Author:
Zhuang Hongkai,Zhang Zedan,Chen Bo,Tang Chenwei,Chen Xinming,Tan Wenliang,Yang Lei,Xie Zhiqin,Ma Xiaowu,Wang Qingbin,Wang Bingkun,Shang Changzhen,Chen Yajin
Abstract
AbstractHepatocellular carcinoma (HCC) has a desmoplastic and hypoxic tumor microenvironment (TME), resulting in poor prognosis and treatment resistance. This study aimed to construct a novel prognostic classifier to investigate the degree of hypoxia and immune profiles in HCC. Patients with HCC from public databases were classified into three HIF-1α clusters according to 16 reported HIF-1α-related genes. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α clusters. Then, an HIF-1α score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1α cluster. Besides, oncologic pathways and immune infiltration profiles were also investigated among HCCs with different HIF-1α scores. The reliable predictive abilities of the HIF-1α score system for patients’ survival were impressively suggested by the significant C-indexes and ROC analysis. All enrolled tumors were divided into high-, medium-, and low-HIF-1α score groups. Compared with the other two groups, the high HIF-1α score group exhibited highest enrichment of multiple oncogenic pathways, such as TNF-α signaling via NF-кB, IL6-JAK-STAT3 signaling, mTORC1 signaling, MYC signaling, Hedgehog signaling. Notably, higher HIF-1α scores correlated with advanced immunosuppressive TME. Besides, tumors with high HIF-1α scores represented high non-response rate to transcatheter arterial chemoembolization (TACE) and immune checkpoint blockade (ICB). In conclusion, we developed a novel HIF-1α score system to distinguish HCC with different degree of hypoxia and immune infiltration profiles.
Funder
the Guangdong Basic and Applied Basic Research Foundation
the Excellent Young Talent Program of Guangdong Provincial People’s Hospital
National Natural Science Foundation of China
China Postdoctoral Science Foundation
the program of Guangdong Provincial Clinical Research Center for Digestive Diseases
Publisher
Springer Science and Business Media LLC
Subject
Information Systems and Management,Computer Networks and Communications,Hardware and Architecture,Information Systems