Clinically Relevant Biomarkers to Select Patients for Targeted Inhibitor Therapy after Resection of Hepatocellular Carcinoma

Patel, Sameer H.; Kneuertz, Peter J.; Delgado, Maria; Kooby, David A.; Staley, Charles A.; El‐Rayes, Bassel F.; Kauh, John S.; Sarmiento, Juan M.; Hanish, Steven I.; Cohen, Cynthia; Farris, Alton B.; Maithel, Shishir K.

doi:10.1245/s10434-011-1775-3

Cited by 20 publications

(24 citation statements)

References 22 publications

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“…In accordance with other previous studies [14, 17, 18], our study also demonstrated that strong PDGFRα expression in tumor sites was associated with poor survival outcome after HCC resection. However, the expression of PDGFRα did not necessarily associated with underlying liver fibrosis/cirrhosis or the expression of PDGFRα in adjacent non-tumor site of the liver.…”

Section: Discussionsupporting

confidence: 93%

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Kim

et al. 2017

Oncotarget

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Background and AimsPlatelet-derived growth factor receptor alpha (PDGFRα) is suggested as a prognosis marker for hepatocellular carcinoma (HCC). Since PDGFRα is also known as a marker for activated hepatic stellate cells (HSCs), this study aimed to investigate whether PDGFRα expression in HCC was dependent on the background liver fibrous condition.ResultsStrong PDGFRα expression in the tumor lesions was associated with decreased survival after curative HCC resection. Expression of PDGFRα in the tumor correlated with increased collagen α1(I), lecithin retinol acyltransferase, and smooth muscle α-actin suggesting increased HSCs in tumor sites. The expression of PDGFRα in the tumor sites was associated neither with underlying liver fibrosis/cirrhosis nor with the expression of PDGFRα in adjacent non-tumor sites of the liver.Materials and MethodsPatients with HCC who underwent liver resection as curative treatment were included in this study. Using liver samples of 95 patients, tissue microarray was constructed and immunohistochemical study of PDGFRα was conducted in both tumor and non-tumor sites. PDGFRα expression in tumor and matching non-tumor sites was compared. Freshly frozen liver tissue specimens of 16 HCC patients were used for gene expression analysis of PDGFRα and fibrosis related genes.ConclusionsOur results suggest that PDGFRα overexpression in HCC is a prognostic marker independent of adjacent non-tumor site liver fibrosis status.

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Section: Discussionsupporting

confidence: 93%

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Kim

et al. 2017

Oncotarget

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“…In breast and prostate cancer, stromal PDGFRb expression correlates with shorter survival (6,7). Increased expression of PDGFRb is also associated with poor overall survival in angiosarcoma (8), hepatocellular carcinoma (9), and a subset of non-small cell lung cancers (10).…”

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confidence: 99%

Imaging of Platelet-Derived Growth Factor Receptor β Expression in Glioblastoma Xenografts Using Affibody Molecule¹¹¹In-DOTA-Z09591

et al. 2014

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“…Some key mediators of these pathways include the following: VEGFR, Raf, and PDGFR. These proteins have increasingly become important for the treatment of HCC because they are targeted by multikinase inhibitors [25]. Sorafenib is a multiple kinase inhibitor that specifically acts on VEGFR 2-3, PDGFR-β and Raf kinases (Raf-1) and prolongs survival time in patients with advanced HCC [12].…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence

et al. 2016

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Background and AimsLiver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence.ResultsMost of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211–2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017–1.543; P = 0.046) in HCC patients who underwent radical hepatic resection.Patients and MethodsWe retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis.ConclusionsHCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.

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Clinically Relevant Biomarkers to Select Patients for Targeted Inhibitor Therapy after Resection of Hepatocellular Carcinoma

Abstract: High expression of PDGFR-α and PDGFR-β may be independently associated with decreased OS irrespective of margin status, MELD score, and tumor extent. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting.

Cited by 20 publications

References 22 publications

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Imaging of Platelet-Derived Growth Factor Receptor β Expression in Glioblastoma Xenografts Using Affibody Molecule¹¹¹In-DOTA-Z09591

Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence

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Clinically Relevant Biomarkers to Select Patients for Targeted Inhibitor Therapy after Resection of Hepatocellular Carcinoma

Abstract: High expression of PDGFR-α and PDGFR-β may be independently associated with decreased OS irrespective of margin status, MELD score, and tumor extent. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting.

Cited by 20 publications

References 22 publications

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Platelet-derived growth factor receptor α in hepatocellular carcinoma is a prognostic marker independent of underlying liver cirrhosis

Imaging of Platelet-Derived Growth Factor Receptor β Expression in Glioblastoma Xenografts Using Affibody Molecule111In-DOTA-Z09591

Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence

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Imaging of Platelet-Derived Growth Factor Receptor β Expression in Glioblastoma Xenografts Using Affibody Molecule¹¹¹In-DOTA-Z09591