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PRAME和NY-ESO-1作为三阴性乳腺癌潜在治疗和预后生物标志物的作用。

The role of PRAME and NY-ESO-1 as potential therapeutic and prognostic biomarkers in triple-negative breast carcinomas.

作者信息

See Sharlene Helene C, Smith Steven H, Finkelman Brian S, LaBoy Carissa, Novo Jorge E, Siziopikou Kalliopi P, Blanco Luis Z

机构信息

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Pathol Res Pract. 2023 Jan;241:154299. doi: 10.1016/j.prp.2022.154299. Epub 2022 Dec 31.

Abstract

PRAME and NY-ESO-1 are cancer-testis antigens (CTAs) reported to be highly enriched in triple-negative breast cancers (TNBCs), against which vaccines and immunotherapies are currently being developed. This study aims to analyze PRAME and NY-ESO-1 expression in TNBCs and their correlation with clinical outcomes. This is a retrospective cohort study of TNBC patients who have undergone neoadjuvant chemotherapy. PRAME and NY-ESO-1 expression were assessed on pre-therapy biopsies as H-scores (percentage x intensity) with final H scores of 2-3 considered as positive. Association between expression and pathologic complete response (pCR), metastasis, and residual cancer burden (RCB) were assessed via logistic regression. Cox proportional hazards models were used to assess the association with progression-free survival. P-values < 0.05 were considered statistically significant. Sixty-three percent of 76 patients were positive for PRAME. In contrast, only 5 % were positive for NY-ESO-1. PRAME positivity was significantly associated with a lower likelihood of early metastatic disease (OR = 0.24, 95 % CI 0.08-0.62; P = 0.005). However, it was not significantly associated with pCR, RCB category, or progression-free survival. NY-ESO1 score was not significantly associated with early metastatic disease, pCR, RCB category, or progression-free survival. Our results suggest that PRAME positivity may be associated with a lower risk of early metastasis in TNBCs, but not with response to neoadjuvant chemotherapy or progression-free survival. The high expression of PRAME in TNBCs makes it a potential therapeutic target, while NY-ESO1 appears to be a less useful marker. However, further larger studies are needed to ascertain the utility of these markers.

摘要

PRAME和NY-ESO-1是癌症睾丸抗原(CTA),据报道在三阴性乳腺癌(TNBC)中高度富集,目前正在针对它们开发疫苗和免疫疗法。本研究旨在分析PRAME和NY-ESO-1在TNBC中的表达及其与临床结局的相关性。这是一项对接受新辅助化疗的TNBC患者的回顾性队列研究。在治疗前活检中评估PRAME和NY-ESO-1的表达,以H评分(百分比×强度)表示,最终H评分2 - 3被视为阳性。通过逻辑回归评估表达与病理完全缓解(pCR)、转移和残留癌负担(RCB)之间的关联。使用Cox比例风险模型评估与无进展生存期的关联。P值<0.05被认为具有统计学意义。76例患者中有63%的PRAME呈阳性。相比之下,只有5%的NY-ESO-1呈阳性。PRAME阳性与早期转移性疾病的可能性较低显著相关(OR = 0.24,95%CI 0.08 - 0.62;P = 0.005)。然而,它与pCR、RCB类别或无进展生存期没有显著关联。NY-ESO1评分与早期转移性疾病、pCR、RCB类别或无进展生存期没有显著关联。我们的结果表明,PRAME阳性可能与TNBC早期转移风险较低相关,但与新辅助化疗反应或无进展生存期无关。PRAME在TNBC中的高表达使其成为一个潜在的治疗靶点,而NY-ESO1似乎是一个不太有用的标志物。然而,需要进一步更大规模的研究来确定这些标志物的实用性。

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