Circulating miRNA's biomarkers for early detection of hepatocellular carcinoma in Egyptian patients based on machine learning algorithms

Abstract

Liver cancer, which ranks sixth globally and third in cancer-related deaths, is caused by chronic liver disorders and a variety of risk factors. Despite therapeutic improvements, the prognosis for Hepatocellular Carcinoma (HCC) remains poor, with a 5-year survival rate for advanced cases of less than 12%. Although there is a noticeable decrease in the frequency of cases, liver cancer remains a significant worldwide health concern, with estimates surpassing one million cases by 2025. The prevalence of HCC has increased in Egypt, and it includes several neoplasms with distinctive messenger RNA (mRNA) and microRNA (miRNA) expression profiles. In HCC patients, certain miRNAs, such as miRNA-483-5P and miRNA-21, are upregulated, whereas miRNA-155 is elevated in HCV-infected people, encouraging hepatocyte proliferation. Short noncoding RNAs called miRNAs in circulation have the potential as HCC diagnostic and prognostic markers. This paper proposed a model for examining circulating miRNAs as diagnostic and predictive markers for HCC in Egyptian patients and their clinical and pathological characteristics. The proposed HCC detection model consists of three main phases: data preprocessing phase, feature selection based on the proposed Binary African Vulture Optimization Algorithm (BAVO) phase, and finally, classification as well as cross-validation phase. The first phase namely the data preprocessing phase tackle the main problems associated with the adopted datasets. In the feature selection based on the proposed BAVO algorithm phase, a new binary version of the BAVO swarm-based algorithm is introduced to select the relevant markers for HCC. Finally, in the last phase, namely the classification and cross-validation phase, the support vector machine and k-folds cross-validation method are utilized. The proposed model is evaluated on three studies on Egyptians who had HCC. A comparison between the proposed model and traditional statistical studies is reported to demonstrate the superiority of using the machine learning model for evaluating circulating miRNAs as diagnostic markers of HCC. The specificity and sensitivity for differentiation of HCC cases in comparison with the statistical-based method for the first study were 98% against 88% and 99% versus 92%, respectively. The second study revealed the sensitivity and specificity were 97.78% against 90% and 98.89% versus 92.5%, respectively. The third study reported 83.2% against 88.8% and 95.80% versus 92.4%, respectively. Additionally, the results show that circulating miRNA-483-5p, 21, and 155 may be potential new prognostic and early diagnostic biomarkers for HCC.

Keywords: Hepatocellular carcinoma; Liver cancer; Machine learning; Swarm optimization; miRNA.

Figure 1

Different parameters and attributes for HCC studies.

Figure 2

The block-diagram of the proposed HCC detection model.

Figure 3

Number of outliers for the adopted datasets for each study.

Figure 4

The classes’ distribution before and after using the SASYNO method; (a) the first study with miRNA 483-5p, (b) The second study with miRNA-21, and (c) the third study with miRNA-155.

Figure 5

Correlation between features result; (a) the correlation of APF, miRNA, and the class for the first study miRNA 483-5p, (b) the correlation of APF, miRNA, and the class for the second study with miRNA-21, (c) the correlation of APF, miRNA, and the class for the third study with miRNA-155.