The Role of Akt2 and CA-125 Serum Levels as Predictors for Successful Cytoreduction in Epithelial Ovarian Cancer Surgery

Ovarian cancer is one of the common causes of cancer deaths in gynecological malignancies in Indonesia, and indeed the world. Of all classifications of ovarian cancer, the epithelial subtype shows the highest incidence. Cytoreductive surgery is a determinant of prognosis for patients with advanced epithelial ovarian cancer. One possible way to predict the results of cytoreductive surgery is to measure preoperative tumor marker levels. This study aimed to assess the validity of serum levels of Protein kinase Bβ (Akt2) and cancer antigen-125 (CA-125) as outcome predictors for cytoreduction in epithelial ovarian cancer surgery. This was an observational, analytical, cross-sectional study. Akt2 and CA-125 serum levels were examined by enzyme-linked immunosorbent assay (ELISA) and immunoassay technique, respectively. Mean levels of Akt2 and CA-125 were significantly different between optimal and suboptimal cytoreduction groups (p < 0.05). The cut-off point (COP) value obtained for Akt2 was 1.20 U/mL with area under curve (AUC) value of 68.9%, while the COP for CA-125 was 222.50 U/mL with AUC value of 75.3 % (p < 0.05). If the preoperative Akt2 serum level was greater than 1.20 U/mL, and preoperative CA-125 level was greater than 222.5 U/mL, the probability of suboptimal cytoreduction was increased. Thus, our study highlights the possibility for Akt2 and CA-125 levels to be used as serum biomarkers in predicting the success of cytoreductive surgery.

Epithelial ovarian cancer; cytoreduction; Akt2; CA-125.

[1] WHO. GLOBOCAN (2012): Estimated Cancer Incidence, Mor-tality, and Prevalence Worldwide in 2012 v1.0 [Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx].

[2] Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A. and Jemal A.: “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries”. Ca. Cancer J. Clin., 2018, 68, 394-424.

[3] Berek J.S., Friedlander M.L., Bast R.C.: “Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer”. Holland-Frei Cancer Medicine, 2017, 65, 1-27.

[4] Berek J.S.: “Ovarian Cancer”. Hacker &Amp;Amp Moore’s Essentials of Obstetrics and Gynecology, 2010, 412-419.

[5] Morgan R.J., Armstrong D.K., Alvarez R.D., Bakkum-Gamez J.N., Behbakht K., Chen L-M, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Ovarian cancer, including fal-lopian tube cancer and primary peritoneal cancer: NCCN.org 2015 [Available from: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf].

[6] Prat J. The International Federation of Gynecologists and Ob-stetricians. New FIGO ovarian cancer staging guidelines 2014 [Available from: https://www.sgo.org/clinical-practice/guidelines/new-figo-ovarian-cancer-staging-guidelines/].

[7] Saitou M., Iida Y., Komazaki H., Narui C., Matsuno K., Kawa-bata A., et al.: “Success rate and safety of tumor debulking with diaphragmatic surgery for advanced epithelial ovarian cancer and peritoneal cancer”. Arch. Gynecol. Obstet., 2015, 291, 641-646.

[8] Arab M., Jamdar F., Sadat Hosseini M., Ghodssi- Ghasemabadi R., Farzaneh F., Ashrafganjoei T.: “Model for Prediction of Optimal Debulking of Epithelial Ovarian Cancer”. Asian Pacific Journal of Cancer Prevention: APJCP, 2018, 191319-1324.

[9] Suidan R.S., Ramirez P.T., Sarasohn D.M., Teitcher J.B., Mironov S., Iyer R.B., et al.: “A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer”. Gynecol. Oncol., 2014, 134, 455-461.

[10] Comamala M., Pinard M., Thériault C., Matte I., Albert A., Boivin M., et al.: “Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells”. Br. J. Cancer, 2011, 104, 989-999.

[11] Barron C.C., Bilan P.J., Tsakiridis T., Tsiani E.: “Facilitative glu-cose transporters: Implications for cancer detection, prognosis and treatment”. Metabolism, 2016, 65, 124-139.

[12] Menczer J., Ben-Shem E., Golan A., Levy T.: “The Significance of Normal Pretreatment Levels of CA125 (< 35 U/mL) in Epithelial Ovarian Carcinoma”. Rambam Maimonides Medical Journal, 2015, 6, e0005.

[13] Zheng B., Geng L., Zeng L., Liu F., Huang Q.: “AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3NF-κB axis”. Cell. Signal., 2018, 45, 122-131.

[14] Linnerth-Petrik N.M., Santry L. A., Moorehead R., Jücker M., Wootton S.K., Petrik J.: “Akt isoform specific effects in ovarian cancer progression”. Oncotarget, 2016, 7, 74820-74833.

[15] Cai J., Xu L., Tang H., Yang Q., Yi X., Fang Y., et al.: “The Role of the PTEN/PI3K/Akt Pathway on Prognosis in Epithelial Ovarian Cancer: A Meta‐Analysis”. the Oncologist, 2014, 19, 528-535.

[16] Sehouli J., Grabowski J.P.: “Surgery for recurrent ovarian cancer: Options and limits”. Best Practice & Research Clinical Obstetrics & Gynaecology, 2017, 41, 88-95.

[17] Chesnais M., Lecuru F., Mimouni M., Ngo C., Fauconnier A., Hu-chon C.: “A preoperative predictive score to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer”. Plos one, 2017, 12, e0187245.

[18] Feng L., Liao S., Li L.: “Preoperative serum levels of HE4 and CA125 predict primary optimal cytoreduction in advanced epithelial ovarian cancer: a preliminary model study”. J. Ovarian Res., 2020, 13.

[19] Zeng J., Yin J., Song X., Jin Y., Li Y., Pan L.: “Reduction of CA125 Levels During Neoadjuvant Chemotherapy Can Predict Cytoreduction to No Visible Residual Disease in Patients with Advanced Epithelial Ovarian Cancer, Primary Carcinoma of Fallopian tube and Peritoneal Carcinoma”. Journal of Cancer, 2016, 7, 2327-2332.

[20] Kim S.J., Rosen B., Fan I., Ivanova A., McLaughlin J. R., Risch H., et al.: “Epidemiologic factors that predict long-term survival following a diagnosis of epithelial ovarian cancer”. Br. J. Cancer, 2017, 116, 964-971.

[21] Purcell S.A., Elliott S.A., Kroenke C.H., Sawyer M.B., Prado C.M.: “Impact of Body Weight and Body Composition on Ovarian Cancer Prognosis”. Curr. Oncol. Rep., 2016, 18, 8.