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Co-expression of KIAA1199 and hypoxia-inducible factor 1α is a biomarker for an unfavorable prognosis in hepatocellular carcinoma.

ABSTRACT: Advanced studies demonstrated that hypoxic stress induced KIAA1199 expression leading to enhanced cell migration. KIAA1199 is a protein related with cancer metastasis. Hypoxia inducible factor 1α (HIF-1α) is a transcriptional factor that maintains oxygen homeostasis. Both KIAA1199 and HIF-1α were upregulated in many human cancers. In the present study, co-expression of KIAA1199 and HIF-1α was evaluated for the clinicopathological characteristics and survival in hepatocellular carcinoma (HCC). Clinical-pathological information and follow-up data were collected from 152 HCC patients. KIAA1199 and HIF-1α expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slide. Correlations between clinical features and the expression of KIAA1199 and HIF-1α were evaluated by Chi-square test, Kaplan-Meier curves and multivariate Cox regression analysis. The frequency of KIAA1199 high expression was higher in HCC than adjacent tissue. KIAA1199(H)/HIF-1α(H) tumors were more frequently of TNM (P = .011), tumor size (P = .021), vascular invasion (P = .002) and HBV (P = .001). In survival analysis, KIAA1199(H)/HIF-1α(H) patients had the worst prognosis. Using the combination of the two parameters increased the prognostic value (P < .01 vs P = .03). KIAA1199 in combination with HIF-1α expression tends to indicate a more accurate prognosis.

SUBMITTER: Wang D

PROVIDER: S-EPMC7738140 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Co-expression of KIAA1199 and hypoxia-inducible factor 1α is a biomarker for an unfavorable prognosis in hepatocellular carcinoma.

Wang Dan D Lu Shu S Zhang Xiaojing X Huang Linlin L Zhao Hui H

Medicine 20201201 50

Advanced studies demonstrated that hypoxic stress induced KIAA1199 expression leading to enhanced cell migration. KIAA1199 is a protein related with cancer metastasis. Hypoxia inducible factor 1α (HIF-1α) is a transcriptional factor that maintains oxygen homeostasis. Both KIAA1199 and HIF-1α were upregulated in many human cancers. In the present study, co-expression of KIAA1199 and HIF-1α was evaluated for the clinicopathological characteristics and survival in hepatocellular carcinoma (HCC). Cl ...[more]

PMID: 33327261

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Project description:BackgroundExtensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.MethodsA comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.ResultsCompared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.ConclusionHCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.Author summaryClonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

Dataset Information

Co-expression of KIAA1199 and hypoxia-inducible factor 1α is a biomarker for an unfavorable prognosis in hepatocellular carcinoma.

Publications

Co-expression of KIAA1199 and hypoxia-inducible factor 1α is a biomarker for an unfavorable prognosis in hepatocellular carcinoma.

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