Cancer Medicine (Sep 2021)

Integrated pan‐cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance

  • Noushin Miralaei,
  • Ahmad Majd,
  • Kamran Ghaedi,
  • Maryam Peymani,
  • Masoomeh Safaei

DOI
https://doi.org/10.1002/cam4.4161
Journal volume & issue
Vol. 10, no. 18
pp. 6428 – 6441

Abstract

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Abstract Introduction The AURKA gene encodes a protein kinase involved in cell cycle regulation and plays an oncogenic role in many cancers. The main objective of this study is to analyze AURKA expression in 13 common cancers and its role in prognostic and drug resistance. Method Using the cancer genome atlas (TCGA) as well as CCLE and GDSC data, the level of AURKA gene expression and its role in prognosis and its association with drug resistance were evaluated, respectively. In addition, the expression level of AURKA was assessed in colorectal cancer (CRC) and gastric cancer (GC) samples. Besides, using Gene Expression Omnibus (GEO) data, drugs that could affect the expression level of this gene were also identified. Results The results indicated that the expression level of AURKA gene in 13 common cancers increased significantly compared to normal samples or it survived poorly (HR >1, p < 0.01) in lung, prostate, kidney, bladder, and uterine cancers. Also, the gene expression data showed increased expression in CRC and GC samples compared to normal ones. The level of AURKA was significantly associated with the resistance to SB 505124, NU‐7441, and irinotecan drugs (p < 0.01). Eventually, GEO data showed that JQ1, actinomycin D1, and camptothecin could reduce the expression of AURKA gene in different cancer cell lines (logFC < 1, p < 0.01). Conclusion Increased expression of AURKA is observed in prevalent cancers and associated with poor prognostic and the development of drug resistance. In addition, some chemotherapy drugs can reduce the expression of this gene.

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