润深度、淋巴结转移、远处转移和总生存期短相关。多变量 Cox 比例风险模型表明，HHLA2 高表达是胃癌患者总生存期的不良独立预后因素。总之，胃癌组织中 HHLA2 蛋白的过表达是恶性状态和不良预后的潜在危险因素。
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