Investigation of Serum Folate-Receptor-1 Levels in Patients with Non-Small Cell Lung Cancer

Abstract

Objective: Histopathological overexpression of folate receptor-1 (FOLR1) involved in folate transport in cell growth has been reported in various cancers. Increased serum FOLR1(sFOLR1) has also been reported in epithelial ovarian cancer. The aim was to investigate sFOLR1 levels in non-small cell lung cancer (NSCLC) patients and the response prediction of the standard chemotherapy targeting folic acid metabolism. Method: In this prospective study, sFOLR1 levels were investigated in 30 healthy individuals and 60 patients with stage4 malign metastatic NSCLC before and after standard chemotherapy. The commercial immunoassay (ELISA) kit used for analysis of sFOLR1. Serum carcinoembryonic antigen (CEA), vitamin B12, and folate levels were also investigated. Result: In NSCLC patients sFOLR1 levels were significantly higher(p<0.001) than the healthy individuals. After 3 months of standard treatment, sFOLR1 was significantly lower in patients(p<0.001). Diagnostic accuracy was strong in the differentiation of NSCLC patients from healthy individuals (AUC= 0.966). with the cut-off point of 82.45 pg/ml, the sFOLR1 level was performed with 95% sensitivity and 99% specificity. Pretreatment sFOLR1 levels were significantly lower in patients with-response to standard chemotherapy(p<0.01). The best predictive value was determined as 393.80 pg/ml. At the end of the 401 days, a significant difference found in patients with high the sFOLR1 predictive value. The median overall survival (OS) duration was 288 days for all patients (95% GA 198.13-377.87). Median progression-free survival (PFS) was 321 days (95% GA 211.90-430.10). Conclusion: For monitoring standard chemotherapy with drugs targeting folic acid metabolism, sFOLR-1 levels may be important biomarker.

Keywords

• Folate receptor 1
• biomarker
• Nonsmall cell lung cancer
• chemotherapy
• carcinoembryonic antigen

Küçük Hücreli Dışı Akciğer Kanserli Hastalarda Serum Folat-Reseptör-1 Düzeylerinin Araştırılması

Abstract

Amaç: Hücre büyümesinde folat taşınmasında rol oynayan folat reseptörü-1'in (FOLR1) histopatolojik aşırı ekspresyonu çeşitli kanserlerde bildirilmiştir. Artmış serum FOLR1(sFOLR1) epitelyal yumurtalık kanserinde de rapor edilmiştir. Amaç, küçük hücreli dışı akciğer kanseri (KHDAK) hastalarında sFOLR1 düzeylerini ve folik asit metabolizmasını hedefleyen standart kemoterapinin tahminini yanıtını araştırmaktı. Gereç ve Yöntem: Bu prospektif çalışmada, standart kemoterapi öncesi ve sonrası evre4 malign metastatik KHDAK'li 60 hasta ve 30 sağlıklı bireyde sFOLR1 düzeyleri araştırıldı. Ticari immünolojik test (ELISA) kiti sFOLR1'in analizi için kullanıldı. Serum karsinoembriyonik antijen (CEA), vitamin B12 ve folat düzeyleri de araştırıldı. Bulgular: KHDAK hastalarında sFOLR1 seviyeleri sağlıklı bireylere göre anlamlı derecede yüksekti(p<0,001). 3 aylık standart tedaviden sonra hastalarda sFOLR1 anlamlı olarak daha düşüktü (p<0,001). KHDAK hastalarının sağlıklı bireylerden ayırt edilmesinde tanısal doğruluk güçlüydü (AUC= 0.966). Tanısal doğruluk sFOLR1 seviyesi 82.45 pg/ml kesme noktasında %95 duyarlılık ve %99 özgüllük gerçekleştirmiştir. Standart kemoterapiye yanıt veren hastalarda tedavi öncesi sFOLR1 düzeyleri anlamlı olarak daha düşüktü(p<0.01). En iyi tahmin değeri 393.80 pg/ml olarak belirlendi. 401 günün sonunda sFOLR1 tahmin değeri yüksek olan hastalarda anlamlı fark bulundu. Medyan genel sağkalım (OS) süresi tüm hastalar için 288 gündü (%95 GA 198.13-377.87). Medyan progresyonsuz sağkalım (PFS) 321 gündü (%95 GA 211.90-430.10). Sonuç: Folik asit metabolizmasını hedefleyen ilaçlarla standart kemoterapiyi izlemek için sFOLR-1 seviyeleri önemli bir biyobelirteç olabilir.

Keywords

• Folat Reseptörü 1 (FOLR1)
• Karsinoembriyonik Antijen (CEA)
• Küçük Hücreli Olmayan Akciğer Kanseri (KHDAK)
• Kemoterapi
• Biyobelirteç

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