Аннотация
Частота рецидивов при раке яичников, шестого по распространенности вида рака среди женщин в мире, после положитель-
ного ответа на первую линию терапии достигает 85%. Отсутствие надежных средств прогнозирования индивидуального
риска возникновения метастазов и длительности безрецидивного периода существенно ограничивает возможности врача.
Цель исследования: оценка прогностической значимости показателей гранулоцитарного колониестимулирующего фактора
(G-CSF) и коллагеназы-3 в циркулирующих нейтрофилах при распространенном раке яичников.
Материал и методы. В ретроспективное исследование включены 72 пациентки с доброкачественными опухолями яичников
и с серозной high-grade аденокарциномой яичников до получения лечения. Контрольную группу составили 22 соматически
здоровые женщины. Методом иммуноферментного анализа в лизате нейтрофилов периферической крови определён уровень
G-CSF и матриксной металлопротеиназы (MMP-13), тканевого ингибитора матриксной металлопротеиназы (TIMP-1).
Статистическая обработка проведена с использованием Statistica 13.0 и Jamovi 2.4.14. Анализ времени без прогрессирования
(ВБП) пациентов проведён по методу регрессии Кокса и Каплана-Майера.
Результаты. Установлено значимое снижение уровня MMP-13 и повышение уровней G-CSF и TIMP-1 в циркулирующих ней-
трофилах у пациенток при раке яичников по сравнению с контролем. Анализ продолжительности безрецидивного периода
показал, что при Cut Point (G-CSF) 0,292 и ниже, медиана ВБП составляет 9,4 [3,1-18,2, 95% ДИ] месяцев, при Cut Point
MMP-13 в нейтрофилах 0,700 и выше медиана ВБП составляет 12 месяцев [8,1-27,7, 95% ДИ]. При дифференциальной
диагностике рака яичников и доброкачественных опухолей яичников вероятность возникновения рака составляет 86% при
повышении MMP13 в нейтрофилах (Sens.=0,89. Spec.=0,85).
Заключение. Уровни G-CSF и MMP-13 в циркулирующих нейтрофилах могут быть использованы в качестве прогностиче-
ских маркеров при оценке ВБП при распространенном раке яичников. Прогностической значимостью возникновения рециди-
ва обладают одновременно уровни MMР-13 и G-CSF в циркулирующих нейтрофилах пациенток с распространенным раком
яичников при наличии асцита.
Annotation
The recurrence rate for ovarian cancer, the sixth most common cancer among women worldwide, after a positive response to first-line
therapy is as high as 85%. The lack of reliable means of predicting the individual risk of metastases and the duration of the relapse-free
period significantly limits the doctor’s capabilities.
The aim of the study was to assess the prognostic significance of granulocyte colony-stimulating factor (G-CSF) and collagenase-3
levels in circulating neutrophils in advanced ovarian cancer.
Material and methods. The retrospective study included 72 patients with benign ovarian tumors and serous high-grade ovarian
adenocarcinoma before treatment. The control group consisted of 22 somatically healthy women. Using an enzyme immunoassay,
the levels of G-CSF and matrix metalloproteinase (MMP-13), tissue inhibitor of matrix metalloproteinase (TIMP-1) were determined
in peripheral blood neutrophil lysate. Statistical processing was carried out using Statistica 13.0 and Jamovi 2.4.14. Patients’
progression-free time (PFT) was analyzed using Cox and Kaplan-Meier regression.
Results. A significant decrease in the level of MMP-13 and an increase in the levels of G-CSF and TIMP-1 in circulating neutrophils
in patients with ovarian cancer compared to controls was established. Analysis of the duration of the relapse-free period showed that
with a Cut Point (G-CSF) of 0.292 and below, the median PFT is 9.4 [3.1 — 18.2, 95% CI] months, and with a Cut Point MMP-13 in
neutrophils of 0.700 and above, the median PFT is 12 months [8.1 — 27.7, 95% CI]. In the differential diagnosis of ovarian cancer and
benign ovarian tumors, the probability of cancer is 86% with an increase in MMP13 in neutrophils (Sens.=0.89. Spec.=0.85).
Conclusion. Levels of G-CSF and MMP-13 in circulating neutrophils can be used as prognostic markers in assessing PFT in advanced
ovarian cancer. The levels of MMP-13 and G-CSF in circulating neutrophils of patients with advanced ovarian cancer in the presence
of ascites simultaneously have prognostic significance for the occurrence of relapse.
Key words: ovarian cancer; ascites; benign ovarian tumors; neutrophils; G-CSF; MMP-13; progression-free time
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