Predictive Value of Immune-Inflammatory Indices in Epithelial Ovarian Cancer

Öz

Objective: This study aimed to evaluate the prognostic significance of systemic immune-inflammatory indices, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in patients with epithelial ovarian cancer (EOC). Material and Methods: A retrospective analysis was conducted in patients with EOC diagnosed at Akdeniz University Hospital between 2005 and 2019. Patients with hematologic malignancies, autoimmune disorders, chronic inflammatory diseases, or a history of other cancers were excluded. Preoperative and postoperative hematologic parameters were recorded. The prognostic value of immune-inflammatory indices was assessed using nn-Meier survival analysis, Cox regression, and receiver operating characteristic (ROC) analysis. Results: A total of 264 EOC patients were included. Postoperative SII and NLR values were significantly higher than the preoperative levels (p<0.001). Higher postoperative SII and NLR were associated with serous histology, malignant cytology, and advanced-stage disease. ROC analysis showed that postoperative SII predicted omental metastasis (AUC=0.654, p<0.001), advanced-stage disease (AUC=0.641, p<0.001), and 3-year survival (AUC=0.663, p<0.001). Kaplan-Meier analysis revealed shorter overall survival in patients with high postoperative SII and NLR (p<0.001). Multivariate Cox regression confirmed that high postoperative SII (HR=2.45, p<0.001) and NLR (HR=1.89, p=0.001) as independent prognostic factors. Conclusion: Postoperative immune-inflammatory indices, particularly SII and NLR, are significant prognostic markers in EOC. Their association with advanced disease and poor survival highlights their potential clinical utility. Further studies are needed to confirm these findings.

Anahtar Kelimeler

• Epithelial ovarian cancer
• systemic immune-inflammation index
• neutrophil-to-lymphocyte ratio
• platelet-to-lymphocyte ratio
• prognosis
• survival

Epitelyal Over Kanserinde İmmün-İnflamatuar İndekslerin Prediktif Önemi

Öz

Amaç: Bu çalışmada epitelyal over kanseri (EOC) hastalarında sistemik immün-inflamasyon indeksi (SII), nötrofil-lenfosit oranı (NLR) ve trombosit-lenfosit oranı (PLR) gibi sistemik immün-inflamatuar indekslerin prognostik öneminin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Akdeniz Üniversitesi Hastanesi'nde 2005-2019 yılları arasında tanı konulan EOC hastaları üzerinde retrospektif bir analiz yapıldı. Hematolojik maligniteleri, otoimmün hastalıkları, kronik inflamatuar hastalıkları olan veya başka kanser öyküsü bulunan hastalar çalışmadan dışlandı. Ameliyat öncesi ve sonrası hematolojik parametreler toplandı. İmmün-inflamatuar indekslerin prognostik değeri Kaplan-Meier sağkalım analizi, Cox regresyonu ve alıcı işletim karakteristiği (ROC) analizi kullanılarak değerlendirildi. Bulgular: Toplam 264 EOC hastası çalışmaya dahil edildi. Ameliyat sonrası SII ve NLR değerleri ameliyat öncesine göre anlamlı derecede yüksekti (p<0.001). Ameliyat sonrası yüksek SII ve NLR değerleri seröz histoloji, malign sitoloji ve ileri evre hastalık ile ilişkiliydi. ROC analizi postoperatif SII'nin omental metastazı (AUC=0.654, p<0.001), ileri evre hastalığı (AUC=0.641, p<0.001) ve 3 yıllık sağ kalımı (AUC=0.663, p<0.001) öngördüğünü göstermiştir. Kaplan-Meier analizi, ameliyat sonrası SII ve NLR değeri yüksek olan hastalarda genel sağ kalımın daha az olduğunu göstermiştir (p<0.001). Çok değişkenli Cox regresyonu, yüksek postoperatif SII (HR=2.45, p<0.001) ve NLR'nin (HR=1.89, p=0.001) bağımsız prognostik faktörler olduğunu doğruladı. Sonuç: Ameliyat sonrası immün-inflamatuar indeksler, özellikle SII ve NLR, EOC'de önemli prognostik belirteçlerdir. İlerlemiş hastalık ve kötü sağ kalım ile olan ilişkileri, potansiyel klinik faydalarını vurgulamaktadır. Bu bulguları doğrulamak için daha ileri çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Epitelyal over kanseri
• sistemik immün-inflamasyon indeksi
• nötrofil-lenfosit oranı
• trombosit-lenfosit oranı
• prognoz
• sağkalım

Kaynakça

1. Robboy SJ. Robboy's pathology of the female reproductive tract: Elsevier Health Sciences; 2009.
2. Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nature reviews Disease primers. 2016;2(1):1-22.
3. Kucukgoz Gulec U, Gumurdulu D, Guzel AB, Paydas S, Seydaoglu G, Acikalin A, Khatib G, Zeren H, Vardar MA, Altintas A. Prognostic importance of survivin, Ki-67, and topoisomerase IIα in ovarian carcinoma. Archives of gynecology and obstetrics. 2014;289:393-8.
4. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-99.
5. Hu B, Yang X-R, Xu Y, Sun Y-F, Sun C, Guo W, Zhang X, Wang W-M, Qiu S-J, Zhou J. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clinical Cancer Research. 2014;20(23):6212-22.
6. Kargın S, Çakır M, Gündeş E, Yavuz Y, Esen HH, İyisoy MS, Kökbudak N, Küçükkartallar T. Relationship of preoperative neutrophil lymphocyte ratio with prognosis in gastrointestinal stromal tumors. Turkish Journal of Surgery/Ulusal cerrahi dergisi. 2015;31(2):61.
7. Chen L, Zhang F, Sheng X-g, Zhang S-q, Chen Y-t, Liu B-w. Peripheral platelet/lymphocyte ratio predicts lymph node metastasis and acts as a superior prognostic factor for cervical cancer when combined with neutrophil: Lymphocyte. Medicine. 2016;95(32):e4381.
8. Temur I, Gulec UK, Paydas S, Guzel AB, Sucu M, Vardar MA. Prognostic value of pre-operative neutrophil/lymphocyte ratio, monocyte count, mean platelet volume, and platelet/lymphocyte ratio in endometrial cancer. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2018;226:25-9.

9. Nie D, Gong H, Mao X, Li Z. Systemic immune-inflammation index predicts prognosis in patients with epithelial ovarian cancer: a retrospective study. Gynecologic Oncology. 2019;152(2):259-64.
10. Moses K, Brandau S, editors. Human neutrophils: their role in cancer and relation to myeloid-derived suppressor cells. Seminars in immunology; 2016: Elsevier.
11. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? The lancet. 2001;357(9255):539-45.
12. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer cell. 2011;20(5):576-90.
13. Yılmaz A, Tekin S, Bilici M, Yılmaz H. Clinical significance of inflammatory indexes in patients with epithelial ovarian cancer. Acta Oncol Tur. 2020;53(3):402-9.
14. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. New England journal of medicine. 2003;348(3):203-13.
15. Leffers N, Gooden MJ, de Jong RA, Hoogeboom B-N, ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunology, Immunotherapy. 2009;58:449-59.
16. Minardi D, Scartozzi M, Montesi L, Santoni M, Burattini L, Bianconi M, Lacetera V, Milanese G, Cascinu S, Muzzonigro G. Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer. Springerplus. 2015;4:1-5.
17. Chan JC, Chan DL, Diakos CI, Engel A, Pavlakis N, Gill A, Clarke SJ. The lymphocyte-to-monocyte ratio is a superior predictor of overall survival in comparison to established biomarkers of resectable colorectal cancer. Annals of surgery. 2017;265(3):539-46.
18. Huang Y, Chen Y, Zhu Y, Wu Q, Yao C, Xia H, Li C. Postoperative systemic immune-inflammation index (SII): a superior prognostic factor of endometrial cancer. Frontiers in Surgery. 2021;8:704235.
19. Kovács AR, Sulina A, Kovács KS, Lukács L, Török P, Lampé R. Prognostic significance of preoperative NLR, MLR, and PLR values in predicting the outcome of primary cytoreductive surgery in serous epithelial ovarian cancer. Diagnostics. 2023;13(13):2268.