Dataset Information

RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma.

ABSTRACT: Adjuvant transcatheter arterial chemoembolization (TACE) protects against hepatocellular carcinoma (HCC) and is associated with reduced disease recurrence and improved outcome after surgery. However, deterioration of liver function after TACE negatively impacts the patient prognosis and limits it use as an option to prolong survival. We analyzed two independent cohorts that included a total of 510 patients with HCC who had undergone tumor resection. Immunohistochemistry assay was used to measure RPB5-mediating protein (RMP) expression and assessed their association with recurrence rate and response to therapy with adjuvant TACE. In patients with HCC, the expression of RMP in tumor is associated with age, gender, tumor size, portal venous invasion, TNM stages, BCLC stages and overall survival. Among patients with high RMP expression, adjuvant TACE after resection was associated with early recurrence. Even in the patients with small tumor size (no more than 5 cm) or no venous invasion, RMP status is associated with response to adjuvant TACE. RMP status in tumors may be a useful marker in estimating prognosis in patients with HCC and in assisting in the selection of patients who are likely to benefit from adjuvant TACE to prevent relapse.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4413664 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma.

Zhang Jian J Jiang Tian-Yi TY Jiang Bei-Ge BG Yang Chun C Tan Ye-Xiong YX Yang Ning N Pan Yu-Fei YF Ding Zhi-Wen ZW Yang Guang-Zhen GZ Wu Meng-Chao MC Dong Li-Wei LW Wang Hong-Yang HY

Oncotarget 20150201 5

Adjuvant transcatheter arterial chemoembolization (TACE) protects against hepatocellular carcinoma (HCC) and is associated with reduced disease recurrence and improved outcome after surgery. However, deterioration of liver function after TACE negatively impacts the patient prognosis and limits it use as an option to prolong survival. We analyzed two independent cohorts that included a total of 510 patients with HCC who had undergone tumor resection. Immunohistochemistry assay was used to measure ...[more]

PMID: 25605019

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Project description:Background and Aims: The tumor microenvironment can be divided into inflamed, immune-excluded and immune-desert phenotypes according to CD8+ T cell categories with differential programmed cell death protein 1 (PD-L1) expression. The study aims to construct a novel immunotype-based risk stratification model to predict postsurgical survival and adjuvant trans-arterial chemoembolization (TACE) response in patients with hepatocellular carcinoma (HCC). Methods: A total of 220 eligible HCC patients participated in this study. CD8 + T cell infiltration and PD-L1 expression mode were estimated by immunohistochemical staining. A risk stratification model was developed and virtualized by a nomogram that integrated these independent prognostic factors. The postoperative prognosis and adjuvant TACE benefits were evaluated with a novel immunotype-based risk stratification model. Results: A total of 220 patients were finally identified. Immune-desert, immune-excluded, and inflamed immunotypes represented 45%, 24%, and 31% of HCC, respectively. Univariate and multivariate analyses identified immunotype and PD-L1 expression mode as independent prognostic factors for overall survival time (OS) and recurrence-free survival time (RFS). The nomogram was constructed by integrating immunotype, PD-L1 expression, Barcelona Clinic Liver Cancer (BCLC) stage and tumor grade. The C-index was 0.794 in the training cohort and 0.813 in the validation cohort. A risk stratification system was constructed based on the nomogram classifying HCC patients into 3 risk groups. The average OS times in the low-risk, intermediate-risk and high-risk groups in all cohorts were 77.1 months (95% CI 71.4-82.9), 53.7 months (95% CI 48.2-59.2), and 25.6 months (95% CI 21.4-29.7), respectively. Further analysis showed that OS was significantly improved by adjuvant TACE in the low- and intermediate-risk groups (P=0.041 and P=0.010, respectively) but not in the high-risk group (P=0.398). Conclusion: A novel immunotype-based risk stratification model was built to predict postoperative prognosis and adjuvant TACE benefit in HCC patients. These tools can assist in building a more customized method of HCC treatment.

Project description:BackgroundHepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies.MethodsWe analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases.ResultsThe HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance.ConclusionThis study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.

Dataset Information

RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma.

Publications

RMP predicts survival and adjuvant TACE response in hepatocellular carcinoma.

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