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Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment.

ABSTRACT: Fibronectin, a matrix glycoprotein aberrantly expressed in various tumor cells, is a known candidate biomarker for the early diagnosis of hepatocellular carcinoma (HCC). In this study, we investigated whether serum fibronectin levels could predict tumor recurrence in patients with early-stage HCC after curative treatment. A total of 83 patients who showed complete response after initial curative treatment were included. The levels of serum fibronectin at baseline and 4-6 weeks after initial treatment were analyzed with regard to their associations with recurrence. Multivariate logistic regression analyses were performed to construct a prognostic nomogram. Baseline fibronectin levels were not significantly correlated with tumor size, number, stage, and serum α-fetoprotein levels. However, decrease in serum fibronectin levels after treatment was significantly associated with reduced HCC recurrence in multivariate logistic regression (odds ratio, 0.009; p < 0.001). Furthermore, a nomogram consisting of gender and changes in serum fibronectin showed a good discriminatory capability for the prediction of HCC recurrence with an area under the receiver-operating curve of 0.87. In conclusion, changes in serum fibronectin levels may be a surrogate indicator for assessment of treatment response in patients with early HCC after curative treatment.

SUBMITTER: Kim SA

PROVIDER: S-EPMC7719187 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment.

Kim Sun Ah SA Cho Eun Ju EJ Lee Sungyoung S Cho Young Youn YY Kim Boram B Yoon Jung-Hwan JH Park Taesung T

Scientific reports 20201204 1

Fibronectin, a matrix glycoprotein aberrantly expressed in various tumor cells, is a known candidate biomarker for the early diagnosis of hepatocellular carcinoma (HCC). In this study, we investigated whether serum fibronectin levels could predict tumor recurrence in patients with early-stage HCC after curative treatment. A total of 83 patients who showed complete response after initial curative treatment were included. The levels of serum fibronectin at baseline and 4-6 weeks after initial trea ...[more]

PMID: 33277619

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Project description:OBJECTIVE:To construct a prediction model based on peritumoral radiomics signatures from CT images and investigate its efficiency in predicting early recurrence (ER) of hepatocellular carcinoma (HCC) after curative treatment. MATERIALS AND METHODS:In total, 156 patients with primary HCC were randomly divided into the training cohort (109 patients) and the validation cohort (47 patients). From the pretreatment CT images, we extracted 3-phase two-dimensional images from the largest cross-sectional area of the tumor. A region of interest (ROI) was manually delineated around the lesion for tumoral radiomics (T-RO) feature extraction, and another ROI was outlined with an additional 2 cm peritumoral area for peritumoral radiomics (PT-RO) feature extraction. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for feature selection and model construction. The T-RO and PT-RO models were constructed. In the validation cohort, the prediction efficiencies of the two models and peritumoral enhancement (PT-E) were evaluated qualitatively by receiver operating characteristic (ROC) curves, calibration curves and decision curves and quantitatively by area under the curve (AUC), the category-free net reclassification index (cfNRI) and integrated discrimination improvement values (IDI). RESULTS:By comparing AUC values, the prediction accuracy in the validation cohort was good for the PT-RO model (0.80 vs. 0.79, P = 0.47) but poor for the T-RO model (0.82 vs. 0.62, P < 0.01), which was significantly overfitted. In the validation cohort, the ROC curves, calibration curves and decision curves indicated that the PT-RO model had better calibration efficiency and provided greater clinical benefits. CfNRI indicated that the PT-RO model correctly reclassified 47% of ER patients and 32% of non-ER patients compared to the T-RO model (P < 0.01); additionally, the PT-RO model correctly reclassified 24% of ER patients and 41% of non-ER patients compared to PT-E (P = 0.02). IDI indicated that the PT-RO model could improve prediction accuracy by 0.22 (P < 0.01) compared to the T-RO model and by 0.20 (P = 0.01) compared to PT-E. CONCLUSION:The CT-based PT-RO model can effectively predict the ER of HCC and is more efficient than the T-RO model and the conventional imaging feature PT-E.

Project description:Background and aimsPrimary hepatocellular carcinoma (HCC) is usually presented in inflamed fibrotic/cirrhotic liver with extensive lymphocyte infiltration. We examined the associations between the HCC early recurrence and alterations in serum levels of inflammatory cytokines.MethodsA cohort of 105 HCC patients with chronic hepatitis B virus infection were included. Pre-therapy, we quantified their serum concentrations of Th1-, Th2-, Th17-, Treg-related, and other cytokines that have been reported to be associated with poor prognosis in human cancers. IL17-producing T-cells were generated in vitro from HCC patients and co-cultured with HCC cell lines separated by a 0.4 µM transwell.ResultsAll the 105 cases of HCC patients had liver cirrhosis. The patients who suffered from HCC early recurrence had higher pre-therapy serum levels of IL17 and lower levels of IL10 than those who did not suffer from recurrence after curative hepatectomy. After adjustment for general tumor clinicopathological factors, elevated serum levels of IL17 (? 0.9 pg/ml) was found to be an independent risk factor for HCC early recurrence with a hazard ratio of 2.46 (95%CI 1.34-4.51). Patients with bigger tumors (>5 cm in diameter) and elevated serum levels of IL17 had the highest risk of early recurrence as compared to those with only one of these factors (P = 0.009) or without any (P<0.001). These factors showed similar effects on the HCC patient overall survival. Intrahepatic infiltrated T-cells in HCC patients were identified as the major IL17-producing cells. Proliferation of HCC cells, QGY-7703, was augmented QGY-7703, was augmented in the presence of IL17-producing T-cells. This effect diminished after neutralizing antibody against human IL17A or TNF? was included.ConclusionBoth tumors and IL17 from liver infiltrated T-cells contributed to HCC early recurrence and progression after curative resection. Pre-therapy serum IL17 levels may serve as an additional indicator for predicting high-risk patients.

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Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment.

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Changes in serum fibronectin levels predict tumor recurrence in patients with early hepatocellular carcinoma after curative treatment.

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