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Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

ABSTRACT: Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulatory T cell (Treg) infiltration in tissue microarrays in primary cohort comprising 210 randomly selected HCC patients who underwent curative resection. The results were further verified in an independent validation cohort of 138 HCC patients.Patients with higher expression of IL-35 are more likely to suffer postoperative recurrence. Interleukin-35 was also identified as an independent prognostic factor for recurrence free survival in multivariate analysis. No correlation was detected between IL-35 expression and Foxp3(+) Treg infiltration, whereas significant positive correlation was found between IL-35 expression and CD39(+)Foxp3(+) Treg infiltration. In addition, CD39(+)Foxp3(+) Treg infiltration was also an independent predictor for postoperative recurrence. The nomogram comprising tumour size, tumour vascular invasion, IL-35 and CD39(+)Foxp3(+) Tregs had better predictive accuracy when compared with BCLC stage for RFS. These results were further validated in the validation cohort.Our data suggest for the first time that IL-35 expression correlates with HCC aggressiveness and emerged as a novel independent prognostic factor for recurrence, thus conferring the rationale to develop a novel therapy of targeting IL-35. Furthermore, IL-35 should be incorporated into nomogram to generate a more accurate predictive model.

SUBMITTER: Fu YP

PROVIDER: S-EPMC4984866 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

Fu Yi-Peng YP Yi Yong Y Cai Xiao-Yan XY Sun Jian J Ni Xiao-Chun XC He Hong-Wei HW Wang Jia-Xing JX Lu Zhu-Feng ZF Huang Jin-Long JL Cao Ya Y Zhou Jian J Fan Jia J Qiu Shuang-Jian SJ

British journal of cancer 20160322 7

<h4>Background</h4>Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.<h4>Methods</h4>Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulat ...[more]

PMID: 27002937

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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.

Dataset Information

Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

Publications

Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.

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