Elevated Serum Tumor Markers (HE4 and ROMA Score) and Increased Treg Cells Distinguished Ovarian Cancer and Benign Tumor

Manuel Hutapea, Syamsudin Syamsudin, Iin Kurnia, Miswar Fattah, Ujang Saeful Hikmat, Vinessa Gracia Putri

Abstract


BACKGROUND: Tumor markers such as human epididymis protein 4 (HE4), cancer antigen 125 (CA-125), and risk of ovarian malignancy algorithm (ROMA) are frequently utilized for diagnostic and prognostic purposes. Lymphocytes, essential immune cells, play a significant role in eliminating cancer cells. However, the precise correlation between tumor markers and lymphocytes remains incompletely elucidated. The aim of this study was to explore the correlation between tumor markers and lymphocyte subtype profiles in differentiating ovarian cancer and benign tumors.

METHODS: This was a cross-sectional study involving 12 ovarian cancer and 17 benign ovarian tumor patients. Blood samples were collected for the characterization of T lymphocytes, B lymphocytes, natural killer (NK), and T regulatory (Treg), which were analyzed using flowcytometry. Additionally, tumor markers HE4 and CA-125 were measured from patient serum using the chemiluminescent microparticle immunoassay (CMIA) method.

RESULTS: Benign ovarian tumors and ovarian cancer can be distinguished by a significant increase in HE4 levels (p=0.004), ROMA (p=0.004), and Treg cells (CD4+/CD25+/FOXP3+, p=0.017). Furthermore, the correlation between tumor markers and lymphocytes indicates that an increase in ROMA was weakly correlated with an increase in the percentage of T regulatory cells (CD4+/CD25+/FOXP3+, r=0.553, p=0.006) and B lymphocytes (CD19+, r=0.528, p=0.010), accompanied by a decrease in the number of T lymphocytes (CD3+, r=-0.598, p=0.003), T helper lymphocytes (CD3+CD4+, r=-0.594, p=0.003), and cytotoxic lymphocytes (CD3+CD8+, r=-0.510, p=0.013).

CONCLUSION: The elevation of serum tumor markers (HE4 and ROMA) accompanied by an increase in Treg cells can distinguish between benign ovarian tumor patients and ovarian cancer patients.

KEYWORDS: tumor marker, CA-125, HE4, ROMA, subtype of lymphocytes, ovarian cancer


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References


Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: A review. Cancer Biol Med. 2017; 14(1): 9-32, CrossRef.

Evans DG, Wisely J, Clancy T, Lalloo F, Wilson M, Johnson R, et al. Longer term effects of the Angelina Jolie effect: increased risk-reducing mastectomy rates in BRCA carriers and other high-risk women. Breast Cancer Res. 2015; 17: 143, CrossRef.

Prayudi PKA, Winata IGS, Budiana ING, Saspriyana KY, Mahendra INB, Suwiyoga K. Preoperative Level of insulin-like growth factor binding protein 2 predicts the suboptimal outcome after primary debulking surgery in patients with advance ovarian cancer. Indones Biomed J. 2023; 15(6): 429-36, CrossRef.

Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (Suppl 6): vi24-32, CrossRef.

Yuane E, Dewanto A, Widad S. High expression of PR-A and low expression of PR-B is correlated with inflammation in endometrioma cases. Indones Biomed J. 2023; 15(1): 85-93, CrossRef.

Van Gorp T, Cadron I, Despierre E, Daemen A, Leunen K, Amant F, et al. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer. 2011; 104(5): 863-70, CrossRef.

Ahmed AA, Abdou AM. Diagnostic accuracy of CA125 and HE4 in ovarian carcinoma patients and the effect of confounders on their serum levels. Curr Probl Cancer. 2019; 43(5): 450-60, CrossRef.

Scholler N, Urban N. CA125 in ovarian cancer. Biomark Med. 2007; 1(4): 513-23, CrossRef.

Muhammad S, Antonius PA, Oktavian R, Savannah A. Rapidly growing ovarian granulosa cell tumor following complete debulking for suspected ovarian cancer with histopathology result of benign ovarian cyst. Mol Cell Biomed Sci. 2023; 7(3): 162-7, CrossRef.

Hertlein L, Stieber P, Kirschenhofer A, Krocker K, Nagel D, Lenhard M, et al. Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med. 2012; 50(12): 2181-8, CrossRef.

Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020; 30(16): R921-5, CrossRef.

Oltean T, Lippens L, Lemeire K, De Tender C, Vuylsteke M, Denys H, et al. Association of cell death markers with tumor immune cell infiltrates after chemo-radiation in cervical cancer. Front Oncol. 2022; 12: 892813, CrossRef.

Zhang L, Zhang H, Huang Y, Xi X, Sun Y. Expression of immune cell markers and tumor markers in patients with cervical cancer. Int J Gynecol Cancer. 2020; 30(7): 969-74, CrossRef.

James NE, Oliver MT, Ribeiro JR, Cantillo E, Rowswell-Turner RB, Kim KK, et al. Human epididymis secretory protein 4 (HE4) compromises cytotoxic mononuclear cells via inducing dual specificity phosphatase 6. Front Pharmacol. 2019; 10: 216, CrossRef.

Anastasi E, Farina A, Granato T, Colaiacovo F, Pucci B, Tartaglione S, et al. Recent insight about HE4 role in ovarian cancer oncogenesis. Int J Mol Sci. 2023; 24(13): 10479, CrossRef.

Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008; 31(6): 681-90, CrossRef.

Bast RC Jr., Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981; 68(5): 1331-7, CrossRef.

Hawkins RE, Roberts K, Wiltshaw E, Mundy J, McCready VR. The clinical correlates of serum CA125 in 169 patients with epithelial ovarian carcinoma. Br J Cancer. 1989; 60(4): 634-7, CrossRef.

Lawrie TA, Winter-Roach BA, Heus P, Kitchener HC. Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer. Cochrane Database Syst Rev. 2015; 2015(12): Cd004706, CrossRef.

Krivak TC, Tian C, Rose GS, Armstrong DK, Maxwell GL. A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage III optimally debulked ovarian cancer treated with intraperitoneal compared to intravenous chemotherapy: an analysis of patients enrolled in GOG 172. Gynecol Oncol. 2009; 115(1): 81-5, CrossRef.

Juretzka MM, Barakat RR, Chi DS, Iasonos A, Dupont J, Abu-Rustum NR, et al. CA125 level as a predictor of progression-free survival and overall survival in ovarian cancer patients with surgically defined disease status prior to the initiation of intraperitoneal consolidation therapy. Gynecol Oncol. 2007; 104(1): 176-80, CrossRef.

Cannistra SA. Cancer of the ovary. N Engl J Med. 2004; 351(24): 2519-29, CrossRef.

Rodriguez GM, Galpin KJC, McCloskey CW, Vanderhyden BC. The tumor microenvironment of epithelial ovarian cancer and its influence on response to immunotherapy. Cancers. 2018; 10(8): 242, CrossRef.




DOI: https://doi.org/10.18585/inabj.v16i3.3027

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