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A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.

ABSTRACT:

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Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical resection (N?=?72) or LT (N?=?85) between 2000 and 2009 at three institutions were evaluated for the presence or absence of RVI. RVI was assessed for its ability to predict MVI and outcomes. Interobserver agreement for scoring RVI was substantial among five radiologists (??=?0.705; P?147 months), American Joint Committee on Cancer tumor-node-metastasis stage II (P?147 months), and in LT patients within Milan criteria (P?147 months). Positive RVI score also portended lower recurrence-free survival at 3 years versus negative RVI score (P?=?0.001; 27% vs. 62%).

Conclusion

RVI is a noninvasive radiogenomic biomarker that accurately predicts histological MVI in HCC surgical candidates. Its presence on preoperative CECT is associated with early disease recurrence and poor OS and may be useful for identifying patients less likely to derive a durable benefit from surgical treatment.

SUBMITTER: Banerjee S

PROVIDER: S-EPMC4654334 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.

Banerjee Sudeep S Wang David S DS Kim Hyun J HJ Sirlin Claude B CB Chan Michael G MG Korn Ronald L RL Rutman Aaron M AM Siripongsakun Surachate S Lu David D Imanbayev Galym G Kuo Michael D MD

Hepatology (Baltimore, Md.) 20150701 3

<h4>Unlabelled</h4>Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is an independent predictor of poor outcomes subsequent to surgical resection or liver transplantation (LT); however, MVI currently cannot be adequately determined preoperatively. Radiogenomic venous invasion (RVI) is a contrast-enhanced computed tomography (CECT) biomarker of MVI derived from a 91-gene HCC "venous invasion" gene expression signature. Preoperative CECTs of 157 HCC patients who underwent surgical re ...[more]

PMID: 25930992

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Project description:Background and aimsThe recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features.MethodsThree MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO.ResultsElevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs.ConclusionThis study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Project description:BACKGROUND:To investigate the potential value of volumetric iodine quantification using preoperative dual-energy computed tomography (DECT) for predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). METHODS:This retrospective study included patients with single HCC treated through surgical resection who underwent preoperative DECT. Quantitative DECT features, including normalized iodine concentration (NIC) to the aorta and mixed-energy CT attenuation value in the arterial phase, were three-dimensionally measured for peritumoral and intratumoral regions: (i) layer-by-layer analysis for peritumoral layers (outer layers 1 and 2; numbered in close order from the tumor boundary) and intratumoral layers (inner layers 1 and 2) with 2-mm layer thickness and (ii) volume of interest (VOI)-based analysis with different volume coverage (tumor itself; VOIO1, tumor plus outer layer 1; VOIO2, tumor plus outer layers 1 and 2; VOII1, tumor minus inner layer 1; VOII2, tumor minus inner layers 1 and 2). In addition, qualitative CT features, including peritumoral enhancement and tumor margin, were assessed. Qualitative and quantitative CT features were compared between HCC patients with and without MVI. Diagnostic performance of DECT parameters of layers and VOIs was assessed using receiver operating characteristic curve analysis. RESULTS:A total of 36 patients (24 men, mean age 59.9 ± 8.5 years) with MVI (n = 14) and without MVI (n = 22) were included. HCCs with MVI showed significantly higher NICs of outer layer 1, outer layer 2, VOIO1, and VOIO2 than those without MVI (P = 0.01, 0.04, 0.02, 0.02, respectively). Among the NICs of layers and VOIs, the highest area under the curve was obtained in outer layer 1 (0.747). Qualitative features, including peritumoral enhancement and tumor margin, and the mean CT attenuation of each layer and each VOI were not significantly different between HCCs with and without MVI (both P > 0.05). CONCLUSIONS:Volumetric iodine quantification of peritumoral and intratumoral regions in arterial phase using DECT may help predict the MVI of HCC.

Project description:Background: Previous studies reported that stress-induced phosphoprotein 1 (STIP1) can be secreted by hepatocellular carcinoma (HCC) cells and is increased in the serum of HCC patients. However, the therapy-monitoring and prognostic value of serum STIP1 in HCC remains unclear. Here, we aimed to systemically explore the prognostic significance of serum STIP1 in HCC. Methods: A total of 340 HCC patients were recruited to this study; 161 underwent curative resection and 179 underwent transcatheter arterial chemoembolization (TACE). Serum STIP1 was detected by enzyme-linked immunosorbent assay (ELISA). Optimal cutoff values for serum STIP1 in resection and TACE groups were determined by receiver operating characteristic (ROC) analysis. Prognostic value was assessed by Kaplan-Meier, log-rank, and Cox regression analyses. Predictive values of STIP1 for objective response (OR) to TACE and MVI were evaluated by ROC curves and logistic regression. Results: Serum STIP1 was significantly increased in HCC patients when compared with chronic hepatitis B patients or health donors (both P < 0.05). Optimal cutoff values for STIP1 in resection and TACE groups were 83.43 and 112.06 ng/ml, respectively. High pretreatment STIP1 was identified as an independent prognosticator. Dynamic changes in high STIP1 status were significantly associated with long-term prognosis, regardless of treatment approaches. Moreover, post-TACE STIP1 was identified as an independent predictor for OR, with a higher area under ROC curve (AUC-ROC) than other clinicopathological features. Specifically, pretreatment STIP1 was significantly increased in patients with microvascular invasion (MVI), and was confirmed as a novel, powerful predictor for MVI. Conclusions: Serum STIP1 is a promising biomarker for outcome evaluation, therapeutic response assessment, and MVI prediction in HCC. Integration serum STIP1 detection into HCC management might facilitate early clinical decision making to improve the prognosis of HCC.

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A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.

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A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma.

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