Dataset Information

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients.

ABSTRACT: Purpose: To investigate the correlation between the expression of PD-L1, SOCS3 and immune-related biomarkers CD276, CD4, CD8 in hepatocellular carcinoma (HCC) and further determine the relationship with clinicopathologic characteristics and the prognostic value of their co-expression in HCC patients. Methods: We assessed the expression of PD-L1, CD276, SOCS3, CD4 and CD8 by immunohistochemistry in tumor tissue from 74 HCC patients who underwent curative hepatectomy. Results: High expression of PD-L1 was significantly associated with high Edmondson grade (p<0.01) and elevated enzyme (p=0.037); high expression of CD276 was significantly correlated with high Edmondson grade (p=0.021); high expression of SOCS3 was significantly associated with age (p=0.026) and tumor size (p=0.041), while PD-L1 showed no significant correlation. The expression of PD-L1, CD276, SOCS3 protein and other clinicopathological factors (sex, vascular invasion, tumor number, tumor capsule, pT stage, liver cirrhosis, HBsAg, TBiL, AFP) showed no significant correlation (p>0.05). High expression of CD8 was respectively significantly associated with worse overall survival (OS) (p=0.002). There was no significantly difference between CD4 and CD8 high-expression and overall survival (OS) (p=0.100). Both high expression of PD-L1 (p=0.003) and low expression of SOCS3 (p=0.015) was significantly associated with worse overall survival (OS). But CD276 only had a trendency (p=0.166). Additionally, multivariate Cox regression models implied that PD-L1, SOCS3, as well as both CD4 and CD8 was an independent prognostic factor for OS (p<0.05). Furthermore, HCC patients with PD-L1 low-expression and SOCS3 high-expression had a better prognostic according to the different pT stages (p<0.05). Conclusions: We for the first time demonstrated that PD-L1 and SOCS3 were independent prognostic factor for HCC patients. Co-expression of low PD-L1 and high SOCS3 could be a better predictive marker for HCC patients.

SUBMITTER: Chen L

PROVIDER: S-EPMC7391185 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients.

Chen Liuxi L Huang Xingxing X Zhang Wenzheng W Liu Ying Y Chen Bi B Xiang Yu Y Zhang Ruonan R Zhang Mingming M Feng Jiao J Liu Shuiping S Duan Ting T Chen Xiaying X Wang Wengang W Pan Ting T Yan Lili L Jin Ting T Li Guohua G Li Yongqiang Y Xie Tian T Sui Xinbing X

Journal of Cancer 20200711 18

Purpose: To investigate the correlation between the expression of PD-L1, SOCS3 and immune-related biomarkers CD276, CD4, CD8 in hepatocellular carcinoma (HCC) and further determine the relationship with clinicopathologic characteristics and the prognostic value of their co-expression in HCC patients. Methods: We assessed the expression of PD-L1, CD276, SOCS3, CD4 and CD8 by immunohistochemistry in tumor tissue from 74 HCC patients who underwent curative hepatectomy. Results: ...[more]

PMID: 32742491

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Project description:ObjectiveTo investigate the correlation between the expression of PD-L1 and HIF-1α in hepatocellular carcinoma (HCC) tissue and further analyze the association with clinical parameters and the prognostic value of coexpression in HCC patients.MethodsWe assessed the expression of PD-L1 and HIF-1α by immunohistochemistry in tumor tissue from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients.ResultsPD-L1 and HIF-1α exhibited in tumor tissue high expression rates of 41.11% (37/90) and 43.33% (43/90), respectively, and their expressions were positively correlated (r = 0.563, P < .01). High expression of PD-L1 was significantly associated with low albumin levels (P < .05); high expression of HIF-1α was significantly correlated with high alpha-fetoprotein (AFP) levels and low albumin levels (P < .05); high expression of both PD-L1 and HIF-1α was also significantly associated with high AFP levels and low albumin levels (P < .05). High expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1 α was respectively significantly associated with worse overall survival (OS) and disease-free survival (DFS) (P < .05). Patients with co-overexpression of PD-L1 and HIF-1α had the worst prognosis compared with other groups. Additionally, multivariate Cox regression models suggested that high expression of PD-L1, HIF-1α, as well as both PD-L1 and HIF-1α was an independent prognostic factor for OS and DFS (P < .05). Furthermore, the positive correlation and prognostic values of PD-L1 and HIF-1α were validated in an independent data set.ConclusionWe demonstrated that HCC patients with co-overexpression of PD-L1 and HIF-1α in tumor tissue had a significantly higher risk of recurrence or metastasis and death compared with others. Therefore, more frequent follow-up is needed for patients with co-overexpression of PD-L1 and HIF-1α. At the same time, a combinational therapy with HIF-1α inhibitors in conjunction with PD-L1 blockade may be beneficial for HCC patients with co-overexpression in the future.

Project description:ObjectivesAnti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti-PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti-PD-1/PD-L1 immunotherapy-related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti-PD-1/PD-L1 treatment in early-stage SqCLC.MethodsA total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens.ResultsThe prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes.ConclusionsEvaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.

Project description:The purpose of this study was to explore the effectiveness of radiomics based on multisequence MRI in predicting the expression of PD-1/PD-L1 in hepatocellular carcinoma (HCC). One hundred and eight patients with HCC who underwent contrast-enhanced MRI 2 weeks before surgical resection were enrolled in this retrospective study. Corresponding paraffin sections were collected for immunohistochemistry to detect the expression of PD-1 and PD-L1. All patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate analyses were used to select potential clinical characteristics related to PD-1 and PD-L1 expression. Radiomics features were extracted from the axial fat-suppression T2-weighted imaging (FS-T2WI) images and the arterial phase and portal venous phase images from the axial dynamic contrast-enhanced MRI, and the corresponding feature sets were generated. The least absolute shrinkage and selection operator (LASSO) was used to select the optimal radiomics features for analysis. Logistic regression analysis was performed to construct single-sequence and multisequence radiomics and radiomic-clinical models. The predictive performance was judged by the area under the receiver operating characteristic curve (AUC) in the training and validation cohorts. In the whole cohort, PD-1 expression was positive in 43 patients, and PD-L1 expression was positive in 34 patients. The presence of satellite nodules served as an independent predictor of PD-L1 expression. The AUC values of the FS-T2WI, arterial phase, portal venous phase and multisequence models in predicting the expression of PD-1 were 0.696, 0.843, 0.863, and 0.946 in the training group and 0.669, 0.792, 0.800 and 0.815 in the validation group, respectively. The AUC values of the FS-T2WI, arterial phase, portal venous phase, multisequence and radiomic-clinical models in predicting PD-L1 expression were 0.731, 0.800, 0.800, 0.831 and 0.898 in the training group and 0.621, 0.743, 0.771, 0.810 and 0.779 in the validation group, respectively. The combined models showed better predictive performance. The results of this study suggest that a radiomics model based on multisequence MRI has the potential to predict the preoperative expression of PD-1 and PD-L1 in HCC, which could become an imaging biomarker for immune checkpoint inhibitor (ICI)-based treatment.

Dataset Information

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients.

Publications

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients.

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