# Circulating Biomarkers for the Detection of Human Liver Diseases

> **NIH VA I01** · OKLAHOMA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

Hepatocellular Carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. The risk
of liver fibrosis and HCC increases significantly in hepatitis C virus (HCV) carriers with obesity and diabetes,
which is a rising trend in the USA. Thus, HCC represents a wide-ranging public health issue. Our recent
studies have revealed a positive correlation between overexpression of doublecortin-like kinase (DCLK1) and
cancers of the liver, colon, intestine and pancreas. Recently, we have demonstrated that increased expression
of DCLK1 in patients with cirrhosis and HCC. Furthermore, we demonstrated that DCLK1 expression tends to
increase during progression of liver diseases such as cirrhosis and HCC. Downregulation of DCLK1 resulted in
marked reduction of HCC cell proliferation and tumor-like growth in immunodeficient mice. Our studies indicate
that DCLK1-affected biological processes in the pancreas and colon cancers including epithelial-to-
mesenchymal transition (EMT) and cMYC pathways. For example, knockdown of DCLK1 results in marked
upregulation of tumor-suppressor miRNAs (let-7a, miR-200, miR-144, and miR-145/143) with a concomitant
decrease in cMYC, ZEB1/ZEB2, KRAS, NOTCH1, VEGFR1 and 2, and pluripotency factors OCT4, SOX2,
NANOG and KLF4. Thus, DCLK1 appears to be a well-justified targets for anti-tumor treatment and is a
potential prognostic biomarker for detecting/identifying/differentiating various stages of cirrhosis (based on
Child-Pugh Score A – C) and HCC. Furthermore, several miRNAs (miR-21, miR-199a, and miR-301) are
upregulated in cirrhosis and HCC, correlated with diseases outcomes. Furthermore these miRNAs are known
to regulate/induce EMT and oncogenesis. Based on these observations, we hypothesize that DCLK1 and
miRNAs are upregulated and can be detected in plasma of patients with HCC, and can be a biomarker
for the detection of cirrhosis and HCC. The expression of DCLK1 and miRNAs will be compared to
AFP-L3 levels in patients with fibrosis, cirrhosis and HCC. Here we will collect blood from 4 groups of
patients – healthy controls, patients with fibrosis (but non-cirrhotic and non-HCC; classified based on
FIB4 scoring), cirrhosis (non-HCC; Child-Pugh A – C) and HCC (either Child A, B or C). Samples will
be collected at OKC VAMC (test cohort) and also at VA St. Louis Health Care System (validation
cohort). We will test the hypothesis with the following specific aims. Aim 1. Identify candidate miRNAs-
regulating EMT in the blood stream of patients with liver fibrosis or HCC. We will isolate total miRNAs
from the plasma (collected from clinically defined fibrosis, cirrhosis and HCC) and perform microarray analysis
to identify various miRNAs upregulated that have been associated with the regulation of EMT, in patients with
liver diseases. We will also determine expression of specific miRNAs regulated by DCLK1. Aim 2. Determine
whether plasma levels of DCLK1 are associated with the development of HCC. We will employ enz...

## Key facts

- **NIH application ID:** 10049186
- **Project number:** 5I01CX001686-03
- **Recipient organization:** OKLAHOMA CITY VA MEDICAL CENTER
- **Principal Investigator:** Courtney Wayne Houchen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049186

## Citation

> US National Institutes of Health, RePORTER application 10049186, Circulating Biomarkers for the Detection of Human Liver Diseases (5I01CX001686-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10049186. Licensed CC0.

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