Ileri evre küçük hücreli dışı akciğer kanserinde, plazma vasküler endotelyal büyüme faktörleri ve trombosit faktör 4 düzeylerinin prognostik önemi ve sağkalım süreleri ile ilişkisi
Küçük Resim Yok
Tarih
2008
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İleri evre akciğer kanserli hastalarda mevcut tüm yeni tedavi modellerine karşın hastalığın kontrolü son derece zordur. Son yıllarda kanser tedavisi için yapılan araştırmalarda tümör çoğalması ve metastazının mekanizmalarının anlaşılması için uğraşılmakta ve bu mekanizmaları hedef alan tedaviler geliştirilmeye çalışılmaktadır. Bu nedenle tümörün damarlanma miktarı, damar oluşturma yeteneği ve in vivo ortamda anjiogenik ve antianjiogenik faktörlerin dengesinin bilinmesi gelecekte akciğer kanseri gibi tümörlerde yeni bir tedavi seçeneği gündeme getirecektir. Bu çalışmanın temel amacı; ileri evre küçük hücreli dışı akciğer kanserli hastalarda, tanı anındaki anjiogenik ve antianjiogenik moleküllerin plazma düzeylerinin ve anjiogenik antianjiogenik dengenin prognostik öneminin saptanmasıdır. Kasım 2005-Kasım 2007 tarihleri arasında Trakya Üniversitesi Tıp Fakültesi Göğüs Hastalıkları kliniğinde ileri evre küçük hücreli dışı akciğer kanseri tanısı alan 60 hasta ile 45 kişiden oluşan sağlıklı gönüllü bireyler çalışmaya alındı. Vasküler endotelyal büyüme faktörleri ve trombosit faktör-4 plazma düzeyleri ELİSA yöntemi ile ölçüldü. Sağkalım istatistiklerinde anlamlı çıkan parametrelerin ROC analizi ile duyarlılığı ve özgüllüğü en hassas olan eşik değeri belirlendi. Küçük hücreli dışı akciğer kanserli hastaların tanı anındaki Vasküler endotelyal büyüme faktörleri ve trombosit faktör-4 düzeyleri sağlıklı bireylere göre anlamlı olarak yüksek bulundu (p < 0.05). Trombositozu olan hastaların trombosit faktör-4 düzeyleri daha yüksekti (p < 0.05). Ortalama trombosit hacmi ?7.7 fl lökosit sayısı ?10.000 / mm3, LDH ? 240 IU/dl ve CRP ? 4 mg/dl olan hastaların Vasküler endotelyal büyüme faktörü-A düzeyleri daha yüksekti (p < 0.05). Hastaların ortalama yaşam süresi 238 ± 22 gündü (%95 GA, 194 – 283 gün). Hastalık evresi, lökosit sayısı, LDH ve CRP değerleri ile sağkalım süreleri arasında anlamlı ilişki vardı (p < 0.05). Vasküler endotelyal büyüme faktörü-C düzeyi ? 3 pg / ml olan hastaların ortalama sağkalım süresi 360 ± 51 gün, < 3 pg / ml olan hastaların 196 ± 21 gündü (p = 0.005) (duyarlılık %42, özgüllük %100). Trombosit faktör-4 düzeyi < 250 IU /mL olan hastaların ortalama sağkalım süresi 104 ± 14 gün, ? 250 IU /mL olan hastaların 295 ± 31 gündü (p < 0.001) (duyarlılık %84, özgüllük %63). Vasküler endotelyal büyüme faktörü-A düzeyi ? 240 pg /ml olan hastaların ortalama sağkalım süresi 239 ± 37 gün, < 240 pg / ml olan hastaların 296 ± 41 gündü (p > 0.05). Vasküler endotelyal büyüme faktörü-C / trombosit faktör-4 ? 1.2 olan hastaların ortalama sağkalım süresi 360 ± 51 gün < 1.2 olan hastaların 195 ± 23 gündü (p = 0.006) (duyarlılık %42, özgüllük %88). Vasküler endotelyal büyüme faktörü-C / Vasküler endotelyal büyüme faktörü-A ?1.25 olan hastaların sağkalım süresi 331 ± 43 gün, < 1.25 olan hastaların 188 ± 25 gündü (p = 0.007) Vasküler endotelyal büyüme faktörü-A / trombosit faktör-4 oranı < 0.8 olan hastaların ortalama sağkalım süresi 231 ± 35 gün, ? 0.8 olan hastaların 310 ± 47 gündü. (p > 0.05) (duyarlılık %46, özgüllük %94). Çalışmamızda p değeri anlamlı çıkan parametreler çok değişkenli analize alındı. Trombosit faktör-4 ve vasküler endotelyal büyüme faktörü-C / trombosit faktör-4 oranı bağımsız prognostik faktörler olarak saptandı. Sonuç olarak bu çalışma; ileri evre küçük hücreli dışı akciğer kanserli hastalarda tanı anındaki anjiogenik ve antianjiogenik moleküllerin plazma düzeylerinin ve anjiogenik antianjiogenik dengenin sağkalım sürelerini etkilediğini, VEGF-A 'nın akciğer kanserindeki inflamasyon ile doğru orantılı olarak arttığını ve bu durumun sağkalımı olumsuz etkilediğini, VEGF-C'nin genel görüşün aksine kanser üzerinde olumlu etkilerinin olduğunu, VEGF-A ve TF4'ün akciğer kanserindeki ana kaynağının trombositler olduğunu, TF4 ve VEGF-C / TF4 oranının küçük hücreli dışı akciğer kanserinde bağımsız prognostik faktörler olduğunu gösterdi. Anahtar kelimeler: Küçük hücreli dışı akciğer kanseri, anjiogenez, VEGF, TF4
In spite of new treatment modalities in advanced stage lung cancer, the control of disease activity is very difficult. Recent studies on cancer research have focused on tumour proliferation and mechanisms of metastasis; and drugs targeting these mechanisms have been being developed. Therefore, if the microvessel density of the tumour, its ability for angiogenesis, and the balance between angiogenic and antiangiogenic factors is known, new treatment choices for lung cancer might be possible. The main aim of this study was to detect the plasma levels of angiogenic and antiangiogenic molecules and the prognostic significance of the angiogenic/antiangiogenic balance in newly diagnosed advanced stage nosmall cell lung cancer patients. We included 60 advanced stage nonsmall cell lung cancer patients diagnosed at Trakya University Medical Faculty Department of Chest Diseases between November 2005- November 2007 and 45 voluntary healthy controls into our study. Plasma levels of VEGF-A, VEGF-C and TF4 were determined by ELISA. Threshold of each parameters which affect on overall survival use determined by waing ROC curve analysis. Nonsmall cell lung cancer patients had significantly higher levels of VEGF-A, VEGFC and TF4 than healthy controls at the time of diagnosis (p < 0.05). TF4 levels in patients with thrombocytosis were higher (p<0.05). Patients with mean platelet volume ?7.7 fl., leucocytes ?10.000 / mm3, LDH ? 240 IU/dl and CRP ? 4 mg/dl had higher VEGF-A levels (p < 0.05). The mean duration of survival for the patients was 238 ± 22 days (95% CI, 194-283 days). There was a significant association between disease stage, leucocyte count, LDH and CRP values and the duration of survival (p<0.05). The mean duration of survival for patients with VEGF-C levels ? 3 pg / ml was 360 ± 51 days, and for patients with levels < 3 pg / ml was 196 ± 21 days (p = 0.005) (sensitivity 42%, specificity 100%). For patients with TF4 levels < 250 IU /mL, the mean duration of survival was 104 ± 14 days, and for patients with levels ? 250 IU /mL, it was 295 ± 31 days (p < 0.001) (sensitivity 84%, specificity 63%). For patients with VEGF-A level ? 240 pg /ml, the mean duration of survival was 239 ± 37 days, and for patients with levels < 240 pg / ml it was 296 ± 41 days (p > 0.05). For patients with VEGF-C / TF4 ? 1.2, the mean duration of survival was 360 ± 51 days (p = 0.006), for patients with a ratio < 1.2 it was 195 ± 23 days (sensitivity 42%, specificity 88%). If VEGF-C / VEGF-A was ?1.25, the mean duration of survival was 331 ± 43 days; and if the ratio was < 1.25, it was 188 ± 25 days (p = 0.007). When VEGF-A / TF4 ratio was < 0.8, the mean duration of survival was 231 ± 35 days, and when the ratio was ? 0.8, it was 310 ± 47 days (p > 0.05) (sensitivity 46%, specificity 94%). When multivariate analysis for parameters with a significant p value was performed, it was seen that TF4 and VEGF-C / TF4 ratio were independantly prognostic parameters. As a result, this study demonstrated that the plasma levels of angiogenic and antiangiogenic molecules and the angiogenic vs. antiangiogenic balance at the time of diagnosis in advanced stage nonsmall cell lung cancer patients affect the duration of survival; VEGF-A increases in direct proportion to the inflammation in lung cancer and that this has negative influence on survival; VEGF-C has positive influence on cancer contrarily to the general consensus; the main source of VEGF-A and TF4 in lung cancer are platelets; TF4 and VEGF/TF4 ratio are independant prognostic parameters in lung cancer. Key words: Nonsmall cell lung cancer, angiogenesis, VEGF, TF4.
In spite of new treatment modalities in advanced stage lung cancer, the control of disease activity is very difficult. Recent studies on cancer research have focused on tumour proliferation and mechanisms of metastasis; and drugs targeting these mechanisms have been being developed. Therefore, if the microvessel density of the tumour, its ability for angiogenesis, and the balance between angiogenic and antiangiogenic factors is known, new treatment choices for lung cancer might be possible. The main aim of this study was to detect the plasma levels of angiogenic and antiangiogenic molecules and the prognostic significance of the angiogenic/antiangiogenic balance in newly diagnosed advanced stage nosmall cell lung cancer patients. We included 60 advanced stage nonsmall cell lung cancer patients diagnosed at Trakya University Medical Faculty Department of Chest Diseases between November 2005- November 2007 and 45 voluntary healthy controls into our study. Plasma levels of VEGF-A, VEGF-C and TF4 were determined by ELISA. Threshold of each parameters which affect on overall survival use determined by waing ROC curve analysis. Nonsmall cell lung cancer patients had significantly higher levels of VEGF-A, VEGFC and TF4 than healthy controls at the time of diagnosis (p < 0.05). TF4 levels in patients with thrombocytosis were higher (p<0.05). Patients with mean platelet volume ?7.7 fl., leucocytes ?10.000 / mm3, LDH ? 240 IU/dl and CRP ? 4 mg/dl had higher VEGF-A levels (p < 0.05). The mean duration of survival for the patients was 238 ± 22 days (95% CI, 194-283 days). There was a significant association between disease stage, leucocyte count, LDH and CRP values and the duration of survival (p<0.05). The mean duration of survival for patients with VEGF-C levels ? 3 pg / ml was 360 ± 51 days, and for patients with levels < 3 pg / ml was 196 ± 21 days (p = 0.005) (sensitivity 42%, specificity 100%). For patients with TF4 levels < 250 IU /mL, the mean duration of survival was 104 ± 14 days, and for patients with levels ? 250 IU /mL, it was 295 ± 31 days (p < 0.001) (sensitivity 84%, specificity 63%). For patients with VEGF-A level ? 240 pg /ml, the mean duration of survival was 239 ± 37 days, and for patients with levels < 240 pg / ml it was 296 ± 41 days (p > 0.05). For patients with VEGF-C / TF4 ? 1.2, the mean duration of survival was 360 ± 51 days (p = 0.006), for patients with a ratio < 1.2 it was 195 ± 23 days (sensitivity 42%, specificity 88%). If VEGF-C / VEGF-A was ?1.25, the mean duration of survival was 331 ± 43 days; and if the ratio was < 1.25, it was 188 ± 25 days (p = 0.007). When VEGF-A / TF4 ratio was < 0.8, the mean duration of survival was 231 ± 35 days, and when the ratio was ? 0.8, it was 310 ± 47 days (p > 0.05) (sensitivity 46%, specificity 94%). When multivariate analysis for parameters with a significant p value was performed, it was seen that TF4 and VEGF-C / TF4 ratio were independantly prognostic parameters. As a result, this study demonstrated that the plasma levels of angiogenic and antiangiogenic molecules and the angiogenic vs. antiangiogenic balance at the time of diagnosis in advanced stage nonsmall cell lung cancer patients affect the duration of survival; VEGF-A increases in direct proportion to the inflammation in lung cancer and that this has negative influence on survival; VEGF-C has positive influence on cancer contrarily to the general consensus; the main source of VEGF-A and TF4 in lung cancer are platelets; TF4 and VEGF/TF4 ratio are independant prognostic parameters in lung cancer. Key words: Nonsmall cell lung cancer, angiogenesis, VEGF, TF4.
Açıklama
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Tıpta Uzmanlık
Tıpta Uzmanlık
Anahtar Kelimeler
Göğüs Hastalıkları, Chest Diseases ; Onkoloji
