Integration of OV6 expression and CD68+ tumor-associated macrophages with clinical features better predicts the prognosis of patients with hepatocellular carcinoma

Ming-Da Wang; Hao Xiang; Ling Zhang; Chao Wang

doi:10.1016/j.tranon.2022.101509

Integration of OV6 expression and CD68⁺ tumor-associated macrophages with clinical features better predicts the prognosis of patients with hepatocellular carcinoma

Transl Oncol. 2022 Nov:25:101509. doi: 10.1016/j.tranon.2022.101509. Epub 2022 Aug 26.

Authors

Ming-Da Wang¹, Hao Xiang², Ling Zhang³, Chao Wang⁴

Affiliations

¹ Department of Urinary Surgery, Shanghai Pudong Gongli Hospital, Shanghai 200135, China; Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Navy Medical University, Shanghai 200433, China.
² The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou 563000, China.
³ Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address: zling1206@shsmu.edu.cn.
⁴ Department of Urinary Surgery, Shanghai Pudong Gongli Hospital, Shanghai 200135, China; Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Shanghai Pudong Gongli Hospital, Shanghai 200135, China. Electronic address: superwang2012@aliyun.com.

Abstract

Background: Reliable prognostic indicators for accurately predicting postoperative outcomes in Hepatocellular carcinoma (HCC) patients are lacking. Although cancer stem-like cells (CSCs) and tumor-associated macrophages (TAMs) in tumor microenvironment are implicated in the occurrence and development of HCC, whether the combination of CSC biomarkers and TAM populations could achieve better performance in predicting the prognosis of patients with HCC has been rarely reported.

Methods: A total of 306 HCC patients were randomly divided into the training and validation cohorts at a 1:1 ratio, and the expression of OV6 and CD68 was assessed using immunohistochemistry in HCC samples. The prognostic value of these biomarkers for post-surgical survival and recurrence were evaluated by the curve of receiver operating characteristic and multivariate Cox regression analyses.

Results: The density of OV6⁺ CSCs was positively correlated with the infiltration of CD68⁺ TAMs in HCC. Both high OV6 expression and CD68⁺ TAM infiltration was closely associated with poor overall survival (OS) and progression-free survival (PFS) of HCC patients. Moreover, overexpression of OV6 and infiltration of CD68⁺ TAMs were identified as independent prognostic factors for OS and PFS after liver resection. The integration of OV6 and CD68 with tumor size and microvascular invasion exhibited highest C-index value for survival predictivity in HCC patients than any other biomarkers or clinical indicators alone.

Conclusion: Incorporating intratumoral OV6 expression and CD68⁺ TAMs infiltration with established clinical indicators may serve as a promising prognostic signature for HCC, and could more accurately predict the clinical outcomes for HCC patients after liver resection.

Keywords: CD68; Cancer stem-like cells; Hepatocellular carcinoma; OV6; Prognosis; Tumor-associated macrophage.