Diagnosis Of HCC Research Articles

The impact of previous local therapy (LT) on overall survival (OS) in patients with advanced hepatocellular carcinoma (aHCC) treated with atezolizumab/bevacizumab (A+B) as first line systemic therapy.

e16129 Background: Treatment options for aHCC have drastically improved over the past few years with immunotherapy at the forefront. Ongoing studies aim to identify the benefit of immunotherapy in combination with local therapies, but there are no studies that analyze the impact of previous local therapy on OS in patients who later receive A+B for treatment of aHCC. This study aims to analyze the impact of previous local therapy on OS in patients with aHCC treated with first line A+B within the Veterans Health Administration (VHA). Methods: Patients with aHCC receiving first line systemic therapy with A+B at VHA between Dec 1, 2019 through Mar 1, 2022 were identified from the electronic medical record (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR and followed the patients from the date of diagnosis, date of local treatment and date of A+ B initiation until death or their last VHA visit with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates and the Mann-Whitney test was used to compare medians. Results: 332 patients with aHCC received A+B. 67% of patients received prior LT. Patients who received LT had better ECOG status, Child-Pugh classification, and BCLC staging at time of diagnosis. There was no difference in age at diagnosis, race/ethnicity, ALBI score at time of diagnosis or at time of starting A+B, or presence of extrahepatic spread at time of starting A+B. There was a statistically significant difference in time from HCC diagnosis to start of A+B, with patients who received LT having a longer interval time. There was a small but not statistically significant difference in median OS from the start of A+B, favoring people who received LT. Conclusions: Our unique retrospective study confirms that patients receiving LT have better OS from the time of diagnosis. Disease biology and LT response may be contributing to this survival benefit. However, the OS was similar from the time of initiation of A+B in patients receiving LT versus patients who did not receive any LT.[Table: see text]

Patients' views on HCC biospecimen research: Understanding the role of race and culture through interviews.

HCC is a leading cause of cancer-related mortality; there are significant racial and ethnic disparities in HCC risk and survival. Our knowledge regarding whether molecular and genetic factors contribute to these observed differences is limited by scarcity of biospecimens, which are especially scarce in minority populations. Because biospecimens are not needed for HCC diagnosis or treatment, patients are less likely to provide biospecimens solely for research purposes. We identified participants, n = 32, from an ongoing prospective cohort study. Using semi-structured interviews, we examined perceptions of providing biospecimens for research to identify factors that motivate and hinder their willingness to donate. Directed content analysis resulted in 6 themes, including reported experiences of (1) support or suspicion in donating biospecimens; (2) desire to help others or themselves; (3) inconvenience, discomfort, and concerns about privacy or recovery as hindrances to donating; (4) recommendations for health care researchers; (5) preferences for biospecimen donation; and (6) the influence of race, culture, and religion in donating biospecimens. Patients reported being least willing to donate specimens that required more invasive procedures and recovery, namely, liver tissue. Patients reported being more likely to donate if the data collection was convenient, resulted from discarded tissue, or was instituted as part of a broad opt-in consent approach, with assurances as to confidentiality and prosocial benefit. Participants expressed mixed views about whether race and culture influence people's willingness to donate biospecimens. Specific recommendations to increase the likelihood of donation include providing patients with educational materials addressing the benefits of donation and the concerns about confidentiality and data usage, making donation convenient, and adopting a broad consent bio-banking policy.

Preclinical evaluation of 68Ga-radiolabeled trimeric affibody for PDGFRβ-targeting PET imaging of hepatocellular carcinoma

PurposeHepatocellular carcinoma (HCC) is a highly vascularized solid carcinoma and tumor vessel–targeted molecular imaging might be effective for early diagnosis of HCC. Herein, we developed a novel trimeric affibody (ZTRI) with highly specific binding to the platelet-derived growth factor receptor beta (PDGFRβ). The aim of this study is to evaluate the feasibility of 68Ga-radiolabeled ZTRI ([68Ga]Ga-DOTA-ZTRI) as PET tracer for diagnosis of HCC.MethodsThe bioinformatics analysis of clinical database and immunoblotting of clinical specimens were performed to validate the potential of PDGFRβ as HCC biomarker. The trimeric affibody ZTRI was conjugated with DOTA-NHS-ester and radiolabeled with 68Ga to produce [68Ga]Ga-DOTA-ZTRI conjugate. Immunoreactivity and specific uptake of [68Ga]Ga-DOTA-ZTRI were assessed by dose-dependent cell binding, autoradiography, and biodistribution analysis. [68Ga]Ga-DOTA-ZTRI PET/CT scanning of diethylnitrosamine (DEN)-induced primary HCC rats and a rare case of idiopathical HCC rhesus monkey was performed to evaluate the imaging capability and radiation dosimetry of [68Ga]Ga-DOTA-ZTRI in vivo.ResultsExcessive PDGFRβ was validated as a representative biomarker of HCC neovascularization. The radiolabeling of [68Ga]Ga-DOTA-ZTRI was achieved at more than 95% radiochemical yield. In vitro assays showed specific uptake of [68Ga]Ga-DOTA-ZTRI in HCC tumor vessels by autoradiography. Animal PET/CT imaging with [68Ga]Ga-DOTA-ZTRI successfully visualized the tumor lesions in primary HCC rats and rhesus monkey, and indicated radiation absorbed dose of 2.03E-02 mSv/MBq for each scanning.ConclusionsOur results demonstrated that [68Ga]Ga-DOTA-ZTRI conjugate could be applied as a promising PET tracer for early diagnosis of hepatocellular carcinoma.

The adoption of LI-RADS: a survey of non-academic radiologists.

To understand the practice and determinants of non-academic radiologists regarding LI-RADS and the four current LI-RADS algorithms: CT/MRI, contrast-enhanced ultrasound (CEUS), ultrasound (US), and CT/MRI Treatment Response. Seven themes were covered in this international survey, as follows: (1) demographics of participants and sub-specialty, (2) HCC practice and interpretation, (3) reporting practice, (4) screening and surveillance, (5) HCC imaging diagnosis, (6) treatment response, and (7) CT and MRI technique. Of the 232 participants, 69.4% were from the United States, 25.0% from Canada, and 5.6% from other countries and 45.9% were abdominal/body imagers. During their radiology training or fellowship, no formal HCC diagnostic system was used by 48.7% and LI-RADS was used by 44.4% of participants. In their current practice, 73.6% used LI-RADS, 24.7% no formal system, 6.5% UNOS-OPTN, and 1.3% AASLD. Barriers to LI-RADS adoption included lack of familiarity (25.1%), not used by referring clinicians (21.6%), perceived complexity (14.5%), and personal preference (5.3%). The US LI-RADS algorithm was used routinely by 9.9% of respondents and CEUS LI-RADS was used by 3.9% of the respondents. The LI-RADS treatment response algorithm was used by 43.5% of the respondents. 60.9% of respondents thought that webinars/workshops on LI-RADS Technical Recommendations would help them implement these recommendations in their practice. A majority of the non-academic radiologists surveyed use the LI-RADS CT/MR algorithm for HCC diagnosis, while nearly half use the LI-RADS TR algorithm for assessment of treatment response. Less than 10% of the participants routinely use the LI-RADS US and CEUS algorithms.

AFP deletion leads to anti-tumorigenic but pro-metastatic roles in liver cancers with concomitant CTNNB1 mutations

HCC remains one of the most prevalent and deadliest cancers. Serum AFP level is a biomarker for clinical diagnosis of HCC, instead the contribution of AFP to HCC development is clearly highly complex. Here, we discussed the effect of AFP deletion in the tumorigenesis and progression of HCC. AFP deletion in HepG2 cells inhibited the cell proliferation by inactivating PI3K/AKT signaling. Surprisingly, AFP KO HepG2 cells appeared the increasing metastatic capacity and EMT phenotype, which was attributed to the activation of WNT5A/β-catenin signal. Further studies revealed that the activating mutations of CTNNB1 was closely related with the unconventional pro-metastatic roles of AFP deletion. Consistently, the results of DEN/CCl4-induced HCC mouse model also suggested that AFP knockout suppressed the growth of HCC primary tumors, but promoted lung metastasis. Despite the discordant effect of AFP deletion in HCC progression, a drug candidate named OA showed the potent suppression of HCC tumor growth by interrupting AFP-PTEN interaction and, importantly, reduced the lung metastasis of HCC via angiogenesis suppression. Thus, this study demonstrates an unconventional effect of AFP in HCC progression, and suggests a potent candidate strategy for HCC therapy.

Noninvasive identification of molecular biomarkers of hepatocellular carcinoma in HCV-Egyptian patients

BackgroundThis study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender.MethodsThe expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases.ResultsThe baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1.ConclusionsOverall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.

AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study.

In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.

Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades.

Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.

MiRNome of Child A hepatocellular carcinoma in Egyptian patients.

Hepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes. Advances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC. In this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in "pathways in cancer and PI3K-Akt signaling pathway" KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC.

TWEAK Signaling-Induced ID1 Expression Drives Malignant Transformation of Hepatic Progenitor Cells During Hepatocarcinogenesis.

The malignant transformation of hepatic progenitor cells (HPCs) in the inflammatory microenvironment is the root cause of hepatocarcinogenesis. However, the potential molecular mechanisms are still elusive. The HPCs subgroup is identified by single-cell RNA (scRNA) sequencing and the phenotype of HPCs is investigated in the primary HCC model. Bulk RNA sequencing (RNA-seq) and proteomic analyses are also performed on HPC-derived organoids. It is found that tumors are formed from HPCs in peritumor tissue at the 16th week in a HCC model. Furthermore, it is confirmed that the macrophage-derived TWEAK/Fn14 promoted the expression of inhibitor of differentiation-1 (ID1) in HPCs via NF-κB signaling and a high level of ID1 induced aberrant differentiation of HPCs. Mechanistically, ID1 suppressed differentiation and promoted proliferation in HPCs through the inhibition of HNF4α and Rap1GAP transcriptions. Finally, scRNA sequencing of HCC patients and investigation of clinical specimens also verified that the expression of ID1 is correlated with aberrant differentiation of HPCs into cancer stem cells, patients with high levels of ID1 in HPCs showed a poorer prognosis. This study provides important intervention targets and a theoretical basis for the clinical diagnosis and treatment of HCC.

Pathological Basis of Imaging in Hepatocellular Carcinoma

AbstractHepatocellular carcinoma (HCC) is the most prevalent form of liver cancer with major risk factors being chronic liver disease (CLD) including chronic liver inflammation, steatohepatitis and certain viral infections (Hepatitis B and C). Due to the poor prognosis, early detection is key for effective management. Imaging of HCC has developed over the years with specificity as high as 95%. The Liver Imaging Reporting and Data System (LI-RADS) provides a standardized reporting format that can be followed by radiologists and clinicians alike. This article focuses on the pathological basis of imaging observations described in the LI-RADS lexicon. A clear understanding of the pathological basis of imaging will help the radiologist to be more confident to resolve unequivocal observations apart from achieving a high degree of specificity in the diagnosis of HCC.

Diagnostic and Prognostic Nomograms for Hepatocellular Carcinoma Based on PIVKA-II and Serum Biomarkers

Background: The aim of the present study was to develop an improved diagnostic and prognostic model for HBV-associated HCC by combining AFP with PIVKA-II and other potential serum/plasma protein biomarkers. Methods: A total of 578 patients, including 352 patients with HBV-related HCC, 102 patients with HBV-associated liver cirrhosis (LC), 124 patients with chronic HBV, and 127 healthy subjects (HS), were enrolled in the study. The serum levels of AFP, PIVKA-II, and other laboratory parameters were collected. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors, respectively. The diagnostic efficacy of the nomogram was evaluated using receiver operator curve (ROC) analysis and the prognostic performance was measured by Harrell’s concordance index (C-index). Results: AFP and PIVKA-II levels were significantly increased in HBV-related HCC, compared with those in HBV-associated LC and chronic HBV participants (p &lt; 0.05 and p &lt; 0.001, respectively). The diagnostic nomogram, which included age, gender, AFP, PIVKA-II, prothrombin time (PT), and total protein (TP), discriminated patients with HBV-HCC from those with HBV-LC or chronic HBV with an AUC of 0.970. In addition, based on the univariate and multivariate Cox regression analysis, PIVKA-II, γ-glutamyl transpeptidase, and albumin were found to be significantly associated with the prognosis of HBV-related HCC and were incorporated into a nomogram. The C-index of the nomogram for predicting 3-year survival in the training and validation groups was 0.75 and 0.78, respectively. The calibration curves for the probability of 3-year OS showed good agreement between the nomogram prediction and the actual observation in the training and the validation groups. Furthermore, the nomogram had a higher C-index (0.74) than that of the Child−Pugh grade (0.62), the albumin−bilirubin (ALBI) score (0.64), and Barcelona Clinic Liver Cancer (0.56) in all follow-up cases. Conclusion: Our study suggests that the nomograms based on AFP, PIVKA-II, and potential serum protein biomarkers showed a better performance in the diagnosis and prognosis of HCC, which may help to guide therapeutic strategies and assess the prognosis of HCC.

Comprehensive analysis reveals TSEN54 as a robust prognosis biomarker and promising immune-related therapeutic target for hepatocellular carcinoma.

Hepatocellular carcinoma represents the most common primary malignancy of all liver cancer types and its prognosis is usually unsatisfactory. TSEN54 encodes a protein constituting a subunit of the tRNA splicing endonuclease heterotetramer. Previous researches concentrated on the contribution of TSEN54 in pontocerebellar hypoplasia, but no studies have yet reported its role in HCC. TIMER, HCCDB, GEPIA, HPA, UALCAN, MEXPRESS, SMART, TargetScan, RNAinter, miRNet, starBase, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, GSEA, TISCH, TISIDB, GeneMANIA, PDB, GSCALite were applied in this research. We identified the upregulation of TSEN54 expression in HCC and related it to multiple clinicopathological features. Hypomethylation of TSEN54 was closely associated with its high expression. HCC sufferers who held high TSEN54 expression typically had shorter survival expectations. Enrichment analysis showed the involvement of TSEN54 in the cell cycle and metabolic processes. Afterward, we observed that TSEN54 expression level had a positive relationship to the infiltration level of multiple immune cells and the expression of several chemokines. We additionally identified that TSEN54 was related to the expression level of several immune checkpoints and TSEN54 was linked to several m6A-related regulators. TSEN54 is a prognostic marker of HCC. TSEN54 could become a prospective candidate for HCC diagnosis and therapy.

The impact of HIV infection on clinical presentation and mortality among persons with hepatocellular carcinoma in Kampala, Uganda

BackgroundHIV infection is associated with more rapid progression of some comorbidities. This study assessed the impact of HIV-infection on the presentation and outcome of HCC.MethodsHCC patients attending the Mulago National Referral Hospital in Uganda were enrolled into a natural history study of HCC between March 2015 and February 2019. Standardized methods were used to collect clinical, ultrasound and laboratory data at enrolment. HCC cases were confirmed and enrolled based on a combination of clinical, ultrasound, tumor marker and pathology data. Follow-up contact was made at one, three, six, and twelve months post-enrolment to determine vital status. Symptoms and signs at diagnosis and subsequent survival were compared by HIV status. Kaplan Meier curves were used to assess HCC survival.ResultsOf 441 persons with HCC, 383 (87.0%) died within 12 months following HCC diagnosis. The median (IQR) survival was 42 (20, 106) days. HIV infection was present in 79 (18%) cases. After adjusting for baseline demographic and clinical characteristics, HIV infection was associated with increased mortality but only among those with severe HIV-associated immunosuppression (CD4 count < 200 cells per cubic milliliter), aHR (95% C) = 2.12 (1.23–3.53), p = 0.004, and not among PLWH with ≥ 200 CD4 cells per cubic milliliter, aHR (95% C) = 1.15 (0.82–1.60), p = 0.417.ConclusionAmong relatively young Ugandans, HCC is a devastating disease with rapid mortality that is especially rapid among people living with HIV(PLWH). HIV was associated with slightly higher mortality, notably among PLWH with lower CD4 cell counts. As a substantial majority of PLWH diagnosed with HCC were engaged in HIV care, further investigation should determine the effectiveness of incorporating screening and early identification of HCC among high-risk individuals into existing HIV care programs. Concurrent with growing access to curative localized treatment for HCC in sub-Saharan Africa, leveraging HIV care infrastructure affords opportunities for earlier HCC intervention.

Abstract 5767: Pan-viral response in African Americans and European Americans with hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is often diagnosed at late-stages, with African Americans (AA) being diagnosed at a later stage with worse prognosis and high mortality rates. The poor screening and diagnosis of HCC and differences between racial/ethnic groups show a disproportion in mortality rates. Examining an individual’s viral exposure history might serve as a useful biomarker of early disease that could address and, potentially, alleviate this disparity. We aim to investigate whether viral features can be used to identify HCC and individuals at high risk (HR) of HCC. Additionally, we examine the racial/ethnic differences in viral exposures and whether viral exposure history accounts for epidemiological disparity described previously. Herein we use a technique called VirScan, which conjugates Phage Immunoprecipitation sequencing (PhIP-seq) and DNA sequencing, to profile an individual’s epitope antibody repertoire upon viral exposure. We performed VirScan on serum and plasma samples from 199 AA (130 HR and 79 HCC) and 260 European Americans (EA) (210 HR and 50 HCC) participants from the NCI-UMD cohort (NCT00913757; clinicaltrials.gov). We used a machine-learning XGBoost model to classify viral features that can discriminate HCC or HR. A composite viral score was generated using the SHAP value of the most significant viral features from the model with a higher score more predictive of HCC. Secondary analyses using Wilcoxon-Rank sums tests and Cox proportional hazard analysis revealed that while race/ethnicity did not differentially predict HCC in this cohort, the viral score was significantly higher in AA compared to EA in the HR group (p = 0.027). XGBoost search identified 235 important viral features which distinguish HCC from HR. Out of the 235 viral features, 20 viruses were different between AA and EA (FDR &amp;lt; 0.05). We also found the viral score was positively associated with incident mortality in HCC group over the study period of 8 years (p=0.03). Thus, we demonstrate that the viral history of an individual might be useful in early detection of HCC. This approach could be used to account for the disparities we see in both incidence and mortality of HCC between AA and EA. Citation Format: Theressa Ewa, Whitney L. Do, Limin Wang, Marshonna Forgues, Xin W. Wang. Pan-viral response in African Americans and European Americans with hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5767.

Early diagnosis and prognosis of hepatocellular carcinoma based on a ceRNA array

Abstract Objectives Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths, due to high morbidity, a low early diagnosis rate, and poor prognosis. It is essential to explore competitive endogenous RNA (ceRNA) arrays for early diagnosis and prognosis of HCC. Methods The original gene expression profiles of differentially expressed lncRNA, miRNA and mRNA in HCC were downloaded from TCGA database. Differentially expressed lncRNA-miRNA and miRNA-mRNA interaction pairs were extracted from miRcode and starBase, a ceRNA network was constructed, and GO annotation and KEGG pathway analyses were performed. Cox regression and Kaplan-Meier survival analysis screening identified core genes in the network associated with HCC survival, centering on miRNA, which were screened using ceRNA arrays. qRT-PCR was used to detect the expression level of key genes in clinical samples. Dual luciferase reporter gene assays were used to verify the target binding relationship among lncRNA, mRNA, and miRNA. ROC curves were used to analyze the diagnostic efficacy of the ceRNA array. Results A total of 8 lncRNAs, 5 miRNAs, and 21 mRNAs were used to construct a ceRNA network. Functional enrichment analysis showed that mRNAs in the ceRNA network were mainly enriched in 14 signaling pathways, especially microRNAs in cancer. Survival analysis showed that lncRNA FOXD2-AS1 and miRNA miR-9-5p were related to the prognosis of HCC, and the targeted binding relationships between mRNAs. STMN1, COL15A1, and CCNE2 and miR-9-5p from the TargetScan, starBase, miRDB, and PicTar databases were reliable. qRT-PCR showed that expression levels of FOXD2-AS1, miR-9-5p, STMN1, COL15A1, and CCNE2 were upregulated in HCC tissues. Dual luciferase reporter assays showed that FOXD2-AS1 and STMN1 had a targeted binding relationship with miR-9-5p, but not with COL15A1 or CCNE2. The area under the curve of the candidate ceRNA array (FOXD2-AS1/miR-9-5p/STMN1/COL15A1/CCNE2) was higher than that of each member and ceRNA combination (FOXD2-AS1/miR-9-5p/STMN1). Conclusions The candidate ceRNA array formed by FOXD2-AS1/miR-9-5p/STMN1/COL15A1/CCNE2 could be a biomarker for early diagnosis and prognosis of HCC.

Evaluation of AFP for diagnosis of HCC in Egyptian patients

Evaluation of AFP for diagnosis of HCC in Egyptian patients

A new classification and regression tree algorithm: Improved diagnostic sensitivity for HCC ≤ 3.0 cm using gadoxetate disodium-enhanced MRI

PurposeTo develop and validate an effective algorithm, based on classification and regression tree (CART) analysis and LI-RADS features, for diagnosing HCC ≤ 3.0 cm with gadoxetate disodium‑enhanced MRI (Gd-EOB-MRI). MethodWe retrospectively included 299 and 90 high-risk patients with hepatic lesions ≤ 3.0 cm that underwent Gd-EOB-MRI from January 2018 to February 2021 in institution 1 (development cohort) and institution 2 (validation cohort), respectively. Through binary and multivariate regression analyses of LI-RADS features in the development cohort, we developed an algorithm using CART analysis, which comprised the targeted appearance and independently significant imaging features. On per-lesion basis, we compared the diagnostic performances of our algorithm, two previously reported CART algorithms, and LI-RADS LR-5 in development and validation cohorts. ResultsOur CART algorithm, presenting as a decision tree, included targetoid appearance, HBP hypointensity, nonrim arterial phase hyperenhancement (APHE), and transitional phase hypointensity plus mild-moderate T2 hyperintensity. For definite HCC diagnosis, the overall sensitivity of our algorithm (development cohort 93.2%, validation cohort 92.5%; P < 0.006) was significantly higher than those of Jiang’s algorithm modified LR-5 (defined as targetoid appearance, nonperipheral washout, restricted diffusion, and nonrim APHE) and LI-RADS LR-5, with the comparable specificity (development cohort: 84.3%, validation cohort: 86.7%; P ≥ 0.006). Our algorithm, providing the highest balanced accuracy (development cohort: 91.2%, validation cohort: 91.6%), outperformed other criteria for identifying HCCs from non-HCC lesions. ConclusionsIn high-risk patients, our CART algorithm developed with LI-RADS features showed promise for the early diagnosis of HCC ≤ 3.0 cm with Gd-EOB-MRI.

Assessment of clinico-epidemiological profile of Hepatocellular carcinoma in the last two decades

BackgroundHepatocellular carcinoma represents 85%—90% of primary liver tumors; it represents the 2nd leading cause of cancer-related death all over the world. There is a growing incidence of HCC worldwide and similarly, the incidence of HCC has almost doubled over the last decade in Egypt.Aim of the workTo assess clinico-epidemiological character of HCC in the last two decades and to compare between the first and second decade regarding these characters.Patients and methodsThis retrospective study included 497 HCC patients’ data collected from Clinical Oncology and Nuclear Medicine Department from 1999 to 2019, HCC patients were classified into 1st decade (from 1999 to 2009) and 2nd decade (2010 – 2019). Diagnosis of HCC was based on clinical, laboratory, (AFP), and radiological examinations (The abdominal US and triphasic CT scan).ResultsThe study revealed that the average age of HCC cases was 57 years, the majority of these were males (88%), residents in rural areas (70%), about one-fourth of them, were smokers (26.4%), DM was present in 14% of these while only 7% were hypertension. Thirty presents (30%) of them were represented by ascites and (20%) by hepatic encephalopathy of different grades. The majority of HCC patients (92.2%) have HCV Abs positive. HBS Ag was positive in 2.4% while mixed infection (HCV Abs + ve and HBS Ag + ve) was in 2% of patients only. The median level of AFP was 300 ng/ml.The severity of underlying chronic liver disease was assessed by the Child–Pugh score the mean score was 7.5 (from 6–11) and the MELD score (the mean score was 18.8 (from 6–29).Regarding tumor characteristics, HCC mass was located in the Right lobe of the liver in (63.8%), in the left lobe in (26.6%) and both lobes were affected in 9.6%. A single focal hepatic lesion was detected in about 60% of patients, 3 focal lesions in about 20%, and two focal lesions or multifocal HCC in the remaining percent. The median size of the largest tumor’s diameter was 5 cm by the US and 5.3 cm by the triphasic CT. PVT, vascular invasion, LN, and distant metastasis were detected in (35.6%), (40%), (40%) and (54%) of patients respectively. In less than one-third of HCC cases, the tumors were within Milan criteria (30%).ConclusionThe 1st decade showed a significantly higher frequency of patients presented with marked splenomegaly and splenectomy, while the second decade showed a significantly higher frequency in patients who reside in rural areas. Higher frequency of DM, advanced hepatic encephalopathy grade III/ IV, and unfortunately more aggressive tumors with PVT, vascular invasion, LN metastasis, and distant metastasis were detected in the 2nd decade.

The role of enhancing capsule and modified capsule appearances in LI-RADS for diagnosing HCC ≤ 3.0cm on gadoxetate disodium-enhanced MRI.

To evaluate the value of using enhancing capsule (EC) or modified capsule appearance as a major feature in LI-RADS for diagnosing HCC ≤ 3.0cm on gadoxetate disodium-enhanced MRI (Gd-EOB-MRI), and to explore the relationship between the imaging features and the histological fibrous capsule. This retrospective study enrolled 342 hepatic lesions ≤ 3.0cm in 319 patients that underwent Gd-EOB-MRIs from January 2018 to March 2021. During dynamic phases and hepatobiliary phase, the modified capsule appearance added the nonenhancing capsule (NEC) (modified LI-RADS + NEC) or corona enhancement (CoE) (modified LI-RADS + CoE) to EC as an alternative capsule appearance. Inter-reader agreement of imaging features was assessed. The diagnostic performances of LI-RADS, LI-RADS with EC ignored, and two modified LI-RADS were compared, followed by Bonferroni correction. Multivariable regression analysis was performed to identify the independent features associated with the histological fibrous capsule. The inter-reader agreement on EC (0.64) was lower than that on the NEC alternative (0.71) but better than that on CoE alternative (0.58). For HCC diagnosis, compared to LI-RADS, LI-RADS with EC ignored showed significantly lower sensitivity (72.7% vs. 67.4%, p < 0.001) with comparable specificity (89.3% vs. 90.7%, p = 1.000). Two modified LI-RADS showed slightly higher sensitivity and lower specificity than LI-RADS, without statistical significance (all p ≥ 0.006). The AUC was highest with modified LI-RADS + NEC (0.82). Both EC and NEC were significantly associated with the fibrous capsule (p < 0.05). EC appearance improved the diagnostic sensitivity of LI-RADS for HCC ≤ 3.0cm on Gd-EOB-MRI. Considering NEC as an alternative capsule appearance allowed for better inter-reader reliability and comparable diagnostic ability. • Using the enhancing capsule as a major feature in LI-RADS significantly improved the sensitivity of diagnosing HCC ≤ 3.0cm without reducing specificity on gadoxetate disodium-enhanced MRI. • Compared to the corona enhancement, the nonenhancing capsule might be a preferable alternative capsule appearance for diagnosing HCC ≤ 3.0cm. • Capsule appearance should be considered a major feature in LI-RADS for diagnosing HCC ≤ 3.0cm, regardless whether the capsule appears to be enhancing or nonenhancing.