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Prediction of lymphovascular space invasion in endometrial cancer using the 55-gene signature selected by DNA microarray analysis


Autoři: Takafumi Watanabe aff001;  Reiko Honma aff002;  Manabu Kojima aff001;  Shinji Nomura aff001;  Shigenori Furukawa aff001;  Shu Soeda aff001;  Shinya Watanabe aff003;  Keiya Fujimori aff001
Působiště autorů: Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Fukushima, Japan aff001;  Nippon Gene Co., Ltd., Chiyoda, Tokyo, Japan aff002;  Medical-Industrial Translational Research Center, Fukushima Medical University School of Medicine, Fukushima, Japan aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223178

Souhrn

Lymphovascular space invasion (LVSI) is considered to be the beginning of lymphogenous and hematogenous metastases. It is strongly related to dissemination, and therefore could be a valuable predictive sign of lymph node metastases and distant spread. Recently, the presence of LVSI in endometrial cancer (EC) has been shown to be an independent prognostic factor. The preoperative diagnosis of LVSI by pathological examination is difficult and LVSI is detected after surgery. The aim of the current study was to explore candidate genes as potential diagnostic biomarkers and determine whether they are predictors of LVSI in patients with EC. A total of 88 surgical specimens obtained from EC patients who had undergone surgical resection at Fukushima Medical University Hospital between 2010 and 2015 were analyzed using DNA microarray. LVSI was significantly associated with poor prognostic factors in EC such as higher tumor grade, lymph node metastasis, deep myometrium invasion, advanced stage and recurrence. Fifty-five candidate genes were significantly differentially expressed between 26 LVSI-positive and 62 LVSI-negative samples. All 88 samples were divided into two groups according to hierarchical clustering of 55 genes. Regarding diagnostic accuracy, sensitivity and negative predictive value were both high (92% and 95%, respectively); further, specificity and positive predictive value were both moderate (63% and 71%, respectively). Our data suggests that the 55-gene signature could contribute to predicting LVSI in EC, and provide clinically important information for better management. The molecular signatures of 55 genes may be also useful for understanding the underlying mechanism of LVSI.

Klíčová slova:

Diagnostic medicine – Gene expression – Histology – Lymph nodes – Metastasis – Microarrays – Surgical and invasive medical procedures – Hierarchical clustering


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