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.

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 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 CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Early Stage ◽  
Human Tumor ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

Algorithm for blood-based panel of methylated DNA and protein markers to detect early-stage hepatocellular carcinoma with high specificity.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4577-4577 ◽  
Author(s):  
Naga P. Chalasani ◽  
Abhik Bhattacharya ◽  
Adam Book ◽  
Brenda Neis ◽  
Kong Xiong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Disease ◽  
Early Stage ◽  
Lasso Regression ◽  
Protein Markers ◽  
Disease Etiology ◽  
Methylated Dna ◽  
Risk Patients ◽  
Higher Sensitivity

4577 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Though biannual ultrasound surveillance with or without alpha-fetoprotein (AFP) testing is recommended for at-risk patients, its sensitivity for early-stage HCC detection is suboptimal. We therefore evaluated performance of a biomarker panel incorporating methylated DNA markers (MDMs) and proteins for early HCC detection in at-risk patients with chronic liver disease. Methods: In an international, multicenter, case-control study, blood specimens were collected from patients with HCC per AASLD criteria and controls matched for age and liver disease etiology. All patients had underlying cirrhosis or chronic HBV infection. Whole blood was collected in cell-free DNA stabilizing and serum-separation tubes and shipped to a central laboratory for processing. The levels of 5 MDMs, AFP, and AFP-L3 were assessed along with age and sex. We used 537 samples in a 5-fold validation for developing a LASSO regression algorithm to classify samples as HCC positive or negative. Model robustness was tested by perturbing the data in silico and analyzing results with the predictive algorithm. Algorithm performance was compared to AFP alone and the GALAD score (Gender, Age, AFP-L3, AFP, and DCP). Results: The study included 136 HCC cases (81 early-stage—BCLC stage 0/A) and 401 controls. With specificity set at 89%, we developed a model using sex, AFP, and 3 MDMs (HOXA1, TSPYL5, B3GALT6) with higher sensitivity (70%) for early-stage HCC compared to GALAD (54%) or AFP (31% at 20 ng/mL or 52% at ≥7.7 ng/mL) (Table). The AUC for the HCC marker panel was 0.91 (95% CI 0.89 – 0.94) compared to GALAD (0.88; 95% CI 0.85 – 0.91) or AFP (0.84; 95% CI 0.81 – 0.87). The panel performed similarly in viral (AUC = 0.94) and non-viral (AUC = 0.89) etiologies. Conclusions: The robust algorithm based on novel blood-based biomarkers presented here provides higher sensitivity for early-stage HCC compared to other available blood-based biomarkers and, therefore, could significantly impact HCC clinical management and patient outcomes. Further clinical studies to validate the algorithm are ongoing. Clinical trial information: NCT03628651 . [Table: see text]

scholarly journals Hepatocellular Carcinoma in a Large Canadian Urban Centre: Stage at Treatment and Its Potential Determinants

2014 ◽  
Vol 28 (3) ◽  
pp. 150-154 ◽  
Author(s):  
Korosh Khalili ◽  
Ravi Menezes ◽  
Leyla Kochak Yazdi ◽  
Hyun-Jung Jang ◽  
Tae Kyoung Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analyses ◽  
Early Stage ◽  
Staging System ◽  
Milan Criteria ◽  
Tumour Stage ◽  
Urban Centre ◽  
Significant Difference ◽  
Treatment Centre ◽  
Bclc Staging

OBJECTIVE: To determine whether there is a significant difference in tumour stage between patients initially found with hepatocellular carcinoma (HCC) at a tertiary hepatobiliary centre and patients referred with tumours detected elsewhere; and to determine variables associated with referral in a palliative stage.METHODS: A retrospective review of 12,199 patients seen at a liver clinic over a 10.5-year period revealed 236 patients with HCC first detected internally (internal) and 163 who were referred with a known mass (referred). All patients were staged at the time of treatment using the Milan criteria for transplantation and Barcelona Clinic Liver Cancer (BCLC) staging system. Curative disease was defined as BCLC stages 0 and A. In the referred group, univariate and multivariate analyses were used to determine which of the following factors were significantly associated with presentation in a palliative stage: age, sex, ethnicity, cause of liver disease, presence of cirrhosis, location of residence and quintile of neighbourhood income.RESULTS: In comparing the internal versus referred patients, significant differences were found in the proportion of patients fulfilling Milan criteria (72% versus 36%), those with curative disease (75% versus 49%) and those with very early stage tumour (BCLC stage 0, 23% versus 7%); all differences were statistically significant (P<0.001). In patients referred for treatment of HCC from an outside institution, none of the variables tested were associated with presentation in a palliative stage.CONCLUSION: Patients with HCC referred to a liver treatment centre were more likely to be in palliative stages than those whose tumour was detected internally.

scholarly journals MACC1 as a Prognostic Biomarker for Early-Stage and AFP-Normal Hepatocellular Carcinoma

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64235 ◽  
Author(s):  
Chan Xie ◽  
Jueheng Wu ◽  
Jingping Yun ◽  
Jiaming Lai ◽  
Yunfei Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Early Stage

scholarly journals Prognostic Impact of AHNAK2 Expression in Patients Treated with Radical Cystectomy

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1748
Author(s):  
Dai Koguchi ◽  
Kazumasa Matsumoto ◽  
Yuriko Shimizu ◽  
Momoko Kobayashi ◽  
Shuhei Hirano ◽  
...  
Keyword(s):  
Radical Cystectomy ◽  
Prognostic Biomarker ◽  
Expression Patterns ◽  
Prognostic Impact ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
Independent Risk Factors

Data regarding expression levels of AHNAK2 in bladder cancer (BCa) have been very scarce. We retrospectively reviewed clinical data including clinicopathological features in 120 patients who underwent radical cystectomy (RC) for BCa. The expression levels of AHNAK2 in the specimens obtained by RC were classified as low expression (LE) or high expression (HE) by immunohistochemical staining. Statistical analyses were performed to compare associations between the two AHNAK2 expression patterns and the prognoses in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). A Kaplan–Meier analysis showed that patients with HE had a significantly worse RFS and CSS than those with LE (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.02–2.98, p = 0.027 and HR: 1.91, 95% CI: 1.08–3.38, p = 0.023, respectively). In a multivariate analysis, independent risk factors for worse RFS and CSS were shown as HE (HR: 1.96, 95% CI: 1.08–3.53, p = 0.026 and HR: 2.22, 95% CI: 1.14–4.31, p = 0.019, respectively) and lymph node metastasis (HR: 2.04, 95% CI: 1.09–3.84, p = 0.026 and HR: 1.19, 95% CI: 1.25–4.97, p = 0.009, respectively). The present study showed that AHNAK2 acts as a novel prognostic biomarker in patients with RC for BCa.

Metastasis-related miR-185 is a potential prognostic biomarker for hepatocellular carcinoma in early stage

2013 ◽  
Vol 67 (5) ◽  
pp. 393-398 ◽  
Author(s):  
Qiaoming Zhi ◽  
Junjie Zhu ◽  
Xiaobo Guo ◽  
Songbing He ◽  
Xiaofeng Xue ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarker ◽  
Early Stage

scholarly journals Effectiveness and tolerability of radiotherapy for patients with indolent non-Hodgkin’s lymphoma: a monocenter analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
I. Hadi ◽  
A. Schummer ◽  
M. Dreyling ◽  
C. Eze ◽  
R. Bodensohn ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin’S Lymphoma ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Rank Test ◽  
Prognostic Impact ◽  
Non Hodgkin’S Lymphoma ◽  
Kaplan Meier ◽  
Non Hodgkin's Lymphoma ◽  
Acute Side Effects

AbstractTo analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin’s lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan–Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87 months (95% CI 72–102 months). Median single dose per fraction was 2.0 Gy (range 1.5–2 Gy) and median total dose was 30.6 Gy (range 16–45 Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0 years (95% CI 8.3–19.7 years). The estimated PFS after 5 and 10 years were 73.0% and 65.5% in Kaplan–Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60 years old) had significantly superior PFS to those older than 60 years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0 Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I–II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I–II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6 months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I–II side effects recovered 3 to 6 months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19–137).

Sign in / Sign up

Export Citation Format

Share Document