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.

Efficacy trend of hepatic resection for hepatocellular carcinoma with large multinodular tumor or macrovascular invasion.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Jian-Hong Zhong ◽  
Le-Qun Li ◽  
Xin-Ping Ye ◽  
Yang Ke ◽  
Lin Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Hepatic Resection ◽  
Tertiary Care ◽  
Disease Free Survival ◽  
Recent Decade ◽  
Free Survival ◽  
Disease Free

427 Background: Official guidelines and retrospective studies have different view on the role of hepatic resection (HR) for patients with large (≥5 cm) multinodular (≥2) hepatocellular carcinoma (HCC) and those involving macrovascular invasion (MVI). We aim to evaluate the efficacy and its variation trend and the safety of HR for these patients in three tertiary care settings. Methods: A consecutive sample of 1,824 patients with Child-Pugh A liver function and large/multinodular HCC or involving MVI and who underwent initial HR were divided into four groups: large/multinodular HCC of the previous (2000-2004, n = 496) and recent five years (2005-2010, n = 765), involving MVI of the previous (n = 242) and recent five years (n = 321). Results: Among our patient sample, the hospital mortality was less than 5% and had a downward trend. Moreover, patients in recent five years have statistically significant longer survival time. Among patients with large/multinodular HCC, patients in recent five years showed a significantly better overall survival than those in previous five years at 1-year (92% vs. 84%), 3-year (69% vs. 61%), and 5-year (45% vs. 40%) (P = 0.004). Moreover, among patients involving MVI, overall survival in recent five years was significantly higher at 1-year (83% vs. 78%), 3-year (50% vs. 41%), and 5-year (25% vs. 17%) (P= 0.033). However, the disease-free survival of recent five years was only slightly higher than that of the previous five years in the two subgroups. Conclusions: HR offers good overall survival for patients with resectable large/multinodular HCC or those involving MVI and with preserved liver function. Outcomes have tended to improve in recent decade.

Prognostic Role of Estrogen Receptor Determination in Breast Cancer

1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recent Literature ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Role ◽  
Free Survival ◽  
The Difference ◽  
Disease Free ◽  
Actuarial Method

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.

Prognosis of hepatic failure with the albumin-bilirubin model for hepatocellular carcinoma after stereotactic body radiotherapy with and without transplant.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 384-384
Author(s):  
Shaakir Hasan ◽  
Alexander V. Kirichenko ◽  
Paul Renz ◽  
Vijay Kudithipudi ◽  
Molly Vincent ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatic Failure ◽  
Stereotactic Body Radiotherapy ◽  
Disease Free Survival ◽  
Median Dose ◽  
Free Survival ◽  
Prognostic Assessment ◽  
Disease Free

384 Background: The Albumin-Bilirubin (ALBI) model is a validated prognostic assessment of cirrhosis in hepatocellular carcinoma (HCC), stratifying patients to grades 1(ALBI-1), 2(ALBI-2), or 3(ALBI-3). We reported that ALBI distinguishes patients at higher risk for hepatic failure(HF) after stereotactic body radiotherapy (SBRT) within the Child Pugh(CP) A population. We now apply the ALBI model to both CP-A and CP-B patients after SBRT with or without orthotropic liver transplant (OLT), and assess its prognostic capability of overall survival (OS) and HF relative to the CP model. Methods: From 2009-2017, 68 patients with 81 HCC lesions and CP-A (45) or CP-B (23) cirrhosis completed SBRT in this IRB approved study. The median dose was 45 Gy (35 - 57 Gy) in 4-7 fractions. Initial ALBI and CP scores were measured against OS and progression of CP class, which was recorded every 3-4 months. Median follow-up = 18 months. Results: The median age = 62 and tumor size = 3.5 cm (1.1 Ð 11 cm). 26 patients were ALBI-1, 31 ALBI-2, and 11 ALBI-3 prior to SBRT. For all patients, 2-year local control was 96%. 1 and 2 year OS was 77% and 54%, disease free survival was 71% and 40%, and freedom from CP progression was 71% and 56%, respectively. OS was significantly different between ALBI-1, ALBI-2, and ALBI-3 patients (P = 0.01), as was progression of CP class (P<0.001). When stratified by initial CP class, there were no significant differences in survival or CP progression [Table 1]. In a subset of 37 CP-A and 15 CP-B without OLT, rates of progressive cirrhosis were better predicted by ALBI (P<0.001) than CP class (P=0.09). Conclusions: Compared to the CP model, the ALBI index more precisely predicted HF and OS in HCC patients for both early and intermediate cirrhosis. Its application may help better select candidates for OLT after SBRT, who may be at higher risk for HF than initially predicted. [Table: see text]

scholarly journals Prognostic factors and the role of pelvic lymphadenectomy in uterine leiomyosarcomas

2019 ◽  
Vol 7 ◽  
pp. 205031211985681
Author(s):  
Tounsi Nesrine ◽  
Zemni Ines ◽  
Nawel Abdelwahed ◽  
Ayadi Mohamed Ali ◽  
Boujelbene Nadia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Clinical Stage ◽  
Menopausal Status ◽  
Disease Free Survival ◽  
Pelvic Lymphadenectomy ◽  
Free Survival ◽  
Disease Free ◽  
Lymphovascular Space Invasion

Objectives: Leiomyosarcomas are relatively rare uterine smooth muscle tumors. Surgery is the most common therapy choice for uterine leiomyosarcomas. However, controversy exists over the appropriate initial surgical management, especially about the role of lymph node sampling. The aim of our study is to analyze the prognostic factors and the role of lymphadenectomy in overall survival and in disease-free survival. Methods: We analyzed retrospectively 31 patients suffering from uterine leiomyosarcomas at Institute of Salah Azaiez during 2000–2014. Demographic and clinical features such as age, menopausal status, stage, tumor size, and management options were examined, and pathological characteristics such as mitotic count, lymphovascular space invasion, and tumor necrosis were evaluated. Results: Out of 31 patients treated for uterine leiomyosarcomas, pelvic lymphadenectomy was done for 18 patients. No para-aortic lymphadenectomy was performed. Median number of resected lymph nodes was 13 ± 7 (range: 3–27). Lymphatic metastasis was observed in 2 out of 18 patients with clinical stage IA and IIIB. The distribution of different variables (age, International Federation of Gynecology and Obstetrics stage, tumor size, mitotic count, and adjuvant treatment) between the group of patients, who had or had not lymphadenectomy done, had no significant difference. The 5-year overall survival and disease-free survival were 61% and 50%, respectively. Clinical stage, presence of lymphovascular space invasion, and lymph nodal dissection were found to be relevant for disease-free survival on univariate analysis. Only age and menopausal status were found to be a prognostic factor for overall survival. Conclusion: Hence, routine lymph node dissection was not generally recommended. Our study demonstrates that lymphadenectomy has a statistically significant effect on disease-free survival but not on overall survival.

scholarly journals FAM83D is associated with gender, AJCC stage, overall survival and disease-free survival in hepatocellular carcinoma

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Xuling Liu ◽  
Hong Gao ◽  
Jie Zhang ◽  
Dongying Xue
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Sequence Similarity ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
High Expression ◽  
Mrna Levels ◽  
Free Survival ◽  
Ajcc Stage ◽  
Disease Free

AbstractPrognostic significance of family with sequence similarity 83, member D (FAM83D) in hepatocellular carcinoma (HCC) patients has not been well-investigated using Gene Expression Omnibus (GEO) series and TCGA database, we compared FAM83D expression levels between tumor and adjacent tissues, and correlated FAM83D in tumors with outcomes and clinico-pathological features in HCC patients. Validated in GSE33006, GSE45436, GSE84402 and TCGA, FAM83D was significantly overexpressed in tumor tissues than that in adjacent tissues (all P<0.01). FAM83D up-regulation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in HCC patients (Log rank P=0.00583 and P=4.178E-04, respectively). Cox analysis revealed that FAM83D high expression was significantly associated with OS in HCC patients [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.005–2.063, P=0.047]. Additionally, patients deceased or recurred/progressed had significantly higher FAM83D mRNA levels than those living or disease-free (P=0.0011 and P=0.0238, respectively). FAM83D high expression group had significantly more male patients and advanced American Joint Committee on Cancer (AJCC) stage cases (P=0.048 and P=0.047, respectively). FAM83D mRNA were significantly overexpressed in male (P=0.0193). Compared with patients with AJCC stage I, those with AJCC stage II and stage III–IV had significantly higher FAM83D mRNA levels (P = 0.0346 and P=0.0045, respectively). In conclusion, overexpressed in tumors, FAM83D is associated with gender, AJCC stage, tumor recurrence and survival in HCC.

Role of adjuvant therapy in resected gallbladder cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 452-452
Author(s):  
Mohamed Abdelrahim Muddathir Hassan ◽  
Nicha Wongjarupong ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Fatima Hassan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Gallbladder Cancer ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients > 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p < 0.01), and stage III (HR 1.91 [1.35-2.70], p < 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.

scholarly journals Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Chongyang Ma ◽  
Tian Xu ◽  
Xiaoguang Sun ◽  
Shuang Zhang ◽  
Shuling Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Ppi Network ◽  
Free Survival ◽  
Disease Free

Liver cancer is the fourth leading cause of cancer death worldwide, and hepatocellular carcinoma (HCC) accounts for the greatest proportion of these deaths. Baicalein, a flavonoid isolated from the root of Scutellariae radix, is considered a potential candidate to treat HCC. However, the underlying molecular mechanisms remain poorly understood. In the present study, a network pharmacological approach was combined with microarray data (GSE95504) acquired from the Gene Expression Omnibus database to reveal the therapeutic mechanisms of action of baicalein at a systemic level. We identified 38 baicalein targets and 76 differently expressed genes (DEGs) following treatment with baicalein, including 55 upregulated and 21 downregulated genes. The DEGs were significantly enriched in the biological functions of apoptosis, endoplasmic reticulum stress, and PERK-mediated unfolded protein response. Protein-protein interaction (PPI) network construction and topological screening revealed a core module of PPIs including two baicalein targets, TP53 and CDK1, and two downregulated DEGs, HSPA1A and HSPA1B. Expression and survival data for these genes in the module derived from Gene Expression Profiling Interactive Analysis (GEPIA) were subjected to Kaplan–Meier analysis of overall survival and disease-free survival. Overexpression of CDK1, BRCA1, TUBB, HSPA1A, HSPA1B, and HSPA4 was associated with significantly worse overall survival, while overexpression of CDK1, CLU7, BRCA1, and TUBB was associated with significantly worse disease-free survival. These data suggest that baicalein exerts therapeutic effects against HCC via a PPI network involving TP53, CDK1, HSPA1A, and HSPA1B.

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 Indication of Liver Transplantation for Hepatocellular Carcinoma Should Be Reconsidered in Case of Microvascular Invasion and Multilocular Tumor Occurrence

2021 ◽  
Vol 10 (6) ◽  
pp. 1155
Author(s):  
Jan-Paul Gundlach ◽  
Stephan Schmidt ◽  
Alexander Bernsmeier ◽  
Rainer Günther ◽  
Victor Kataev ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Overall Survival ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Microvascular Invasion ◽  
Simultaneous Occurrence ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Disease Free

Liver transplantation (LT) is routinely performed for hepatocellular carcinoma (HCC) in cirrhosis without major vascular invasion. Although the adverse influence of microvascular invasion is recognized, its occurrence does not contraindicate LT. We retrospectively analyzed in our LT cohort the significance of microvascular invasion on survival and demonstrate bridging procedures. At our hospital, 346 patients were diagnosed with HCC, 171 patients were evaluated for LT, and 153 were listed at Eurotransplant during a period of 11 years. Among these, 112 patients received LT and were included in this study. Overall survival after 1, 3 and 5 years was 86.3%, 73.9%, and 67.9%, respectively. Microvascular invasion led to significantly reduced overall (p = 0.030) and disease-free survival (p = 0.002). Five-year disease-free survival with microvascular invasion was 10.5%. Multilocular tumor occurrence with simultaneous microvascular invasion revealed the worst prognosis. In our LT cohort, predominant bridging treatment was transarterial chemoembolization (TACE) and the number of TACE significantly correlated with poorer overall survival after LT (p = 0.028), which was confirmed in multiple Cox regression analysis for overall and disease-free survival (p = 0.015 and p = 0.011). Microvascular tumor invasion is significantly associated with reduced prognosis after LT, which is aggravated by simultaneous occurrence of multiple lesions. Therefore, indication strategies for LT should be reconsidered.

scholarly journals The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Guang Zhu ◽  
Ying Liu ◽  
Lei Zhao ◽  
Zhenhua Lin ◽  
Yingshi Piao
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Cancer Patients ◽  
Human Cancer ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cancer Type ◽  
Free Survival ◽  
Cancer Types ◽  
Disease Free

Sine Oculis Homeobox Homolog 1 (SIX1) is reported to promote cancer initiation and progression in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between SIX1 and cancer patients’ prognosis has not yet been systematically evaluated. Therefore, we performed a systematic review and meta-analysis in various human cancer types and extracted some data from TCGA datasets for further verification and perfection. We constructed 27 studies and estimated the association between SIX1 expression in various cancer patients’ overall survival and verified with TCGA datasets. Twenty-seven studies with 4899 patients are include in the analysis of overall, and disease-free survival, most of them were retrospective. The pooled hazard ratios (HRs) for overall and disease-free survival in high SIX1 expression patients were 1.54 (95% CI: 1.32-1.80, P&lt;0.00001) and 1.83 (95% CI: 1.31-2.55, P=0.0004) respectively. On subgroup analysis classified in cancer type, high SIX1 expression was associated with poor overall survival in patients with hepatocellular carcinoma (HR 1.50; 95% CI: 1.17-1.93, P =0.001), breast cancer (HR 1.31; 95% CI: 1.10-1.55, P =0.002) and esophageal squamous cell carcinoma (HR 1.89; 95% CI: 1.42-2.52, P&lt;0.0001). Next, we utilized TCGA online datasets, and the consistent results were verified in various cancer types. SIX1 expression indicated its potential to serve as a cancer biomarker and deliver prognostic information in various cancer patients. More works still need to improve the understandings of SIX1 expression and prognosis in different cancer types.

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