Chromosome 11q13 amplification correlates with poor response and prognosis to PD-1 blockade in unresectable hepatocellular carcinoma

Kai Yan; Ding Zhang; Yanan Chen; Wenfeng Lu; Mengli Huang; Jinping Cai; Shiqing Chen; Ting Bei; Yuezong Bai; Jian Lv; Yong Fu; Haibin Zhang

doi:10.3389/fimmu.2023.1116057

Chromosome 11q13 amplification correlates with poor response and prognosis to PD-1 blockade in unresectable hepatocellular carcinoma

Front Immunol. 2023 Mar 28:14:1116057. doi: 10.3389/fimmu.2023.1116057. eCollection 2023.

Authors

Kai Yan¹, Ding Zhang², Yanan Chen², Wenfeng Lu¹, Mengli Huang², Jinping Cai², Shiqing Chen², Ting Bei², Yuezong Bai², Jian Lv³, Yong Fu¹, Haibin Zhang¹

Affiliations

¹ Department of Hepatic Surgery (V), The Third Affiliated Hospital of Naval Medical University, Shanghai, China.
² The Medical Department, 3D Medicines Inc., Shanghai, China.
³ Department of Thoracic Surgery, Changzheng Hospital, Shanghai, China.

Abstract

Background & aims: Little is known about molecular biomarkers that predict the response and prognosis in unresectable hepatocellular carcinoma (HCC) treated with programmed death (PD)-1 inhibitors.

Methods: A total of 62 HCC patients who underwent next-generation sequencing were retrospectively included in our department for this study. Patients with unresectable disease were subjected to systemic therapy. PD-1 inhibitors intervention (PD-1Ab) group and nonPD-1Ab group included 20 and 13 patients, respectively. Primary resistance was defined as initial on-treatment progression or progression with an initial stable disease of less than 6 months.

Results: Chromosome 11q13 amplification (Amp11q13) was the most common copy number variation in our cohort. Fifteen (24.2%) patients harbored Amp11q13 in our dataset. Patients with Amp11q13 showed higher level of Des-γ-carboxy-prothrombin (DCP), tumor number and were more prone to be combined with portal vein tumor thrombosis (PVTT). In the PD-1Ab group, the proportion of progressive disease (PD) in patients with Amp11q13 was significantly higher than that in patients with nonAmp11q13 (100% vs 33.3%, P=0.03). In the nonPD-1Ab group, the proportion of PD in patients with Amp11q13 and nonAmp11q13 had no significant difference (0% vs 11.1%, P>0.99). In the PD-1Ab group, the median progression-free survival (PFS) was 1.5 months in Amp11q13 patients vs 16.2 months in non-Amp11q13 patients (HR, 0.05; 95% CI 0.01-0.45; P = 0.0003). No significant difference was observed in the nonPD-1Ab group. Notably, we found that hyperprogressive disease (HPD) might be associated with Amp11q13. The increased density of Foxp3+ Treg cells in HCC patients with Amp11q13 might be one of potential mechanisms.

Conclusion: HCC patients with Amp11q13 are less likely to benefit from PD-1 blockade therapies. These findings may help guide the use of immunotherapy for HCC in routine clinical practice.

Keywords: chromosome 11q13 amplification; hepatocellular carcinoma; hyperprogressive disease; multiplex immunofluorescence; next-generation sequencing; programmed cell death protein-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / genetics
Chromosomes
Chromosomes, Human, Pair 13
DNA Copy Number Variations
Humans
Liver Neoplasms* / pathology
Prognosis
Programmed Cell Death 1 Receptor
Retrospective Studies
Venous Thrombosis*

Substances

Programmed Cell Death 1 Receptor

Grants and funding

This work was supported by grants from the Natural Science Foundation of China (No. 82172880) and the Science and Technology Commission of Shanghai Municipality (No. 20Y11909300).