Dataset Information

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection.

ABSTRACT: Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.

SUBMITTER: Miller H

PROVIDER: S-EPMC7767259 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection.

Miller Hannah H Czigany Zoltan Z Lurje Isabella I Reichelt Sophie S Bednarsch Jan J Strnad Pavel P Trautwein Christian C Roderburg Christoph C Tacke Frank F Gaisa Nadine Therese NT Knüchel-Clarke Ruth R Neumann Ulf Peter UP Lurje Georg G

Cancers 20201218 12

Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primar ...[more]

PMID: 33352897

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Project description:BackgroundThe role of autophagy-related markers as the prognostic factor of post-operative hepatocellular carcinoma (HCC) recurrence remained controversial.MethodsOverall, 535 consecutive HCC patients undergoing curative resection from 2010 to 2014 were followed and classified with early (ER, <2 years) or late recurrence (LR). Autophagy-related markers, LC3, Beclin-1, and p62 expression was immunohistochemically assessed in HCC and adjacent non-tumor (ANT) tissues.ResultsHCC recurred in 245 patients: 116 with ER and 129 with LR. The cumulative incidence of recurrence at 1, 3, 5, and 7 years was 9.7%, 33.9%, 53.3%, and 66.3%, respectively. In multivariate analysis, HCC recurrence was significantly associated with low LC3 expression in tumor and ANT tissues, HCC tissues only and ANT tissues only (hazard ratio/95% confidence interval: 6.12/2.473-17.53, 4.18/1.285-13.61, and 1.89/1.299-2.757) and macrovascular invasion (1.63/1.043-2.492) and cirrhosis (1.59/1.088-2.326). ER was significantly associated with low LC3 expression in tumor and ANT tissues, HCC tissues only and ANT tissues only (6.54/2.934-15.81, 3.26/1.034-10.27, and 2.09/1.313-3.321) and macrovascular and microvascular invasion (2.65/1.306-5.343 and 2.55/1.177-5.504). LR was significantly associated with low LC3 expression in tumor and ANT tissues, HCC tissues only and ANT tissues only (5.02/1.372-18.83, 3.19/1.13-12.09, and 1.66/1.051-2.620) and cirrhosis (1.66/1.049-2.631). Patients with low and high LC3 expression in tumor and ANT tissues showed a 5-year cumulative recurrence of 94.3% and 41.7%, respectively (p < 0.001).ConclusionsThe high LC3 expression in the tumor and liver microenvironments is significantly associated with lower HCC recurrence. Furthermore, tumor characteristics and liver microenvironment were also significantly associated with ER and LR, respectively.Translational impactThe analysis for LC3 expression in both the HCC and ANT tissues could identify patients at risk of HCC recurrence.

Project description:Background & aimsMetabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed.MethodsBetween 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events.ResultsIn total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002).ConclusionsPatients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors.Impact and implicationsMetabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Dataset Information

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection.

Publications

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection.

Similar Datasets

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