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. 2018 Mar 20:11:1563-1570.
doi: 10.2147/OTT.S160493. eCollection 2018.

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

Ziwen Zhu  1   2   3 , Weiguo Dong  1   2   3
Affiliations

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

Ziwen Zhu et al. Onco Targets Ther. .

Abstract

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: HHLA2; colorectal carcinoma; immune checkpoint; prognosis.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Representative photomicrographs of HHLA2 expression and CD8-positive T-cell infiltration in colorectal lesions. Notes: (A) Weak expression of HHLA2 in the adjacent intestinal epithelium tissues. (B) Positive expression of HHLA2 in the adjacent intestinal epithelium tissues. (C) High expression of HHLA2 in the CRC tissues. (D) CD8-positive expression in the T cells of stroma. (Original magnification: 400×).
Figure 2
Figure 2
Co-expression of HHLA2 and CD8 in the CRC tissues. Notes: (A and B) Low expression of HHLA2 (brown signal) and high CD8 (purple signal) in the same CRC tissues. (C and D) High expression of HHLA2 and low CD8 in the same CRC tissues. (Original magnification: A, C 100×; B, D 200×). Abbreviation: CRC, colorectal carcinoma.
Figure 3
Figure 3
CD8-positive cell-infiltrating status in CRC patients with HHLA2 high or low expression. Notes: The number of CD8-positive cells in the high-HHLA2 group was significantly lower than the number in the low-HHLA2 group. *P=0.023 by two independent t-tests. Abbreviation: CRC, colorectal carcinoma.
Figure 4
Figure 4
Correlation of HHLA2 expression level and overall survival in patients with CRC. Notes: (A) Thirty-three patients with low HHLA2 expression showed better overall survival than 30 patients with high HHLA2 expression (P=0.035). (B) High expression of HHLA2 and low CD8 showed no significant prognostic value for the overall survival of patients with CRC (P=0.185). Abbreviation: CRC, colorectal carcinoma.
See this image and copyright information in PMC

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