A meta-analysis of predictive value of blood biomarkers in gestational trophoblastic neoplasia
Abstract
Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to play a diagnostic and predictive role in gestational trophoblastic disease. However, the conclusions are still ambiguous. This meta-analysis aimed to evaluate the combined predictive value of NLR and PLR in the malignant progression of gestational trophoblastic disease. Method: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and China Biomedical Literature Database were searched for the relevant literature published up to 1 October 2022. Study selection and data extraction were performed independently by two reviewers. All analyses were performed using Revman, MetaDisc and STATA software. Results: A total of 858 patients from five studies were included in this meta-analysis. The pooled sensitivity and specificity of NLR were 0.8 (95% CI: 0.71–0.88) and 0.73 (95% CI: 0.69–0.76), respectively, and the area under curve of the summary receiver operating curve was 0.81. The pooled sensitivity and specificity of PLR were 0.87 (95% CI: 0.75–0.95) and 0.49 (95% CI: 0.44–0.54), respectively, and the area under curve of the summary receiver operating curve was 0.88. I2 statistic and Deek's funnel plot showed no heterogeneity and publication bias. Conclusion: NLR can accurately predict the progression from hydatidiform mole to gestational trophoblastic neoplasia and is a promising biomarker in further follow-up.
Papers of special note have been highlighted as: • of interest
References
- 1. . Gestational trophoblastic disease. Lancet 376(9742), 717–729 (2010). • This study helps people to understand and confront gestational trophoblastic disease.
- 2. Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc. Netw. 17(11), 1374–1391 (2019).
- 3. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Systemat. Rev.
doi:10.1002/14651858.CD007289.pub3(9) , (2017). - 4. The impact of pulmonary metastases on therapeutic response and prognosis in malignant gestational trophoblastic neoplasia patients: a retrospective cohort study. Eur. J. Cancer 161, 119–127 (2022).
- 5. . Malignancy risk scoring of hydatidiform moles. Asian Pac. J. Cancer Prev. 16(6), 2441–2445 (2015).
- 6. Diagnosis and management of gestational trophoblastic disease: 2021 update. Int. J. Gynaecol. Obstet. 155(Suppl. 1), 86–93 (2021).
- 7. Doppler-based predictive model for methotrexate resistance in low-risk gestational trophoblastic neoplasia with myometrial invasion: prospective study of 147 patients. Ultrasound Obstet. Gynecol. 57(5), 829–839 (2021).
- 8. . Gestational trophoblastic neoplasia – pathogenesis and potential therapeutic targets. Lancet Oncol. 8(7), 642–650 (2007).
- 9. . PD-L1 expression in human placentas and gestational trophoblastic diseases. Int. J. Gynecol. Pathol. 36(2), 146–153 (2017).
- 10. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl Cancer Inst. 106(6), dju124 (2014).
- 11. . Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 19(1), 2 (2017).
- 12. Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) Predict clinical outcome in patients with stage IIB cervical cancer. J. Oncol. 2021, 2939162 (2021).
- 13. Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer. BMC Cancer 19(1), 672 (2019).
- 14. . Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or monocyte-to-lymphocyte ratio in endometrial neoplasms: a systematic review and meta-analysis. Front. Oncol. 12, 734948 (2022).
- 15. Predictive role of the neutrophil lymphocyte ratio for invasion with gestational trophoblastic disease. Asian Pac. J. Cancer Prev. 15(10), 4203–4206 (2014).
- 16. . Predictive role of the neutrophil-lymphocyte ratio for hydatidiform mole canceration. J. Pract. Obstet. Gynecol. 32(04), 294–297 (2016).
- 17. Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies. J. Matern.-Fetal Neonat. Med. 31(3), 271–277 (2017).
- 18. . Predictive value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, hunman chronic gonadotropin and maximum diameter of intrauterine mass for prognosis of hydatidiform moles. Guangxi Med. J. 41(22), 2875–2878 (2019).
- 19. . Predictive value of peripheral systemic inflammatory markers in the malignancy transformation of complete hydatidiform mole. J. Pract. Obstet. Gynecol. 36(01), 31–36 (2020).
- 20. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020). Am. J. Chin. Med. 48(6), 1279–1313 (2020).
- 21. Evaluation and suggestions for improving the FIGO 2000 staging criteria for gestational trophoblastic neoplasia: a ten-year review of 1420 patients. Gynecol. Oncol. 149(3), 539–544 (2018).
- 22. . FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int. J. Gynaecol. Obstet. 70(2), 209–262 (2000). • These are guidelines that doctors use to treat gynecologic cancers.
- 23. . Diagnostic value of neutrophil-lymphocyte ratio in preeclampsia: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 98(51), e18496 (2019).
- 24. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann. Intern. Med. 155(8), 529–536 (2011).
- 25. . Diagnostic and prognostic accuracy of Protein C in adult patients with sepsis: protocol for a systematic review and meta-analysis. BMJ Open 11(9), e050754 (2021).
- 26. . Measuring inconsistency in meta-analyses. BMJ 327(7414), 557–560 (2003).
- 27. NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation. J. Mol. Med. 97(3), 355–367 (2019).
- 28. . Maternal heterozygous NLRP7 variant results in recurrent reproductive failure and imprinting disturbances in the offspring. Eur. J. Hum. Genet. 25(8), 924–929 (2017).
- 29. . NLRP7 Is involved in the differentiation of the decidual macrophages. Int. J. Mol. Sci. 20(23), 5994 (2019).
- 30. . Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in discriminating precancerous pathologies from cervical cancer. J. Oncol. 2019, 2476082 (2019).
- 31. . The potential value of red blood cell distribution width in patients with invasive hydatidiform mole. J. Clin.Lab. Anal. 33(4), e22846 (2019).
- 32. Update on the diagnosis and management of gestational trophoblastic disease. Int. J. Gynaecol. Obstet. 143(Suppl. 2), 79–85 (2018).
- 33. NLRP7 promotes choriocarcinoma growth and progression through the establishment of an immunosuppressive microenvironment. Cancers 13(12), 2999 (2021). • This study describes a new mechanism of choriocarcinoma.
- 34. . The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines. Biochem. Biophys. Res. Comm. 434(3), 460–465 (2013).
- 35. Hematologic markers of distant metastases and poor prognosis in gynecological cancers. BMC Cancer 19(1), 141 (2019).
- 36. . A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br. J. Cancer 107(4), 695–699 (2012).
- 37. Pretreatment neutrophil-to-lymphocyte ratio predicts the benefit of gastric cancer patients with systemic therapy. Aging (Albany NY) 13(13), 17638–17654 (2021).
- 38. Pretreatment neutrophil-to-lymphocyte ratio (NLR) may predict the outcomes of advanced non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Front. Oncol. 10, 654 (2020).
- 39. . Establishing the prognostic value of platelet-to-lymphocyte ratio in cervical cancer: a systematic review and meta-analysis. Int. J. Gynecol. Cancer 29(4), 683–690 (2019).
- 40. . Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc. Natl Acad. Sci. USA 100(16), 9482–9487 (2003).
- 41. . Predicting prognosis and therapeutic response from interactions between lymphocytes and tumor cells. Mol. Oncol. 9(10), 2054–2062 (2015).
- 42. . Predictive value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Int. Immunopharmacol. 85, 106677 (2020).
- 43. . A meta-analysis of the platelet-lymphocyte ratio: a notable prognostic factor in renal cell carcinoma. Int. J. Biol. Markers 37(2), 123–133 (2022).
- 44. . Predicting malignant transformation of hydatidiform mole by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Chin. J. Reprod. Health 33(04), 342–346 (2022).