Prognostic value of plasma hPG80 (circulating progastrin), alone or in combination with Alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3033-3033
Author(s):  
Alexandre Prieur ◽  
Eric Assenat ◽  
Marie Dupuy ◽  
Sarah Iltache ◽  
Berengere Vire ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Early Stage ◽  
Alpha Fetoprotein ◽  
P Value ◽  
Prognostic Impact ◽  
Full Cohort ◽  
Early Stages ◽  
Systemic Treatments ◽  
Worse Prognosis

3033 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis since it is expressed in the advanced stages of the disease. Consequently, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages of the disease. hPG80 (circulating progastrin), a new drug target for cancer treatment which plays a pivotal role in tumorigenesis, is present in the blood of multiple types of cancers at early stages including HCC. The purpose of this study was to evaluate the prognostic value of plasma hPG80 in patients with HCC, in combination or not with AFP. Methods: A total of 168 HCC patients (BCLC from 0 to D) managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG80 was quantified using DxPG80 Lab kit (ECS-Progastrin) and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. Results: The median overall survival (OS) of the full cohort is 20.9 months. HCC patients with high hPG80 levels (hPG80+: >4.5 pM, 105/168) had significantly lower median OS compared to patients with low hPG80 levels (hPG80-: <4.5 pM, 63/168) (12.4 months versus undefined respectively, p < 0.0001). Patients with high AFP (AFP+: >100 ng/mL, 69/165) had significantly lower median OS compared to patients with low AFP (AFP: <100 ng/mL 96/165) (7.2 months versus undefined, p < 0.0001). To improve the stratification, the patients were further categorized into four groups: hPG80-/AFP- (n = 42), hPG80+/AFP- (n = 54), hPG80-/AFP+ (n = 21) and hPG80+/AFP+ (n = 48). In the AFP- group, hPG80+ patients exhibited a significantly worse prognosis than those with hPG80- (26.3 months versus undefined, p=0.0087). Similarly, in the AFP+ group, patients with hPG80+ had a significantly worse survival compared to hPG80- patients (5.7 months versus 13.4 months, p = 0.0391). Finally, we evaluated the median OS of AFP+ patients according to BCLC staging. Interestingly, in the group BCLC 0 to B, hPG80+ had a significantly worse prognosis than those with hPG80- (15.8 months versus 40.25 months, p=0.0317). Conclusions: Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and worst prognosis, especially for those patients with negative AFP and early-stage HCC.

scholarly journals Circulating MicroRNA-21 As A Novel Noninvasive Biomarker for Hepatocellular Carcinoma Compared with Alpha Fetoprotein Gold Test

2021 ◽  
Author(s):  
Asmaa Gamal Osman ◽  
Khalid Shaaban Hashem ◽  
Laila Mohamed Youssef ◽  
Ahmed Nabil
Keyword(s):  
Hepatocellular Carcinoma ◽  
Standard Test ◽  
Alpha Fetoprotein ◽  
Control Group ◽  
P Value ◽  
Circulating Microrna ◽  
Liver Imaging ◽  
Diagnostic Strategies ◽  
Early Stages ◽  
Significant Difference

Hepatocellular carcinoma (HCC) is the greatest traditional kind of pre-eminent cancer worldwide, which happens mainly in chronic liver disease and cirrhotic patients. The available surveillance strategies for suspected HCC patients include serum alpha-fetoprotein (AFP) and liver imaging have been mainly recommended. However, the sensitivity and selectivity of these diagnostic strategies especially in the early stages of HCC have many obstacles. MicroRNAs (miRNAs) are non-coding RNAs that are 18–25 nucleotides in length. Plasma miRNAs may be a promising new biomarker for cancer detection and prognosis in the early stages. Assessment of Plasma MicroRNA-21 (miRNA-21) significance as a noninvasive Hepatocellular carcinoma marker compared with AFP gold standard test to improve HCC early diagnostic power. This is a prospective research project that included 90 patients in total, split into three classes., liver cirrhosis patients (LC) without any malignancies and (HCC) patients in addition to the healthy control group. Patients and controls were subjected to the clinical studies, routine investigations, imaging studies, and detection of plasma miRNA-21 & AFP. miRNA-21 showed a highly significant difference in the 3 studied groups. Control group with LC group, control group with HCC group, and LC group with HCC group P value (P 0.0001, P1 0.0001, P2 0.0001and P3 0.0001) respectively. Also, a highly significant difference was observed between pre-TACE and post-TACE miRNA-21 in the HCC group P value (0.0001). Circulating miRNA-21 may be used as a noninvasive co biomarker with AFP to increase HCC diagnostic accuracy in its early stages.

scholarly journals Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 402
Author(s):  
Marie Dupuy ◽  
Sarah Iltache ◽  
Benjamin Rivière ◽  
Alexandre Prieur ◽  
George Philippe Pageaux ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Median Overall Survival ◽  
Prognostic Biomarker ◽  
Early Stage ◽  
Prognostic Impact ◽  
Rank Tests ◽  
Early Stages ◽  
Kaplan Meier ◽  
Bclc Staging ◽  
Higher Sensitivity

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

scholarly journals The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Early Stage ◽  
Group Iii ◽  
Real Time Quantitative Pcr ◽  
Early Stages ◽  
Group I ◽  
Egyptian Patients ◽  
Cirrhotic Patients

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

scholarly journals Role of SIRT-3, p-mTOR and HIF-1α in Hepatocellular Carcinoma Patients Affected by Metabolic Dysfunctions and in Chronic Treatment with Metformin

2019 ◽  
Vol 20 (6) ◽  
pp. 1503 ◽  
Author(s):  
Serena De Matteis ◽  
Emanuela Scarpi ◽  
Anna Granato ◽  
Umberto Vespasiani-Gentilucci ◽  
Giuliano La Barba ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Significant Benefit ◽  
Diabetic Patients ◽  
Advanced Stage ◽  
Metabolic Dysfunctions ◽  
Worse Prognosis

The incidence of hepatocellular carcinoma deriving from metabolic dysfunctions has increased in the last years. Sirtuin- (SIRT-3), phospho-mammalian target of rapamycin (p-mTOR) and hypoxia-inducible factor- (HIF-1α) are involved in metabolism and cancer. However, their role in hepatocellular carcinoma (HCC) metabolism, drug resistance and progression remains unclear. This study aimed to better clarify the biological and clinical function of these markers in HCC patients, in relation to the presence of metabolic alterations, metformin therapy and clinical outcome. A total of 70 HCC patients were enrolled: 48 and 22 of whom were in early stage and advanced stage, respectively. The expression levels of the three markers were assessed by immunohistochemistry and summarized using descriptive statistics. SIRT-3 expression was higher in diabetic than non-diabetic patients, and in metformin-treated than insulin-treated patients. Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Moreover, our results describe a slight, albeit not significant, benefit of high SIRT-3 and a significant benefit of high nuclear HIF-1α expression in early-stage patients, whereas high levels of p-mTOR correlated with worse prognosis in advanced-stage patients. Our study highlighted the involvement of SIRT-3 and p-mTOR in metabolic dysfunctions that occur in HCC patients, and suggested SIRT-3 and HIF-1α as predictors of prognosis in early-stage HCC patients, and p-mTOR as target for the treatment of advanced-stage HCC.

scholarly journals The Real Impact of Bridging or Downstaging on Survival Outcomes after Liver Transplantation for Hepatocellular Carcinoma

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 721-733
Author(s):  
Sunyoung Lee ◽  
Kyoung Won Kim ◽  
Gi-Won Song ◽  
Jae Hyun Kwon ◽  
Shin Hwang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Early Stage ◽  
Organ Procurement ◽  
Survival Outcomes ◽  
Full Cohort ◽  
Donor Liver Transplantation ◽  
Positron Emission ◽  
The Impact

<b><i>Introduction:</i></b> There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. <b><i>Objective:</i></b> We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. <b><i>Methods:</i></b> This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. <b><i>Results:</i></b> The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all <i>p</i> ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (<i>p</i> = 0.070 and <i>p</i> = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all <i>p</i> &#x3c; 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, <i>p</i> = 0.001; HR: 1.72, <i>p</i> = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, <i>p</i> &#x3c; 0.001; HR: 3.31, <i>p</i> &#x3c; 0.001), and positron emission tomography positivity (HR: 2.57, <i>p</i> &#x3c; 0.001; HR: 2.57, <i>p</i> &#x3c; 0.001) were independent predictors for worse RFS and OS. <b><i>Conclusions:</i></b> The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.

scholarly journals Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Qing Yin ◽  
Chun-Hui Yuan ◽  
Zhen Qu ◽  
Qing Guan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Prognostic Significance ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Diagnostic Strategies ◽  
Systemic Treatments

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.

scholarly journals Are preoperative high soluble programmed death ligand 1 levels responsible for patients’ poor prognoses in hepato-biliary-pancreatic cancer?

2020 ◽  
Author(s):  
Rei Okada ◽  
Yuichiro Otsuka ◽  
Masaru Tsuchiya ◽  
Tetsuya Maeda ◽  
Jun Ishii ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pancreatic Cancer ◽  
Poor Prognosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prognostic Impact ◽  
Poor Overall Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Normal Albumin ◽  
Worse Prognosis

Abstract Background Several reports showed that high soluble programmed death-ligand 1(sPD-L1) level was a risk factor for poor prognosis in various tumors. To date, the clinicopathologic and prognostic impact of sPD-L1 level in patients with hepato-biliary-pancreatic cancer have not been determined. Methods A total of 119 patients (66 patients with hepatocellular carcinoma, 23 patients with cholangiocarcinoma, 30 patients with pancreatic cancer) who were treated at the Toho University Omori Hospital (Tokyo, Japan) from 2008 to 2016 were retrospectively analyzed. sPD-L1 levels were measured using an enzyme-linked immunosorbent assay for PD-L1 to evaluate clinicopathologic and prognostic impact. Results sPD-L1 levels were significantly higher in low-albumin group than normal albumin group. According to stages in hepatocellular carcinoma and cholangiocarcinoma, there were no significant differences in sPD-L1 levels, which gradually increased according to stage in pancreatic cancer. Using a cut-off value of 81.6 pg/ml for sPD-L1level, the high sPD-L1 group showed significantly worse prognosis than the low sPD-L1 group in patients with pancreatic cancer. Multivariate analysis identified sPD-L1 level ≥ 81.6 mg/dl (p = 0.047) as an independent predictor of poor overall survival in patients with pancreatic cancer. Conclusion High sPD-L1 levels were independently associated with poor prognosis. However, this association in hepatocellular carcinoma or cholangiocarcinoma was not clear.

Sign in / Sign up

Export Citation Format

Share Document