PMID- 36329448 OWN - NLM STAT- MEDLINE DCOM- 20221107 LR - 20221108 IS - 1477-7819 (Electronic) IS - 1477-7819 (Linking) VI - 20 IP - 1 DP - 2022 Nov 4 TI - HIF-1alpha and Caspase-3 expression in aggressive papillary thyroid carcinoma. PG - 353 LID - 10.1186/s12957-022-02815-8 [doi] LID - 353 AB - BACKGROUND: Tumor cells adapt to hypoxia by regulating transcription factors that involved in regulation of metabolism, angiogenesis, cell proliferation, and apoptosis. Under hypoxic conditions, hypoxia-inducible factor-1 (HIF-1), consisting of HIF-1alpha and HIF-1beta subunits, acts as a key transcription factor mediating the adaptive cellular responses. Caspase-3 is a key apoptosis-related protease that plays a role in tumor growth and development. Studies have shown that caspase-3 could be regulated by HIF-1alpha under pathological conditions. Therefore, HIF-1alpha and caspase-3 expression may be related to the poor prognosis of tumors. In this study, we analyzed the possible relationships between these two signaling factors in correlation with the clinical behavior of PTC. METHODS: We detected the expression levels of HIF-1alpha and caspase-3 in 70 samples of PTC and para-cancerous tissues (control group) by immunohistochemistry (IHC). Furthermore, various clinicopathological parameters were assessed to determine their correlations with HIF-1alpha and caspase-3 expressions. RESULTS: First, HIF-1alpha and caspase-3 expressions (60% and 37.1%, respectively) increased significantly in the PTC samples as compared to normal tissues (2.9% for both HIF-1alpha and caspase-3) (p < 0.05) as determined by IHC. Second, although there was no significant difference between the expression of HIF-1alpha and caspase-3 in regard to gender, age distribution, tumor size, lymph node metastasis, and BRAF(V600E) mutation (all p > 0.05), HIF-1alpha and caspase-3 expressions were associated with capsule invasion and cell subtypes of PTC (p < 0.05). The percent positivity of caspase-3 expression in tall-cell variant (TCV) was the highest (63.6%). Third, HIF-1alpha expression was positively correlated with that of caspase-3 (r(s) = 0.326; p < 0.05). CONCLUSIONS: Overexpression of HIF-1alpha and caspase-3 is associated with carcinogenesis. These factors might serve as promising predictors of aggressive PTC. These findings also suggest their potential as therapeutic targets. CI - (c) 2022. The Author(s). FAU - Zhang, Lili AU - Zhang L AD - Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Shi, Baixue AU - Shi B AD - Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Hu, Mingyang AU - Hu M AD - Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Qian, Linxue AU - Qian L AD - Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China. qianlinxue2002@163.com. LA - eng PT - Journal Article DEP - 20221104 PL - England TA - World J Surg Oncol JT - World journal of surgical oncology JID - 101170544 RN - EC 3.4.22.- (Caspase 3) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) SB - IM MH - Humans MH - Thyroid Cancer, Papillary MH - Caspase 3 MH - Immunohistochemistry MH - *Hypoxia-Inducible Factor 1, alpha Subunit MH - *Thyroid Neoplasms/pathology MH - Hypoxia PMC - PMC9635136 OTO - NOTNLM OT - Caspase-3 OT - HIF-1alpha OT - Thyroid carcinoma COIS- The authors declare that they have no competing interests. EDAT- 2022/11/05 06:00 MHDA- 2022/11/08 06:00 PMCR- 2022/11/04 CRDT- 2022/11/04 00:49 PHST- 2022/05/01 00:00 [received] PHST- 2022/10/16 00:00 [accepted] PHST- 2022/11/04 00:49 [entrez] PHST- 2022/11/05 06:00 [pubmed] PHST- 2022/11/08 06:00 [medline] PHST- 2022/11/04 00:00 [pmc-release] AID - 10.1186/s12957-022-02815-8 [pii] AID - 2815 [pii] AID - 10.1186/s12957-022-02815-8 [doi] PST - epublish SO - World J Surg Oncol. 2022 Nov 4;20(1):353. doi: 10.1186/s12957-022-02815-8.