Original article
Talin-1; other than a potential marker for hepatocellular carcinoma diagnosis

https://doi.org/10.1016/j.ajg.2020.04.017Get rights and content

Abstract

Background and study aims

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Talin-1 was previously proposed as a potential novel biomarker for HCC diagnosis but with limited and inconsistent data. We aimed to study the possible role of talin-1 in diagnosis and prognostic stratification of patients with hepatocellular carcinoma.

Patients and methods

Ninety-six patients were recruited and classified into three groups; 1) cirrhosis group: 40 patients with liver cirrhosis, 2) HCC group: 40 patients with HCC, 3) control group: 16 healthy volunteers with matched age and sex. Serum talin-1 level was detected using enzyme-linked immunosorbent assay (ELISA).

Results

The highest levels of talin-1 were observed among the HCC group followed by cirrhosis then control groups (p = 0.000). In the HCC group, a significant correlation was found between talin-1 and each of multifocal HCC (p = 0.013), portal vein invasion (p = 0.022) and presence of ascites (p = 0.001), while no significant correlation was detected with tumour foci size (p = 0.605). For HCC detection, talin-1 had AUC = 0.858, 100% sensitivity and 65% specificity, while AFP had AUC = 1.000, 100% sensitivity and specificity.

Conclusion

Talin-1 is a potential marker for diagnosis and prognostic assessment of HCC. Further studies are needed to investigate the ultimate diagnostic and prognostic utility of serum talin-1.

Introduction

The most serious liver malignancy is hepatocellular carcinoma (HCC) [1]. It is the sixth malignancy in the world and the third of deaths related to cancer [2], [3]. HCC development is associated with various factors such as HCV, HBV, alcohol, metabolic and cholestatic liver diseases [4]. Patients are often diagnosed at an advanced stage and show a poor prognosis [5] with limited treatment options [6]. Consequently, novel diagnostic methods are required for the early detection and effective treatment of HCC [7].

Alpha-foetoprotein (AFP) has been used as a diagnostic tumour marker for HCC. Previous studies reported that only about 33% to 65% of HCC patients had high serum AFP levels. Moreover, 15% to 58% of cirrhotic patients had non-specific increased levels of AFP [8]. Accordingly, there is a substantial necessity for new biomarkers for HCC diagnosis [9].

Talin-1 is a cytoplasmic macromolecular protein that is encoded by TLN1 gene in humans. It has been reported that talin-1 interact with multiple adhesion molecules (e.g. integrin and F-actin) to initiate the integrin/focal adhesion kinase (FAK) pathway [10], [11]. Consequently, integrins enhance cell-to-extracellular matrix interactions, thus transduce bidirectional signals and eventually regulate adhesion, apoptosis and tumour growth [12]. Altering the adhesion of tumour cells is the initial step of tumour cells invasion and metastasis [13]. Thus, talin-1 is accused in the cancer progression and metastasis through integrin-mediated signalling transduction pathway [14].

Talin-1 was studied in several malignancies such as colon [15], prostate [16] and oral squamous cell carcinoma [17]. In addition, it was investigated as a biomarker for the process of the carcinogenesis, invasion, metastasis and clinical diagnosis of HCC [12], [13], [18]. Such results have suggested that talin-1 is a potential diagnostic marker for HCC. However, it is still unknown whether talin-1 promoted HCC growth and metastasis, and the role of talin-1 in HCC progression remained unclear. In this study, we aimed to investigate the possible role of talin-1 in the diagnosis and prognostic stratification of patients with hepatocellular carcinoma.

Section snippets

Patients and methods

From August 2017 to March 2018, 96 subjects were consecutively enrolled in this observational cohort study. They were classified into cirrhosis group (40 patients), HCC group (40 patients) and control group (16 healthy subjects). Cirrhosis was diagnosed based on clinical, laboratory, histological or radiological findings [19]. HCC was diagnosed according to the EASL guidelines [20]. Patients with autoimmune liver diseases, alcohol abuse, sepsis or other malignancies were excluded.

All

Statistical analysis

Data were analysed using IBM® SPSS® Statistics® version 21 for Windows. Chi-square test was done for qualitative variable analysis. Quantitative data were expressed as mean ± standard deviation if parametric (normally distributed) or median and interquartile range if non-parametric (non-normally distributed). Comparisons between two groups were performed by using the Student’s t-test for parametric data and Mann-Whitney test for non-parametric data. Comparisons between multiple groups were

Results

The control group included 4 females and 12 males with a mean age of 44 ± 7 years, while the cases groups included 24 females and 56 males with a mean age of 45 ± 9 years. No significant difference was observed between the studied groups as regards age and sex (p = 0.07 and p = 0.92, respectively).

The HCC group included 8 patients with multifocal tumour foci, 11 patients with tumour foci size ≥ 5 cm, 15 patients with portal vein invasion, and 23 patients with ascites.

There was a statistically

Discussion

The incidence of HCC is rising worldwide due to the increasing prevalence of HBV and HCV infections [21], [22]. In developed countries, approximately 0.5 million cases of HCV infection are reported annually, with infection in association with HCC in 50–70% of cases [23]. Recently, non-alcoholic steatohepatitis has emerged as a relevant risk factor for HCC.

In most countries, the mortality rate of HCC almost equals the incidence rate, indicating the lack of effective therapies at the time of

Declaration of competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (31)

  • P.P. Song et al.

    Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma

    World J Gastroenterol

    (2016)
  • W.W. Zhu et al.

    Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma

    Clin Cancer Res

    (2013)
  • I. Teofănescu et al.

    Surveillance of cirrhosis for hepatocellular carcinoma–clinical validation of new serological biomarkers for improved diagnosis

    Rev Med Chir Soc Med Nat Iasi

    (2010)
  • K. Austen et al.

    Extracellular rigidity sensing by talin isoform-specific mechanical linkages

    Nat Cell Biol

    (2015)
  • K.P. Fang et al.

    Talin-1 correlates with reduced invasion and migration in human hepatocellular carcinoma cells

    Asian Pac J Cancer Prev

    (2014)
  • Cited by (5)

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