Hepatocellular carcinoma (HCC) counts around 90% of primary liver cancers. The poor prognosis of patients with HCC is due to a late diagnosis. Therefore, it is important to detect new biomarkers which can be used as complements or substitutes for AFP in HCC diagnosis and to be a proper tool for assessment of tumor spread and patient prognosis as these markers can be a tool for HCC treatment and outcomes [17, 18].
Autophagy is a degradation of lysosomes which is important for cell survival under starvation, stress, and infection. The mechanism is regenerating of energy from intracellular materials (cytoplasm, organelles, protein aggregates, etc.) to meet energy requirements in low-nutritional conditions [19].
In this study, serum ATG 5 was significantly lower in patients with HCC than in patients with cirrhosis, but there was no statistically significant difference between patients with cirrhosis than control individuals. The ROC curve for ATG5 for detection of HCC from cirrhosis was significant, its diagnostic performance was 0.670* (p < 0.024*), and the cutoff point discriminating HCC from liver cirrhosis was < 95.7 with sensitivity of 76.6%, specificity of 53.33%, positive predictive value of 62.2%, negative predictive value of 69.9%, and accuracy of 65%.
This is in concordance with Yang et al. [20] who found that Atg5 were decreased in human HCC tissue in comparison with control tissue which suggests that autophagy is decreased in HCC. Also, this result is consistent with findings in Takamura et al.’s [21] study that autophagy might be a suppressor mechanism in HCC. Therefore, autophagic deficiency increases tumor growth in HCC.
In this study, serum Beclin 1 was significantly higher in HCC patients than patients with cirrhosis but there was no statistically significant difference between patients with cirrhosis than control individuals (p value < 0.001).
The ROC curve for Beclin 1 for detection of HCC from liver cirrhosis was significant, its diagnostic performance was 0.824 (p < 0.001), and the cutoff point discriminating HCC from cirrhosis was > 5.3 with sensitivity of 93.33, specificity of 66.67%, positive predictive value of 73.3%, negative predictive value of 90.9%, and accuracy of 80%.
In contrast to the results of Qiu et al. [22] that have detected that Beclin1 expression in HCC is significantly lower than that in normal and cirrhotic tissues. They have also shown that Beclin1 expression is correlated with liver cirrhosis and vascular invasion but not with TNM stage, AFP level, number of tumors, and capsule.
In this study, we developed a simple score that consisted of routinely available clinical and laboratory parameters to predict the risk of HCC in patients with HCV-related cirrhosis. This prediction score is accurate. The score ranged from 0 to 4, it is composed of Cachexia which was assigned 1 point since its estimated coefficient in logistic regression model was 1.348, ATG 5 < 95.7 was assigned 1 point as its estimated coefficient I logistic regression model was 1.288, and Beclin 1 > 5.3 was given 2 points for its estimated coefficient in logistic regression model was 1.7.
A cutoff point 2 is used to predict HCC in HCV-related cirrhotic patients. At cutoff value of 2 scoring points, the PPV was 83.3% and NPV was 75.8%. Using a cutoff of 2 points led to false negative results in 4 out of 30 with HCC (sensitivity 70%, specificity 94%).
Compared with current guidelines, the prediction score provides more systematic stratification of HCC risk [23, 24].
The score suggests that patients with cachexia can predict the development of HCC. And this is consistent with Nozoe et al. [25], who used the prognostic nutritional index (PNI) as a prognostic marker in a number of gastrointestinal malignancies, and more recently, in a study by Proctor et al. [26], the PNI was found to affect the prognosis in malignancy regardless of the site of origin.
Also, in this study, assessment of serum marker may have the advantage of being noninvasive rather than other studies in which assessment of Beclin 1 and ATG 5 used the invasive technique by liver biopsy.