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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-1\u03b1 clusters according to 16 reported HIF-1\u03b1-related genes. Then, an HIF-1\u03b1 score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1\u03b1 clusters. Then, an HIF-1\u03b1 score system was constructed based on nine overlapping differentially expressed genes (ODEGs) among various HIF-1\u03b1 cluster. Besides, oncologic pathways and immune infiltration profiles were also investigated among HCCs with different HIF-1\u03b1 scores. The reliable predictive abilities of the HIF-1\u03b1 score system for patients\u2019 survival were impressively suggested by the significant C-indexes and ROC analysis. All enrolled tumors were divided into high-, medium-, and low-HIF-1\u03b1 score groups. Compared with the other two groups, the high HIF-1\u03b1 score group exhibited highest enrichment of multiple oncogenic pathways, such as TNF-\u03b1 signaling via NF-\u043aB, IL6-JAK-STAT3 signaling, mTORC1 signaling, MYC signaling, Hedgehog signaling. Notably, higher HIF-1\u03b1 scores correlated with advanced immunosuppressive TME. Besides, tumors with high HIF-1\u03b1 scores represented high non-response rate to transcatheter arterial chemoembolization (TACE) and immune checkpoint blockade (ICB). In conclusion, we developed a novel HIF-1\u03b1 score system to distinguish HCC with different degree of hypoxia and immune infiltration profiles.<\/jats:p>","DOI":"10.1186\/s40537-023-00752-1","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T06:02:08Z","timestamp":1684735328000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic stratification based on HIF-1\u03b1 signaling for evaluating hypoxia status and immune landscape in hepatocellular carcinoma"],"prefix":"10.1186","volume":"10","author":[{"given":"Hongkai","family":"Zhuang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zedan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenwei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenliang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingkun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changzhen","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"752_CR1","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1056\/NEJMra1713263","volume":"380","author":"A Villanueva","year":"2019","unstructured":"Villanueva A. 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