Respiratory research · 2026
Activating KRAS mutations mark premalignant cystic structures in congenital pulmonary airway malformations.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
van Horik Cathy, Benthem Floor, Buscop-van Kempen Marjon, Boerema-de Munck Anne, van IJcken Wilfred F J, Wijnen Rene M H, Schnater Marco, Rottier Robbert J
Аннотация
BACKGROUND: Congenital Pulmonary Airway malformations (CPAM) may lead to malignant degeneration, and therefore many surgeons opt to resect CPAM even in asymptomatic patients. Previously, we identified Kirsten rat sarcoma virus (KRAS) mutations in a subset of CPAM patients, possibly indicating a pre-malignant state. In order to unify treatment strategy in (asymptomatic) patients we focused on KRAS mutations as a potential risk factor for developing malignancy in CPAM.
METHODS: Resected lung tissue of CPAM patients was separated in affected region ("cyst") and non-affected region ("control") to subsequently initiate airway organoids. Cyst and control organoids from the same patients with and without KRAS mutations (KRASPOS vs. KRASNEG) (n = 3) where processed for single cell RNA sequencing (scRNA-Seq), and the cellular composition of the organoids was validated by immunofluorescent staining. The role of KRAS was identified by manipulating the expression in the organoids.
RESULTS: ScRNA-Seq data revealed differences in cell proportions between KRASPOS and KRASNEG cyst, and control organoids. The significant differentially expressed genes in the KRASPOS cyst are comparable to those identified in lung cancer patients with KRAS mutations. Manipulation of KRAS expression showed that KRASPOS cyst organoids grew larger due to more proliferative cells and that KRAS directly affected the cell cycle.
CONCLUSIONS: KRASPOS cyst organoids show transcriptomic similarities with KRAS mutated lung cancers, show changes in cellular composition and have increased growth and proliferation. These findings support the hypothesis that KRAS mutated CPAM cysts belong to a group of CPAM patients at higher risk of developing a malignancy.
METHODS: Resected lung tissue of CPAM patients was separated in affected region ("cyst") and non-affected region ("control") to subsequently initiate airway organoids. Cyst and control organoids from the same patients with and without KRAS mutations (KRASPOS vs. KRASNEG) (n = 3) where processed for single cell RNA sequencing (scRNA-Seq), and the cellular composition of the organoids was validated by immunofluorescent staining. The role of KRAS was identified by manipulating the expression in the organoids.
RESULTS: ScRNA-Seq data revealed differences in cell proportions between KRASPOS and KRASNEG cyst, and control organoids. The significant differentially expressed genes in the KRASPOS cyst are comparable to those identified in lung cancer patients with KRAS mutations. Manipulation of KRAS expression showed that KRASPOS cyst organoids grew larger due to more proliferative cells and that KRAS directly affected the cell cycle.
CONCLUSIONS: KRASPOS cyst organoids show transcriptomic similarities with KRAS mutated lung cancers, show changes in cellular composition and have increased growth and proliferation. These findings support the hypothesis that KRAS mutated CPAM cysts belong to a group of CPAM patients at higher risk of developing a malignancy.