The Frequency of the v-AKT Murine Thymoma Viral Oncogene Homologue 1 Gene Amplification among Sudanese Women with Ovarian Cancer: A Cross-Sectional Study
Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge,
there is a lack of published reports about the amplification of the genes belonging
to the AKT family among Sudanese women with
OC. The present study was conducted to detect the AKT1 gene amplification and
its association with tumour types, grades, and ages among Sudanese women
with OC, bearing in mind the ethnic variation. Methods: This
institution-based study included 79 cases of women diagnosed with ovarian
cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018.
Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract
RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results:
The mean age (±SD) of included women was 49.29
(±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11
(27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC
(16.7%). High frequency was seen in women with low (26.3%; n = 10/28) rather
than in higher (19.5%; n = 8/33) grade carcinoma, and in older (25.8%; n =
8/23) rather than younger (18.2%; n= 2/9) women. No significant association between
AKT1 gene amplification and tumour types, grades, and ages of women was
observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion:
AKT1 gene amplification arises in around one-fifth of Sudanese women with
ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and
mucinous tumours types, and more frequently in low tumour grade and older
women, but not to a statistically significant level. These outcomes sustenance
previous studies suggesting that activated AKT genes have a vital role in OC
progression and may offer a plan for targeted therapy and prognostic
evaluation.
References
[1]
Gong, J., et al. (2019) L-Tetrahydropalmatine Enhances the Sensitivity of Human Ovarian Cancer Cells to Cisplatin via microRNA-93/PTEN/Akt Cascade. Journal of BUON: Official Journal of the Balkan Union of Oncology, 24, 701-708.
[2]
Liu, Z., et al. (2019) Inhibition of Ca2+-Activated Chloride Channel ANO1 Suppresses Ovarian Cancer through Inactivating PI3K/Akt Signaling. International Journal of Cancer, 144, 2215-2226. https://doi.org/10.1002/ijc.31887
[3]
Shen, F., et al. (2019) CEMIP Promotes Ovarian Cancer Development and Progression via the PI3K/AKT Signaling Pathway. Biomedicine & Pharmacotherapy, 114, Article ID: 108787. https://doi.org/10.1016/j.biopha.2019.108787
[4]
Majem, B., et al. (2019) MicroRNA-654-5p Suppresses Ovarian Cancer Development Impacting on MYC, WNT and AKT Pathways. Oncogene, 38, 6035-6050. https://doi.org/10.1038/s41388-019-0860-0
[5]
Wu, Y.-H., et al. (2019) Akt Inhibitor SC66 Promotes Cell Sensitivity to Cisplatin in Chemoresistant Ovarian Cancer Cells through Inhibition of COL11A1 Expression. Cell Death & Disease, 10, 322. https://doi.org/10.1038/s41419-019-1555-8
[6]
Zheng, B., et al. (2018) AKT2 Contributes to Increase Ovarian Cancer Cell Migration and Invasion through the AKT2-PKM2-STAT3/NF-κB Axis. Cellular Signalling, 45, 122-131. https://doi.org/10.1016/j.cellsig.2018.01.021
[7]
Song, M., et al. (2019) AKT as a Therapeutic Target for Cancer. Cancer Research, 79, 1019-1031. https://doi.org/10.1158/0008-5472.CAN-18-2738
[8]
Shariati, M. and Meric-Bernstam, F. (2019) Targeting AKT for Cancer Therapy. Expert Opinion on Investigational Drugs, 28, 977-988. https://doi.org/10.1080/13543784.2019.1676726
[9]
Revathidevi, S. and Munirajan, A.K. (2019) Akt in Cancer: Mediator and More. Seminars in Cancer Biology, 59, 80-91. https://doi.org/10.1016/j.semcancer.2019.06.002
[10]
Cole, P.A., et al. (2019) AKTivation Mechanisms. Current Opinion in Structural Biology, 59, 47-53. https://doi.org/10.1016/j.sbi.2019.02.004
[11]
Owusu-Brackett, N., Shariati, M. and Meric-Bernstam, F. (2019) Role of PI3K/AKT/ mTOR in Cancer Signaling. In: Badve, S. and Kumar, G.L., Eds., Predictive Biomarkers in Oncology, Springer, Berlin, 263-270. https://doi.org/10.1007/978-3-319-95228-4_20
[12]
Ediriweera, M.K., Tennekoon, K.H. and Samarakoon, S.R. (2019) Role of the PI3K/AKT/mTOR Signaling Pathway in Ovarian Cancer: Biological and Therapeutic Significance. Seminars in Cancer Biology, 59, 147-160. https://doi.org/10.1016/j.semcancer.2019.05.012
[13]
Shi, X., et al. (2019) Research Progress on the PI3K/AKT Signaling Pathway in Gynecological Cancer. Molecular Medicine Reports, 19, 4529-4535. https://doi.org/10.3892/mmr.2019.10121
[14]
Wang, J., et al. (2018) AKT Isoform-Specific Expression and Activation across Cancer Lineages. BMC Cancer, 18, 742. https://doi.org/10.1186/s12885-018-4654-5
[15]
Saura, C., et al. (2017) A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors. Cancer Discovery, 7, 102-113. https://doi.org/10.1158/2159-8290.CD-16-0512
[16]
Abubaker, J., et al. (2009) PIK3CA Alterations in Middle Eastern Ovarian Cancers. Molecular Cancer, 8, 51. https://doi.org/10.1186/1476-4598-8-51
[17]
Livak, K.J. and Schmittgen, T.D. (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCT Method. Methods, 25, 402-408. https://doi.org/10.1006/meth.2001.1262
[18]
Linnerth-Petrik, N.M., et al. (2016) Akt Isoform Specific Effects in Ovarian Cancer Progression. Oncotarget, 7, 74820-74833. https://doi.org/10.18632/oncotarget.11204
[19]
Bell, D., et al. (2011) Integrated Genomic Analyses of Ovarian Carcinoma. Nature, 474, 609-615. https://doi.org/10.1038/nature10166
[20]
Etemadmoghadam, D. and Bowtell, D. (2014) AKT1 Gene Amplification as a Biomarker of Treatment Response in Ovarian Cancer: Mounting Evidence of a Therapeutic Target. Gynecologic Oncology, 135, 409-410. https://doi.org/10.1016/j.ygyno.2014.11.007
[21]
Kyung, H.Y. and Lauring, J. (2016) Recurrent AKT Mutations in Human Cancers: Functional Consequences and Effects on Drug Sensitivity. Oncotarget, 7, 4241-4251. https://doi.org/10.18632/oncotarget.6648
[22]
van de Stolpe, A. (2019) Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer. Cancers, 11, 293. https://doi.org/10.3390/cancers11030293
[23]
Carpten, J.D., et al. (2007) A Transforming Mutation in the Pleckstrin Homology Domain of AKT1 in Cancer. Nature, 448, 439-444. https://doi.org/10.1038/nature05933
[24]
Altomare, D.A., et al. (2004) AKT and mTOR Phosphorylation Is Frequently Detected in Ovarian Cancer and Can Be Targeted to Disrupt Ovarian Tumor Cell Growth. Oncogene, 23, 5853-5857. https://doi.org/10.1038/sj.onc.1207721
[25]
Hanrahan, A.J., et al. (2012) Genomic Complexity and AKT Dependence in Serous Ovarian Cancer. Cancer Discovery, 2, 56-67. https://doi.org/10.1158/2159-8290.CD-11-0170
