Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities

Golabi, Pegah; Fazel, Sofie; Otgonsuren, Munkhzul; Sayıner, Mehmet; Locklear, Cameron T.; Younossi, Zobair M.

doi:10.1097/md.0000000000005904

Cited by 208 publications

(162 citation statements)

References 45 publications

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“…While there has been considerable improvement in the diagnosis and treatment of HCC over the last decade, the incidence of HCC remains high, therapy response low, predisposition to developing resistance to contemporary chemo-and/or radio-therapy high, and treatment failure more common, as is evidenced by increasing incidence and mortality rates over the last 10 years, coupled with a relatively low~50% 2-year survival rate and perplexing 10% 5-year survival rate in the United States [21]; Thus, managing HCC remains a medical enigma, requiring the discovery or identification of novel actionable molecular targets and development of a more effective therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Chang

Bamodu

Ong

et al. 2020

Cells

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Background: With recorded under-performance of current standard therapeutic strategies as highlighted by high rates of post-treatment (resection or local ablation) recurrence, resistance to chemotherapy, poor overall survival, and an increasing global incidence, hepatocellular carcinoma (HCC) constitutes a medical challenge. Accumulating evidence implicates the presence of HCC stem cells (HCC-SCs) in HCC development, drug-resistance, recurrence, and progression. Therefore, treatment strategies targeting both HCC-SCs and non-CSCs are essential. Methods: Recently, there has been an increasing suggestion of MALAT1 oncogenic activity in HCC; however, its role in HCC stemness remains unexplored. Herein, we investigated the probable role of MALAT1 in the SCs-like phenotype of HCC and explored likely molecular mechanisms by which MALAT1 modulates HCC-SCs-like and metastatic phenotypes. Results: We showed that relative to normal, cirrhotic, or dysplastic liver conditions, MALAT1 was aberrantly expressed in HCC, similar to its overexpression in Huh7, Mahlavu, and SK-Hep1 HCC cells lines, compared to the normal liver cell line THLE-2. We also demonstrated a positive correlation between MALAT1 expression and poor cell differentiation status in HCC using RNAscope. Interestingly, we demonstrated that shRNA-mediated silencing of MALAT1 concomitantly downregulated the expression levels of β-catenin, Stat3, c-Myc, CK19, vimentin, and Twist1 proteins, inhibited HCC oncogenicity, and significantly suppressed the HCC-SCs-related dye-effluxing potential of HCC cells and reduced their ALDH-1 activity, partially due to inhibited MALAT1-β-catenin interaction. Additionally, using TOP/FOP (TCL/LEF-Firefly luciferase) Flash, RT-PCR, and western blot assays, we showed that silencing MALAT1 downregulates β-catenin expression, dysregulates the canonical Wnt signaling pathway, and consequently attenuates HCC tumorsphere formation efficiency, with concurrent reduction in CD133+ and CD90+ HCC cell population, and inhibits tumor growth in SK-Hep1-bearing mice. Conclusions: Taken together, our data indicate that MALAT1/Wnt is a targetable molecular candidate, and the therapeutic targeting of MALAT1/Wnt may constitute a novel promising anticancer strategy for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Chang

Bamodu

Ong

et al. 2020

Cells

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“…Despite demonstrating a significant improvement of survival over time, the median survival of 18.6 months in the later era still seems rather low. Golabi and colleagues47 looked at 2‐year survival rates of patients with HCC in the Surveillance, Epidemiology and End Results database between 2001 and 2009 and found that 75.4% of the patients had died within 2 years; further subanalysis showed mortality within 2 years for those who underwent liver transplant, hepatic resection, and nonsurgical treatment to be 29.1%, 43.7%, and 85.3%, respectively. It is likely that the high mortality rate of those patients in the nonsurgical treatment group greatly impacted the overall survival rates in their study.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Goh

Chang

et al. 2017

Hepatology Communications

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Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers globally. With advances in therapy for chronic viral hepatitis, changing social circumstances, and increasing practice of HCC surveillance, the epidemiology of HCC is expected to change over time. We explored the temporal trends in HCC in Singapore, a multiethnic Asian country, over the last 3 decades. Patients with HCC were prospectively enrolled and stratified into two cohorts (C1, 1988‐2002; C2, 2003‐2016). Patient and tumor characteristics, management, and survival were compared between the two cohorts, and a survival census was performed on October 31, 2015. There were 1,401 patients, and the mean age at diagnosis of HCC for C1 and C2 was 60.1 and 63.5 years, respectively. Male patient preponderance decreased significantly, with the male to female ratio falling from 5.2:1 to 3.9:1 between C1 and C2. Hepatitis B, although still the predominant risk factor for HCC, showed a significant decline from C1 to C2 (76.5% to 68.2%), while the nonviral etiology increased significantly over the same period (14.4% versus 25.0%, respectively). Significantly more patients in C2 than C1 were diagnosed through surveillance (39.2% versus 11.3%, respectively) and had better physical performance (Eastern Cooperative Oncology Group 0, 62.1% versus 20.4%, respectively). While Child‐Pugh status was comparable, significantly more patients in C2 than C1 had early stage disease (Barcelona Clinic Liver Cancer 0‐A, 39.5% versus 7.4%, respectively), which translated into significantly higher median survival (18.6 months versus 3.8 months, respectively). Conclusion: Over the past 3 decades, hepatitis B‐related HCC has been decreasing while HCC due to nonviral etiology has been increasing significantly. Surveillance to diagnose early stage HCC is important in improving the outcome of HCC. (Hepatology Communications 2017;1:564–571)

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“…(2) In the United States, 2-year survival with HCC ranges from 30% to 44%. (1,3) Early diagnosis and treatment is essential to curbing the high mortality associated with HCC and other liver tumors. Ultrasound imaging and measuring alpha-fetoprotein (AFP) are two commonly used approaches to screen for HCC; however, there are important limitations to both of these methodologies.…”

mentioning

confidence: 99%

Breath Metabolomics Provides an Accurate and Noninvasive Approach for Screening Cirrhosis, Primary, and Secondary Liver Tumors

Miller‐Atkins¹,

Acevedo‐Moreno²,

Grove³

et al. 2020

Hepatol Commun

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Hepatocellular carcinoma (HCC) and secondary liver tumors, such as colorectal cancer liver metastases are significant contributors to the overall burden of cancer-related morality. Current biomarkers, such as alpha-fetoprotein (AFP) for HCC, result in too many false negatives, necessitating noninvasive approaches with improved sensitivity. Volatile organic compounds (VOCs) detected in the breath of patients can provide valuable insight into disease processes and can differentiate patients by disease status. Here, we investigate whether 22 VOCs from the breath of 296 patients can distinguish those with no liver disease (n = 54), cirrhosis (n = 30), HCC (n = 112), pulmonary hypertension (n = 49), or colorectal cancer liver metastases (n = 51). This work extends previous studies by evaluating the ability for VOC signatures to differentiate multiple diseases in a large cohort of patients. Pairwise disease comparisons demonstrated that most of the VOCs tested are present in significantly different relative abundances (false discovery rate P < 0.1), indicating broad impacts on the breath metabolome across diseases. A predictive model developed using random forest machine learning and cross validation classified patients with 85% classification accuracy and 75% balanced accuracy. Importantly, the model detected HCC with 73% sensitivity compared with 53% for AFP in the same cohort. An added value of this approach is that influential VOCs in the predictive model may provide insight into disease etiology. Acetaldehyde and acetone, both of which have roles in tumor promotion, were considered important VOCs for differentiating disease groups in the predictive model and were increased in patients with cirrhosis and HCC compared to patients with no liver disease (false discovery rate P < 0.1). Conclusion: The use of machine learning and breath VOCs shows promise as an approach to develop improved, noninvasive screening tools for chronic liver disease and primary and secondary liver tumors. (Hepatology Communications 2020;4:1041-1055).

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Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities

Abstract: Supplemental Digital Content is available in the text

Cited by 208 publications

References 45 publications

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Targeting the Epigenetic Non-Coding RNA MALAT1/Wnt Signaling Axis as a Therapeutic Approach to Suppress Stemness and Metastasis in Hepatocellular Carcinoma

Deciphering the epidemiology of hepatocellular carcinoma through the passage of time: A study of 1,401 patients across 3 decades

Breath Metabolomics Provides an Accurate and Noninvasive Approach for Screening Cirrhosis, Primary, and Secondary Liver Tumors

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