Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma

ASRGL1 表达缺失是子宫内膜样子宫内膜癌疾病特异性生存的独立生物标志物

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作者:Per-Henrik D Edqvist, Jutta Huvila, Björn Forsström, Lauri Talve, Olli Carpén, Helga B Salvesen, Camilla Krakstad, Seija Grénman, Henrik Johannesson, Oscar Ljungqvist, Mathias Uhlén, Fredrik Pontén, Annika Auranen

Conclusions

Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.

Methods

Using The Human Protein Atlas (www.proteinatlas.org), the l-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n=229 and n=286) arranged as tissue microarrays. Staining

Objective

For endometrial carcinoma, prognostic stratification

Results

Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI=1.10-11.43; p=0.003) and 3.23 (95% CI=1.53-6.81; p=0.002) in the two cohorts, respectively. Of the 48 cases with Grade 3 Stage I tumor all disease-related deaths were associated with low ASRGL1 expression. Conclusions: Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended.

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