{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:10:59Z","timestamp":1791263459626,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T00:00:00Z","timestamp":1152144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2006,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Hypoxia promotes tumorigenesis through the hypoxia\u2010inducible factor (HIF) pathway. There are 2 main homologues of the regulatory proteins, HIF\u20101\u03b1 and HIF\u20102\u03b1, which have different effects in genetic knock\u2010out experiments. Anemia may contribute to hypoxia by reducing oxygen delivery, but it is not known whether this influences HIF\u2010\u03b1 expression in tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>The expression of HIF\u20101\u03b1, HIF\u20102\u03b1, carbonic anhydrase\u20109 (CA\u20109), and peripheral hemoglobin (Hb) levels in 151 patients who underwent surgery for head and neck squamous cell carcinoma (HNSCC) were analyzed and related to outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>High HIF\u20101\u03b1 was expressed in 45 of 140 tumors (30%), HIF\u20102\u03b1 was expressed in 21 of 139 tumors (14%), and CA\u20109 was expressed in 56 of 149 tumors (62%). There was a positive correlation between HIF\u20101\u03b1 expression and HIF\u20102\u03b1 expression (<jats:italic>P<\/jats:italic> = .0001). HIF\u20101\u03b1 alone was associated with a worse disease\u2010specific survival (DSS) (<jats:italic>P<\/jats:italic> = .05) and disease\u2010free survival (DFS) (<jats:italic>P<\/jats:italic> = .03) in multivariate analyses. Nine percent of tumors expressed both high HIF\u20101\u03b1 and high HIF\u20102\u03b1. High HIF\u20101\u03b1\/high HIF\u20102\u03b1 expression was an independent prognostic factors in DSS (<jats:italic>P<\/jats:italic> = .04) and DFS (<jats:italic>P<\/jats:italic> = .005) in multivariate analyses. There was no correlation noted between Hb and HIF\u20101\u03b1, HIF\u20102\u03b1, or CA\u20109.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>HIF\u20101\u03b1 alone was correlated with DSS and DFS. The additive effect of HIF\u20102\u03b1 on poor prognosis suggested that different pathways may be regulated by HIF\u20102\u03b1. Anemia that was not related to HIF\u2010\u03b1 expression suggests that tumor intrinsic factors regulate HIF\u2010\u03b1; therefore, anemia may be a surrogate marker for other factors that affect outcome. Cancer 2006. \u00a9 2006 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.21983","type":"journal-article","created":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T16:50:03Z","timestamp":1152204603000},"page":"757-766","source":"Crossref","is-referenced-by-count":85,"title":["The relation between hypoxia\u2010inducible factor (HIF)\u20101\u03b1 and HIF\u20102\u03b1 expression with anemia and outcome in surgically treated head and neck cancer"],"prefix":"10.1002","volume":"107","author":[{"given":"Stuart C.","family":"Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan 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