Molecular Insights: Gene Expression in HCC and Testicular Cancer among ALD Patients.

• Hooriya Fatima

  Institute of Zoology, University of the Punjab, Quaid-i-Azam Campus, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0009-0002-7414-2098

• Humayoun H. Maqbool

  Institute of Zoology, University of the Punjab, Quaid-i-Azam Campus, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0000-0001-5225-7471

• Husna Ahmad

  Institute of Zoology, University of the Punjab, Quaid-i-Azam Campus, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0000-0003-4160-5148

• Nadeem Sheikh

  Institute of Zoology, University of the Punjab, Quaid-i-Azam Campus, Lahore, 54590, Pakistan

  Author

  https://orcid.org/0000-0001-9503-9538

Background: Alcohol-associated liver disease (ALD) leads to anomalies of hepatocellular carcinoma (HCC), and steatohepatitis. Though tremendous efforts have been made during the past 2 decades, ALD pathogenesis remains obscure. Currently, computational data analysis related to the residues of ALD patients is not widely emphasized, so most attention is needed on differentially expressed genes associated with HCC.

Methodology: A comparison between GSM4194985 (Healthy) and GSM4194987 (ALD) was conducted through the GEO database with the accession ID GSE141100 in the form of Raw RNA counts.  IDEP analyzed data through bicluster heatmaps for upregulated and downregulated genes for potential effects of ALD on the patients followed by pathway analysis through Reactome.

Results: The study revealed the downregulated expression of KCNK15 alongside the upregulation of MLXIPL and ART4 owing to ALD discerning their progression in HCC. As KCNK15 and MLXIPL both are involved in metabolism, their pathway analysis alleged the dysregulation of ion and insulin homeostasis respectively could lead to the progression of HCC.  ADH1B downregulation raises the possibility of poor alcohol metabolism, which exacerbates liver damage. Dysregulation of MLXIPL, KCNK15, and ART4 may accelerate the development of HCC. Furthermore, this study suggests that impaired spermatogenesis in ALD patients is associated with overexpression of C5orf58, KCNE1, and AKAP3.

Conclusion: This study reveals the inclination of developing HCC in ALD patients based on the differential expression of KCNK15, MLXIPL, and ART4 genes and liver toxicity by ADH1B. The upregulation of C5orf58, KCNE1, and AKAP3 may lead to the defective spermatogenesis that may contribute to the development of testicular cancer owing to the upregulation of C5orf58, KCNE1, and AKAP3 in spermatogenesis.

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