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Overexpression of HHLA2, a member of the B7 family, is associated with worse survival in human colorectal carcinoma

Authors Zhu Z, Dong W

Received 21 December 2017

Accepted for publication 7 February 2018

Published 20 March 2018 Volume 2018:11 Pages 1563—1570

DOI https://doi.org/10.2147/OTT.S160493

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada


Ziwen Zhu,1–3 Weiguo Dong1–3

1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Digestive System Disease, Wuhan, People’s Republic of China; 3Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China

Background: Colorectal carcinoma (CRC) is one of the most common malignancies, and immunotherapy has opened a new field of cancer treatment in recent years. Generally, CRC does not benefit from immunotherapy. HHLA2, a member of the B7 family, is a novel immune checkpoint molecule, and the prognostic value of HHLA2 in CRC patients and the association between HHLA2 expression and clinicopathological characteristics remains unknown.
Materials and methods: This study included 63 patients diagnosed with CRC, and their resected specimens were obtained and constructed as a tissue microarray. Expression of HHLA2 and CD8 was detected by the double immunohistochemistry method. Based on follow-up data, correlations of HHLA2 expression and clinicopathological features, including overall survival, in CRC patients were evaluated.
Results: High HHLA2 expression was detected in CRC tumor tissues, compared to the adjacent noncancerous tissues. HHLA2 expression level was significantly related to the depth of invasion (P=0.044) and CD8+ T-cell infiltration status (P=0.016), and predicted high mortality rate (P=0.035). HHLA2 acted as an independent predictive factor in the overall survival of CRC patients (P=0.039, hazard ratio=2.162, 95% CI 1.041–3.084).
Conclusion: HHLA2 expression is upregulated in CRC patients, and HHLA2 is an independent prognostic factor of overall survival of CRC patients. High HHLA2 expression is closely correlated with CD8 T-cell infiltration status and can predict poor prognosis in CRC patients.

Keywords: colorectal carcinoma, HHLA2, immune checkpoint, prognosis

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