Higher tumor protein kinase D1 correlates with increased tumor size, BCLC stage, CA199 level, AFP level and worse overall survival in hepatocellular carcinoma patients

2020 ◽  
Author(s):  
Junchen Ge ◽  
Xu Zhang ◽  
Boyang Zhang ◽  
Li Zhu ◽  
Meng Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Protein Kinase ◽  
Tumor Size ◽  
Protein Kinase D1

scholarly journals Protein Kinase D1 Is Increased in Tumor Tissue, Correlates With Advanced Tumor Features and Worse Prognosis of Non-Small Cell Lung Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382093412
Author(s):  
Jing Yao ◽  
Yan Jiang ◽  
Shuang Geng ◽  
Li Sun
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Protein Kinase D1 ◽  
Disease Free

Objective: This study aimed to assess protein kinase D1 expression and its association with tumor characteristics as well as prognosis in patients with non-small cell lung cancer. Methods: Protein kinase D1 expression in tumor tissues and adjacent tissues from 172 patients with non-small cell lung cancer who underwent surgical resection were analyzed by immunohistochemical staining. Based on the total immunohistochemical score, protein kinase D1 expression was classified as protein kinase D1 high expression (further divided into protein kinase D1 high+++, protein kinase D1 high++, and protein kinase D1 high+ expressions) and protein kinase D1 low expression. Clinical characteristics of patients with non-small cell lung cancer were acquired from the database. Accumulating disease-free survival and overall survival were calculated based on patients’ relapse/survival status. Results: Protein kinase D1 expression was increased in tumor tissues compared to adjacent tissues ( P < .001). Tumor protein kinase D1 high expression correlated with poorer pathological differentiation ( P = .041), increased tumor size ( P = .003), the presence of lymph node metastasis ( P = .001), and elevated tumor, nodes and metastases stage ( P < .001). Besides, both accumulating disease-free survival and overall survival were decreased in patients with tumor protein kinase D1 high expression compared to patients with tumor protein kinase D1 low expression ( P = .010 for disease-free survival and P = 0.005 for overall survival). Moreover, they were lowest in patients with tumor protein kinase D1 high+++ expression, followed by patients with tumor protein kinase D1 high++ expression, then patients with tumor protein kinase D1 high+ expression, and highest in patients with tumor protein kinase D1 low expression ( P < .001 for disease-free survival and P = .001 for overall survival). Notably, higher tumor protein kinase D1 expression was an independent predictive factor for decreased disease-free survival ( P = .001) and overall survival ( P = .004). Conclusions: Protein kinase D1 might be a potential marker to identify patients with non-small cell lung cancer with worse tumor features and prognosis.

scholarly journals Identification of prognostic biomarkers and correlations with immune infiltrates among cGAS-STING in hepatocellular carcinoma

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Zhenhua Qi ◽  
Fang Yan ◽  
Dongtai Chen ◽  
Wei Xing ◽  
Qiang Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
T Cells ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Prognostic Biomarkers ◽  
Mitogen Activated Protein Kinase ◽  
Type I Interferons ◽  
Type I ◽  
Sting Pathway

Abstract The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway induces innate immunity by activating the production of inflammatory cytokines and type I interferons. Recently, studies revealed that self-DNA from by-products of chromosome instability and tumors could activate the cGAS-STING pathway, and subsequently promote or inhibit tumor development. However, the prognostic value and correlations with immune infiltrates of the cGAS-STING pathway in hepatocellular carcinoma (HCC) have not been clarified. In the present study, we used the Molecular Signatures Database, Oncomine, UALCAN, Human Protein Atlas, Kaplan–Meier plotter, LinkedOmics, and Tumor Immune Estimation Resource databases. Overexpression of XRCC5, IRF3, TRIM21, STAT6, DDX41, TBK1, XRCC6, TREX1, PRKDC, and TMEM173 was markedly correlated with clinical stages and pathological grades in HCC. Moreover, higher mRNA expression of XRCC5, XRCC6, and PRKDC was significantly related with shorter overall survival. However, higher mRNA expression of IFI16, STAT6, NLRC3, and TMEM173 was associated with favorable overall survival. Our results suggested that the kinase targets of the cGAS-STING pathway included the SRC family of tyrosine kinases (LCK and LYN), phosphoinositide 3-kinase-related protein kinase (PIKK) family kinases (ATM and ATR), and mitogen-activated protein kinase 1 (MAPK1). Furthermore, we identified significant correlations among the expression of cGAS-STING pathway and infiltration of B cells, CD4+T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC. The expression of the cGAS-STING pathway also exhibited strong relationships with diverse immune marker sets in HCC. These findings suggest that cGAS-STING pathway members may be used as prognostic biomarkers and immunotherapeutic targets HCC patients.

Abstract 4621: Downregulation of Protein Kinase D1 in hepatocellular carcinoma (HCC): Potential as a diagnostic/prognostic molecular marker

2010 ◽  
Author(s):  
Preethi Prakash ◽  
Matt Freiz ◽  
Teresa Bohlmeyer ◽  
Micheal R.D Koch ◽  
Subhash C. Chauhan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase ◽  
Molecular Marker ◽  
Protein Kinase D1

Prognostic Significance of Globulin/Low-Density Lipoprotein Ratio In Patients With Hepatocellular Carcinoma After Local Ablative Therapy

2021 ◽  
Author(s):  
Wenying Qiao ◽  
Qi Wang ◽  
Jianjun Li ◽  
Chunwang Yuan ◽  
Dandan Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Size ◽  
Low Density Lipoprotein ◽  
Prognostic Significance ◽  
Density Lipoprotein ◽  
Low Density ◽  
Operating Characteristics ◽  
Tumor Number ◽  
Receiver Operating

Abstract Background: Low-density lipoprotein (LDL) and globulin have been found to be predictors for some malignant tumors, but their predictive value in hepatocellular carcinoma (HCC) has hardly to be elucidated. This study assessed the prognostic significance of globulin to low-density lipoprotein ratio (GLR) in HCC patients before ablation.Materials and methods: This study analyzed 312 HCC patients hospitalized and underwent ablative treatment in Beijing You 'an Hospital, Capital Medical University, from January 1, 2012 to January 1, 2017. Cox regression analysis was used to assess the factors independently associated with recurrence and survival. The optimal cut-off value and prognostic role of GLR and other markers were evaluated via the receiver operating characteristic-ROC curves and the Youden index. Overall survival (OS) and recurrence-free survival (RFS) were calculated by Kaplan-Meier analysis, and compared between groups using the log-rank.Result: Univariate and multivariate analysis found that the tumor number (HR: 1.676;95%CI: 1.113-2.526), tumor size (HR: 1.967;95%CI: 1.251-3.092), GLR (HR: 1.028;95%CI: 1.004-1.052) were independent risk factors of relapse; while etiology (HR: 1.328;95%CI: 1.052-1.677), tumor number (HR: 1.615;95%CI: 1.015-2.570), tumor size (HR: 2.061; 95%CI: 1.243-3.418), Fib (HR: 0.73; 95%CI: 0.535-0.996) and GLR (HR: 1.031;95%CI: 1.003-1.06) were related to overall survival. We classified the patients into groups with high and low levels of GLR based on the optimal cut-off value of GLR identified by generating receiver operating characteristics (ROC) curve. The cumulative 1-, 3-, and 5-year RFS rates in the low GLR group were 76.4%, 53.8% and 43.4%, while those in the high GLR group were 71%, 31% and 22%, respectively (P <0.001). Concerning OS, the low GLR group showed a 1-, 3- and 5-year OS of 99.5%, 92.0% and 80.2% versus 98%, 73% and 63% for the high GLR group (P <0.001). Finally, patients were stratified by GLR and tumor size. The outcomes revealed that patients in group A (GLR<16.54 and tumor size ≤30mm) showed better prognosis than group B (GLR≥16.54 and tumor size≤30mm or GLR<16.54 and tumor size >30mm) and group C (GLR≥16.54 and tumor size >30mm) (P <0.001). Conclusions: Preoperative GLR ratio could serve as a biomarker to predict prognosis in HCC patients who underwent complete ablation.

scholarly journals Reclassification of tumor size for solitary HBV-related hepatocellular carcinoma by minimum p value method: a large retrospective study

2020 ◽  
Author(s):  
Hongzhi Liu ◽  
Yuan Yang ◽  
Chuanchun Chen ◽  
Lei Wang ◽  
Qizhen Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Cirrhosis ◽  
Tumor Size ◽  
Prognostic Significance ◽  
P Value ◽  
Tumor Differentiation ◽  
Clinicopathologic Characteristics ◽  
Large Retrospective Study

Abstract Background and Objectives Tumor size is one of the most important issues for hepatocellular carcinoma (HCC) treatment and prognosis but the classification of it still controversial. The aim of this study was to screen appropriate cutoffs for size of solitary HBV-related HCC. Methods A cohort of 1760 patients with solitary HBV-related HCC undergoing curative liver resection were divided into 11 groups based on tumor size in 1-cm intervals. The minimum p value method was used to screen the appropriate size cutoff according to overall survival (OS). Results There are 8 dichotomy, 8 trichotomy and 14 inquartation cutoffs were screened when classifying tumor sizes in accordance with OS. After reclassified patients into three new classifications: ≤ 3cm (n = 422), > 3 and ≤ 9cm (n = 1072), and > 9cm (n = 266). The comparison of clinicopathologic characteristics among these three classifications showed that the increase of tumor size was associated with the increase of α-fetoprotein (AFP), Microvascular invasion (MVI), tumor differentiation, and liver cirrhosis. And the comparison of the OS among three classifications showed statistical differences. Conclusions This study suggested that size criteria of 3cm and 9cm in solitary HBV-related HCC patients were appropriate based on biological characteristics and prognostic significance.

scholarly journals High Expression of PDZ-binding Kinase Is Correlated With Poor Prognosis and Immune Infiltrates in Hepatocellular Cacinoma

2021 ◽  
Author(s):  
Wei Mu ◽  
Yaoli Xie ◽  
Jinhu Li ◽  
Runzhi Yan ◽  
Jingxian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Protein Kinase ◽  
Receiver Operating Characteristic ◽  
Roc Curve ◽  
Poor Prognosis ◽  
Operating Characteristic ◽  
High Expression

Abstract BackgroundPDZ-binding kinase (PBK) encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. There is evidence that overexpression of this gene is associated with tumorigenesis. However, the role of PBK in hepatocellular carcinoma (HCC) remain unclear. Therefore, we evaluated the prognostic role of PBK and its correlation with immune infiltrates in Hepatocellular Carcinoma.MethodsThe expression of PBK in pan-cancers was studied by Onconmine and TIMER. The expression of PBK in HCC patients and its relationship with clinicopathological characteristics were analyzed using The Gene Expression Profiling Interactive Analysis (GEPIA), The human protein atlas database (HPA), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic value of PBK in HCC patients. The relationship between PBK and prognosis of HCC was performed by GEPIA and Kaplan Meier plotter web tool. The correlations between the clinical characteristics and overall survival were analyzed by Univariate Cox regression and Multivariate Cox hazards regression to identify possible prognostic factors for HCC patients. LinkedOmics was applied to investigate co-expression associated with PBK and to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The network map of PBK and related genes is constructed by GeneMANIA. Finally, TIMER and TISIDB were used to analyze the correlations between PBK and tumor-infiltrating immune cells.ResultsPBK was highly expressed in many types of tumors, including hepatocellular carcinoma, and was significantly related to tumor stage (P=0.0089), age (P=0.0131) and race (P=0.0024) of HCC patients. The receiver operating characteristic (ROC) curve analysis from 4 GEO databases showed that PBK is a predictive marker for HCC. Moreover, high expression of PBK correlated with poor prognosis. Multivariate Cox hazards regression showed that high expression of PBK may be an independent risk factor for overall survival in HCC patients (HR = 1.566, 95% CI=1.062-2.311, P= 0.024). The Protein–protein interaction network showed that PBK significantly interacted with LRRC47, ARAF, LGALS9B, TTK, MELK and other essential genes. Furthermore, enrichment analysis showed that PBK and co-expressed genes participated in many biological processes, cell composition, molecular functions and pathways in HCC. Finally, the immune infiltration analysis by TIMER and TISIDB indicated that PBK expression tightly correlated with the infiltration of tumor-infiltrating lymphocytes (TILs), chemokines, and receptors.ConclusionsHigh expression of PBK is significantly correlated with poor survival and immune infiltrates in hepatocellular carcinoma. Our study suggests that PBK can be used as a biomarker of poor prognosis and potential immune therapy target in hepatocellular carcinoma.

Importance of subset classification based on tumor size for patients with single hepatocellular carcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 373-373
Author(s):  
Jian-Hong Zhong ◽  
Bang-De Xiang ◽  
Liang Ma ◽  
Yan-Yan Wang ◽  
Ning-Fu Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Size ◽  
Staging System ◽  
Cancer Staging ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Similar Survival ◽  
Group 1

373 Background: Single hepatocellular carcinoma (HCC) regardless of size that without vascular invasion is classified as stage A disease in the Barcelona Clinic Liver Cancer staging system. However, patients with different tumor size may have different overall survival after hepatectomy. This study compared the prognosis of patients with single HCC after hepatectomy among groups with different tumor size. Methods: Patients with newly diagnosed single HCC from January 1, 2004 to October 31, 2013 were classified according to tumor size: group 1, ≤ 5 cm; group 2, > 5 cm and ≤ 8 cm; group 3, > 8 cm and < 10 cm; and group 4, ≥ 10 cm. Overall survival analysis was performed according to tumor size. Results: A total of 857 patients were enrolled. Among them, 814 (95.0%) were with Child-Pugh A class liver function. Blood loss was 367 ± 424 mL. Groups 1, 2, 3, and 4 consisted of 426 (49.7%), 229 (26.7%), 52 (6.1%), and 150 (17.5%) patients, respectively. The 5 years overall survival ranged from 35 to 63% in all four groups. The median survival time differed significantly according to tumor size (76, 49, 43, and 38 months in groups 1, 2, 3, and 4, respectively; P  <  0.001). Group 3 had overall similar survival to group 4. Multivariate analysis showed that group 3 and 4 had significantly worse overall survival compared to group 1 and 2. Conclusions: Patients in group 3 and 4 had significant worse prognosis than those in group 1 or group 2. Our results suggest that subset classification based on tumor size is warranted to patients’ prognosis.

Proline-Directed Protein Kinase FA Is a Powerful and Independent Prognostic Predictor for Progression and Patient Survival of Hepatocellular Carcinoma

2006 ◽  
Vol 24 (23) ◽  
pp. 3780-3788 ◽  
Author(s):  
Yu-Chen Hsu ◽  
Hsiao-Hui Fu ◽  
Yung-Ming Jeng ◽  
Po-Huang Lee ◽  
Shiaw-Der Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Protein Kinase ◽  
Patient Survival ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Prognostic Role ◽  
Free Survival ◽  
Disease Free

Purpose Molecular, cellular, and animal studies have established that overexpressed proline-directed protein kinase FA (PDPK FA) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK FA in cancer patients remains largely unknown. In this study, association of PDPK FA expression with poor prognosis of hepatocellular carcinoma (HCC) patients was examined. Patients and Methods PDPK FA expression in the resected tumors of 134 HCC patients (112 men and 22 women) with ages ranging from 33 to 83 years (mean, 55 years) was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK FA associated with tumor cells was used as the major scoring parameter for positive PDPK FA expression. Results Approximately 68% of the patients (91 of 134) exhibited positive PDPK FA expression. Patients with positive PDPK FA showed poorer disease-free survival and overall survival (P < .001). Cox multivariate regression analysis further established PDPK FA as the strongest independent prognosticator for progression and patient survival of HCC (hazard ratio [HR], 2.878; 95% CI, 1.634 to 5.067 for disease-free survival; and HR, 5.035; 95% CI, 2.137 to 11.866 for overall survival; P < .001). Conclusion Consistent with PDPK FA’s essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FA in progression and patient survival of surgically resected primary HCC. Taken together, PDPK FA represents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection.

scholarly journals Advanced radiotherapy technique in hepatocellular carcinoma with portal vein thrombosis: Feasibility and clinical outcomes

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257556
Author(s):  
Chonlakiet Khorprasert ◽  
Kanokphorn Thonglert ◽  
Petch Alisanant ◽  
Napapat Amornwichet
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiation Dose ◽  
Portal Vein ◽  
Tumor Size ◽  
Response Rate ◽  
Therapeutic Option ◽  
Overall Response ◽  
The Mean ◽  
Grade 3

Background In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single—institution. Objectives To examine clinical results in terms of overall survival (OS), local control (LC), response of primary tumor and PVTT, hepatic and gastrointestinal adverse reaction, and prognosis variables for OS and LC. Materials and methods Between July 2007 and August 2019, non-metastatic HCC with PVTT patients treated with RT were retrospectively reviewed and evaluated. Results The analysis included data from 160 patients. The mean age of the patients was 60.8 years ((95% CI 58.2–62.0). The median diameter of the tumor was 7.7 cm (range: 1–24.5). 85 (54.5%) individuals had PVTT in the main or first branch. At 1.8–10 Gy per fraction, the mean biologically effective dose (BED) as α/β ratio of 10 was 49.6 (95% CI 46.7–52.5) Gy10. The median survival time was 8.3 (95% CI 6.1–10.3) months. Survival rates at one and two years were 39.6% and 17.1%, respectively. Estimated incidence of local failure using competing risk analysis were 24% and 60% at 1 and 2 years, respectively. The overall response rate was 74%, with an 18.5 percent complete response rate. In multivariate analysis, tumor size, overall response, and radiation dose were all significant prognostic variables for OS. Hepatic unfavorable events of grade 3 and 4 were for 14.1% of the total. There was no occurrences of grade 3–4 gastrointestinal toxicity, either acute or late. Additionally, there were no treatment-related mortality. Conclusions Advanced RT is regarded as a safe and effective therapeutic option for HCC with PVTT. Overall survival was clearly related to tumor size, radiation dose, and tumor/PVTT response. Individuals with BED 56 Gy10 had significantly better overall survival than patients with BED 56 Gy10. A prospective randomized trial is required to validate these outcomes in order to corroborate these findings.

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