scholarly journals PD-L1+NEUT, Foxp3+Treg, and NLR as New Prognostic Marker with Low Survival Benefits Value in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110458
Author(s):  
Lin Zhou ◽  
Jing Wang ◽  
Shao-cheng Lyu ◽  
Li-chao Pan ◽  
Xian-jie Shi ◽  
...  

Background: This presented study was aimed to evaluate the diagnostic and prognostic value of PD-L1+Neutrophils (PD-L1+NEUT) and neutrophil to lymphocyte ratio (NLR) based on our previous experience of Foxp3+Treg in transplantation. Methods: the NLR cutoff value of 1.79 was used to include 136 cases from the 204 patients with hepatocellular carcinoma (HCC) confirmed by clinical pathology, which were divided into highly-moderately and poorly differentiated HCC groups. The expressions of PD-L1+NEUT and Foxp3+Treg in peripheral blood and cancer tissue were detected with flow cytometry, meanwhile, PD-L1 and Foxp3 expressed in carcinoma and para-carcinoma tissues were marked by immunohistochemistry. Survival rates, including overall survival and disease-free survival, were calculated by the Kaplan–Meier curve and evaluated with the log-rank test. Finally, Cox risk regression model was used to analyze the independent risk factors for prognostic survival. Results: The level of PD-L1+NEUT, Foxp3+Treg, and NLR in peripheral blood of patients with poorly differentiated HCC were significantly increased (all P < .001). Both PD-L1+NEUT and NLR were positively correlated with Foxp3+Treg ( r = 0.479, P = .0017; r = 0.58, P < .0001). The level of PD-L1+NEUT and Foxp3+Treg as well as PD-L1 and Foxp3 in cancer tissue and patients with poorly differentiated HCC were obviously increased (all P < .01), respectively. Cox regression analysis indicated that PD-L1+NEUT, NLR, and Foxp3+Treg were independent risk factors for the prognosis ( P = .000, .000, .006) with a RR and 95%CI of 2.704-(2.155-3.393), 3.139-(2.361-4.173), 1.409-(1.105-1.798), respectively. Conclusion: PD-L1+NEUT, NLR, and Foxp3+Treg are independent risk factors for prognosis which maybe new marker of lower survival benefits.

Author(s):  
Yan Haixi ◽  
Chen Shuaishuai ◽  
Yang Qiong ◽  
Cai Linling

Objective: This study aims to evaluate the clinical application of preoperative prealbumin-to-fibrinogen ratio (PFR) in the clinical diagnosis and prognostic value of hepatocellular carcinoma (HCC) patients. Methods: The clinical and laboratory data of 269 HCC patients undergoing surgical treatment from January 2012 to January 2017 in Taizhou Hospital were retrospectively analyzed. The Cox regression model was used to analyze the correlation between PFR and other clinicopathologic factors in overall survival (OS) and disease-free survival (DFS). Results: Cox regression analysis showed that PFR (hazard ratios [HR] = 2.123; 95% confidence interval [95% CI], 1.271–3.547; P = 0.004)was independent risk factors affecting the OS of HCC patients. Furthermore, a nomogram was built based on these risk factors. The C indices statistics for the OS nomogram was 0.715. Conclusion: Nomograms based on PFR can be recommended as the correct and actual model to evaluate prognosis for patients with HCC.


2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Qinping Guo ◽  
Yinquan Wang ◽  
Jie An ◽  
Siben Wang ◽  
Xiushan Dong ◽  
...  

Background: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). Methods: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. Results: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. Conclusion: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.


2021 ◽  
Author(s):  
Xinxin Chen ◽  
Wenxia Qiu ◽  
Xuekun Xie ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
...  

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.


2021 ◽  
Author(s):  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
I-Cheng Lu ◽  
...  

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


2021 ◽  
pp. 000313482110415
Author(s):  
Naruhiko Honmyo ◽  
Tsuyoshi Kobayashi ◽  
Shintaro Kuroda ◽  
Kentaro Ide ◽  
Masahiro Ohira ◽  
...  

Background Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. Methods This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. Results Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). Discussion The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2776 ◽  
Author(s):  
Gian Paolo Caviglia ◽  
Michela Ciruolo ◽  
Antonella Olivero ◽  
Patrizia Carucci ◽  
Emanuela Rolle ◽  
...  

Keratin 19 (K19) is a cancer stem cell marker expressed by a subpopulation of hepatocellular carcinoma (HCC), associated with tumor aggressiveness. We evaluated the prognostic value of serum K19 fragment (CYFRA 21-1), in comparison or in combination with alpha-fetoprotein (AFP) and protein induced by vitamin-K absence or antagonist-II (PIVKA-II), in patients with HCC. A total of 160 patients (28F/132M; median age 62, range 44–86 years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were analyzed retrospectively. Median overall survival (OS) after HCC diagnosis was 35.1, 95% CI 27.1–70.5 months. Multivariate Cox regression analysis showed that CYFRA 21-1 > 2.7 ng/mL (hazard ratio (HR) = 3.39, p < 0.001), AFP > 20 ng/mL (HR = 2.27, p = 0.007), and PIVKA-II > 200 mAU/mL (HR = 2.17, p = 0.020) were independent predictors of OS. The combination of biomarkers positivity allowed us to stratify patients with HCC into four risk categories associated with a progressively lower survival probability (log-rank test, p < 0.001). CYFRA 21-1 resulted an independent prognostic factor of patients with HCC and its combination with AFP and PIVKA-II might be useful to tailor personalized treatment strategies.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 525-525
Author(s):  
C. M. Dumontet ◽  
J. C. Reed ◽  
M. Krajewska ◽  
I. Treilleux ◽  
J. R. Mackey ◽  
...  

525 Background: BCIRG 001 (1,491 pts) demonstrated significant superiority of docetaxel/doxorubicin/cyclophosphamide (TAC) over fluorouracil/doxorubicin/cyclophosphamide (FAC) given as adjuvant therapy for N+ operable BC in terms of disease-free survival (DFS) and overall survival (OS) (Martin et al, N Eng J Med, 2005). This ancillary study was aimed to identify tumor-associated factors related to DFS and OS. Methods: Formalin-fixed primary tumors from pts in BCIRG 001 were analysed by immunohistochemistry. Protocol- specified assessment of histological grade (GR), tumor size (TS), estrogen (ER) and progesterone receptors (PR), lymph node status (LN), HER2, MUC1, Mib, p53, Bcl-2, Bax, Bcl-X, Bag-1, tubulin β isotypes II, III and IV, tau protein and detyrosinated a tubulin was performed. Parameters were scored as the percentage of positive cells and analysed as lower or greater than median values. The samples were randomly split into training (2/3) and validation (1/3) sets. Associations between selected parameters and DFS or OS were tested through univariate analyses using the Kaplan Meier method (log-rank test) on the training set. A backward stepwise Cox regression analysis was performed to identify the final model of prognostic factors on the training set. Multivariate analyses were applied to the validation set. Results: 1,350 samples were split into a training (n=906) and a validation (n=444) set. In univariate GR, TS, LN, ER and PR, Mib, tau protein and HER2 were correlated with DFS in both sets. In multivariate ER, PR, TS, LN, Mib (all p<0.01) and tau (p=0.043) were significantly associated with DFS in the training set. In univariate GR, TS, LN, ER and PR, Mib, MUC1, Bcl-2, tubulin III and IV and tau were correlated with OS in both sets, with a trend for p53. In multivariate ER, TS, LN, Mib, p53 (all p<0.01) and PR (p=0.028) were independently correlated with OS in the training set. Conclusions: These data suggest that tau and p53 are independent markers of DFS and OS, respectively, while Mib is correlated with both DFS and OS in pts receiving these forms of adjuvant chemotherapy for N+ BC. Complementary analyses will be presented. No significant financial relationships to disclose.


2015 ◽  
Vol 32 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Yuan-da Zhou ◽  
Hui-kai Li ◽  
Yun-long Cui ◽  
Ti Zhang ◽  
Qiang Li

Aims: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. Methods: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. Results: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). Conclusions: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery.


2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.


2020 ◽  
Author(s):  
Wenwen Yang ◽  
Shuxia Guo ◽  
Haixia Wang ◽  
Yu Li ◽  
Xianghui Zhang ◽  
...  

Abstract Background: Metabolic syndrome (MS) could promote the development of cardiovascular disease(CVD). The aim of this study was to examine the association of MS and its components with CVD among Kazakhs in Xinjiang. Methods: According to the geographical distribution of the minority populations in Xinjiang, we selected the representative prefecture (Yili). A total of 2,644 participants completed the baseline survey between April 2010 and December 2012. The follow-up survey was conducted from April 2016 to December 2016. Only 2,286 out of 2,644 participants were followed-up on, with a follow-up rate of 86.46%. Cox regression was used to evaluate the association of each component and the number of combinations of MS components on the development of CVD. Results: Multivariate Cox regression analysis showed that blood pressure (BP), waist circumference (WC), and triglycerides (TG) were independently associated with CVD. Participants with 1–5 MS components had an increased hazard ratio for developing CVD, from 1.82 to 8.59 (trend P<0.001), compared with those without any MS components. This trend persisted after adjusting for other general risk factors. The risk of developing CVD increased when TG and WC coexisted, or when TG/WC and BP coexisted. However, no significant interactions were found between BP , WC , and TG. Conclusions: BP , WC, and TG were independent risk factors for CVD in Kazakhs. In clinical practice, a more informative assessment may be obtained by taking into account the number of MS components.


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