HHLA2 overexpression is a novel biomarker of malignant status and poor prognosis in gastric cancer


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.

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Author information

LW and YL: conception and design and analysis of data. LW, LT, HC and SH: conducted the experiment, collected the data.

Correspondence to Yan Li.

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The authors declare no conflict of interest.

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This research complied with the Helsinki Declaration and was approved by the Ethics Committee of Jining No. 1 People’s Hospital (No. 20150013) and Affiliated Hospital of Jining Medical University (No. C-15042). Informed consent was gained from the study participants prior to their participation.

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Wei, L., Tang, L., Chang, H. et al. HHLA2 overexpression is a novel biomarker of malignant status and poor prognosis in gastric cancer. Human Cell 33, 116–122 (2020).

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  • HHLA2
  • Gastric cancer
  • Biomarker
  • Prognosis