Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2137
Peer-review started: May 4, 2021
First decision: June 16, 2021
Revised: June 21, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: December 27, 2021
Autophagy is one of the pathways affected in hepatocellular carcinoma (HCC). Genetic regulation of this pathway through the SQSTM1 gene was established. Autophagy is responsible for the destruction of cellular components through lysosomal degradation. This process is responsible for cellular recycling and preservation. It protects from cancerous transformation, thus any imbalance in this mechanism will increase the risk of cancer.
We aimed to establish the genetic-epigenetic-phenotypic pathway related to the autophagic process in the pathogenesis of HCC and whether these studied biomarkers could be used as surrogate diagnostic markers for autophagy pathway in HCC.
We examined hsa-miR-519d microRNA effect on HCC and its association with the SQSTM1 genetic marker. We also examined the sensitivity and specificity of those biomarkers in the diagnosis of early-stage HCC cases.
This is an observational study. We evaluated the candidate biomarkers through bioinformatics, and after establishing a computational statistical relation, we proceeded with their clinical association through laboratory validation. We measured the genetic and epigenetic biomarkers in the serum samples taken from HCC patients, chronic liver disease patients, and healthy participants. We used reverse transcription-polymerase chain reaction and quantitative reverse transcription-polymerase chain reaction.
We determined the sensitivity and specificity of each biomarker separately and combined as compared to the established alpha-fetoprotein (AFP) biomarker. We found that all the studied biomarkers in our study have better sensitivity and specificity than AFP, when used separately or combined, at the diagnosis of early-stage HCC.
We could use the autophagy pathway biomarkers in the early-stage HCC diagnosis.
More autophagy biomarkers could be examined using first in silico analysis then clinical laboratory confirmation. Combining computational and clinical validations in clinical studies could benefit the research process immensely.