title: HMGB1 overexpression correlates with poor prognosis in early-stage squamous cervical cancer.
abstract: High mobility group box 1 (HMGB1) is associated with tumor progression and a poor prognosis; microtubule-associated protein 1 light chain 3 (LC3) plays a critical role in autophagy. However, the roles of HMGB1 and LC3 in squamous cervical cancer (SCC) remain unclear. An array of 166 early-stage SCC, 62 cervical intraepithelial neoplasia (CIN), and 50 normal cervical tissue samples was assessed. HMGB1 and LC3 protein levels were examined by immunohistochemistry, and the associations of HMGB1 and LC3 levels with clinicopathological characteristics evaluated, to assess their prognosis significance. High nuclear HMGB1 levels were detected in 72.9% SCC cases; 16% cases showed cytoplasmic expression of HMGB1 in cancer cells with low nuclear expression. Interestingly, HMGB1 levels in SCC samples were significantly higher than CIN and control specimens, while lower LC3 expression was found in SCC samples (P < 0.001). Nuclear HMGB1 expression was weakly negatively correlated to LC3 amounts (r = -0.254, P = 0.001). High nuclear HMGB1 levels were associated with vascular metastasis (P < 0.05). In addition, cytoplasmic HMGB1 expression was associated with lymph node metastasis (P < 0.05). Furthermore, high nuclear HMGB1 levels and cytoplasmic HMGB1 expression predicted poor overall survival (OS) and disease-free survival (DFS). Meanwhile, high LC3 expression was associated with favorable prognosis. Multivariate analysis showed that both nuclear and cytoplasmic HMGB1 expressions were independent prognostic factors for overall- and disease-free survival, along with nodule metastasis. HMGB1 overexpression plays a significant role in SCC progression. Both nuclear and cytoplasmic HMGB1 are independent factors for poor prognosis in early-stage SCC.
authors.affiliation: Department of Pathology, Shanxi Medical University FenYang College, 032200, Fenyang, Shanxi Province, People's Republic of China. yirongxu@163.com.
authors.forename: Yirong
authors.identifier: http://orcid.org/0000-0001-9778-2835
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, Shanxi Medical University FenYang College, 032200, Fenyang, Shanxi Province, People's Republic of China.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology, Shanxi Medical University FenYang College, 032200, Fenyang, Shanxi Province, People's Republic of China.
authors.forename: Guangheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanxi Tumor Hospital (Shanxi Institute of Oncology), Taiyuan, Shanxi Province, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pathology, Shanxi Tumor Hospital (Shanxi Institute of Oncology), Taiyuan, Shanxi Province, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shanxi Medical University FenYang College, 032200, Fenyang, Shanxi Province, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chai
authors.affiliation: Department of Pathology, Shanxi Medical University FenYang College, 032200, Fenyang, Shanxi Province, People's Republic of China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanxi Tumor Hospital (Shanxi Institute of Oncology), Taiyuan, Shanxi Province, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pathology, Shanxi Fenyang Hospital, Fenyang, Shanxi Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins
keywords: Cervical cancer; High mobility group box 1 (HMGB1); Microtubule-associated protein 1 light chain 3 (LC3); Prognosis