Blood Levels of GDF15 and Osteopontin May Help Tell Uterine Sarcoma From Benign Fibroids
Two blood proteins, GDF15 and osteopontin, separated aggressive uterine sarcoma from benign leiomyoma, and GDF15 independently predicted shorter progression-free survival.
Résumé
Uterine sarcoma is rare and aggressive, and it is hard to tell from common benign fibroids (leiomyomas) before surgery. Japanese researchers measured three blood proteins, GDF15, progranulin and osteopontin (OPN), in 38 women with uterine sarcoma and 67 with leiomyoma. GDF15 and OPN were significantly higher in sarcoma, and both separated the two conditions well (AUC about 0.88). The established markers CA125 and LDH did not separate them. GDF15 also predicted worse progression-free survival and remained an independent predictor after adjustment for CA125, LDH and FIGO stage (HR 3.01). The finding held when carcinosarcomas were excluded. The study is small and retrospective, so these results need validation in larger prospective cohorts before routine clinical use.
Résumé détaillé
Uterine sarcomas make up only 1–2% of malignant uterine tumors, but they behave aggressively and carry a poor prognosis. Benign leiomyomas (fibroids) are extremely common, and imaging and routine blood tests such as CA125 and LDH cannot reliably distinguish the two before surgery. A simple blood test that flags sarcoma risk and predicts outcome would be a real clinical advance.
Researchers at the University of Fukui and the National Cancer Center Hospital in Japan studied 38 women with uterine sarcoma (24 carcinosarcoma, 7 leiomyosarcoma, 4 undifferentiated sarcoma, 3 low-grade endometrial stromal sarcoma) and 67 women with leiomyoma, all treated in 2015–2019. The leiomyoma patients had been suspected of sarcoma on imaging. Pre-treatment serum was analyzed by ELISA for GDF15, progranulin (PGN) and OPN. Tumor tissue was scored by immunohistochemistry. The candidate proteins had been chosen earlier from public gene-expression databases. Analyses included ROC and precision-recall curves, Kaplan–Meier survival, and Cox regression, with a separate analysis excluding carcinosarcoma.
Mean serum GDF15 was 1.42 ng/mL in sarcoma versus 0.44 in leiomyoma, and mean OPN was 22.04 versus 7.58 ng/mL (both p < 0.001). GDF15 discriminated sarcoma from leiomyoma with an AUC of 0.883 at a cutoff of 0.45 ng/mL, and OPN with an AUC of 0.881 at 10.61 ng/mL. AUPRC values were 0.888 and 0.870. LDH, CA125 and PGN did not discriminate overall. Tumor tissue staining for GDF15, PGN and OPN was much higher in sarcoma, and tissue scores correlated with serum levels for GDF15 and OPN.
For prognosis, high GDF15 (≥2.22 ng/mL) was linked to markedly worse progression-free survival (univariate HR 6.48, p < 0.001). In a multivariate model with FIGO stage, LDH and CA125, GDF15 was the only independent predictor of progression-free survival (HR 3.01, 95% CI 1.04–8.67, p = 0.042). It remained independent when carcinosarcomas were excluded, although the confidence interval was very wide (HR 32.92, 1.08–1004). For overall survival, LDH was the independent predictor in the full cohort, and none was independent after excluding carcinosarcoma.
The results suggest GDF15 and OPN could support preoperative risk stratification and GDF15 could inform prognosis. Important caveats apply: the cohort is small and retrospective, the benign and malignant groups differ markedly in age, cutoffs were derived from the same data they were tested on, and the subgroup without carcinosarcoma had only 14 patients. External prospective validation is needed.
Principales conclusions
- Serum GDF15 was about 3-fold higher in uterine sarcoma than in leiomyoma (1.42 vs 0.44 ng/mL, p < 0.001).
- GDF15 and OPN each discriminated sarcoma from leiomyoma with an AUC of about 0.88; CA125, LDH and PGN did not.
- High GDF15 predicted worse progression-free survival and was independent of CA125, LDH and FIGO stage (HR 3.01, p = 0.042).
- GDF15 remained an independent PFS predictor after excluding carcinosarcoma, though with a very wide confidence interval (HR 32.92).
- Tumor tissue staining for GDF15 and OPN was higher in sarcoma and correlated with serum levels.
Méthodologie
Retrospective two-center study of 38 uterine sarcoma and 67 leiomyoma patients treated in 2015–2019. Pre-treatment serum GDF15, progranulin and OPN were measured by ELISA and tissue expression by immunohistochemistry. Diagnostic performance used ROC and precision-recall curves, and prognosis used Kaplan–Meier and Cox regression, with a sensitivity analysis excluding carcinosarcoma.
Limites de l'étude
The sample is small and retrospective, with few non-carcinosarcoma cases (n = 14) and very wide confidence intervals in that subgroup. Sarcoma patients were much older than leiomyoma patients (mean 62 vs 45 years), which may confound marker differences, and cutoffs were optimized in the same data without independent validation. Treatment varied and the cohort was from Japan only, which may limit generalizability.
Ce résumé vous a plu ?
Recevez les dernières recherches sur la longévité dans votre boîte de réception chaque semaine.
Saisissez votre e-mail pour vous abonner :