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BIK 和 GRP78 蛋白表达可作为乳腺癌对术前化疗反应和生存的标志物。

BIK and GRP78 protein expression as possible markers of response to preoperative chemotherapy and survival in breast cancer.

机构信息

Medical Research Unit in Reproductive Medicine, Unidad Médica de Alta Especialidad Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", Instituto Mexicano Del Seguro Social, Río Magdalena 289, Colonia Tizapan San Ángel, Alcaldía Álvaro Obregón, CP 01090, Mexico City, Mexico.

Oncological Gynecology Service, Unidad Médica de Alta Especialidad Hospital de Gineco Obstetricia No. 3, "Dr. Víctor Manuel Espinosa de Los Reyes Sánchez", Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Calzada Vallejo, Esquina Antonio Valeriano, Colonia La Raza, Alcaldía Azcapotzalco, CP 02990, Mexico City, Mexico.

出版信息

Taiwan J Obstet Gynecol. 2021 Mar;60(2):245-252. doi: 10.1016/j.tjog.2021.01.003.

DOI:10.1016/j.tjog.2021.01.003

PMID:33678323

Abstract

OBJECTIVE

BIK and GRP78 have shown differential expression profiles in breast cancer (BC) tissue, in addition to its important participation in the pathophysiology of cancer. The purpose of this study was to evaluate the association of BIK and GRP78 protein expression with clinical and pathologic response to preoperative chemotherapy, recurrence, disease-free survival (DFS) and overall survival (OS), in patients with BC.

MATERIAL AND METHODS

Fifty-three patients who received preoperative chemotherapy where included in an observational, analytical and retrospective study to assess the BIK and GRP78 protein expression by immunohistochemistry in microarrays of BC tissue obtained before treatment. Associations between BIK and GRP78 expression with clinicopathological characteristics, clinical and pathologic response to preoperative chemotherapy, and recurrence were analyzed using Chi-square or Fisher's exact test. OS and postoperative DFS were assessed at 5-year follow-up by Kaplan-Meir curves, and the difference according to BIK and GRP78 expression was evaluated using the log-rank test. Bivariate analysis was performed using Cox risk proportion model. A p value < 0.05 was considered to be statistically significant.

RESULTS

BIK and GRP78 staining revealed positive expression in 37 (71.2%) and 35 patients (72.9%) respectively. Association between pathological complete response (pCR) and positive expression of BIK (p = 0.046), as well as between clinical complete response (cCR) and negative expression of GRP78 was observed (p = 0.048). Patients with expression of GRP78 had lower DFS (HR = 3.46; 95% CI 1.01-11.80; p = 0.047) and shorter OS (HR = 3.49; 95% CI 1.04 a 11.72; p = 0.043).

CONCLUSION

When finding association of GRP78 and BIK protein expression with the response (clinical and pathologic respectively) to preoperative chemotherapy, and GRP78 with DFS and OS, in patients with BC, our results suggest a potential prognostic value of both proteins; however, a larger sample size is required to confirm this.

摘要

目的

BIK 和 GRP78 在乳腺癌（BC）组织中表现出不同的表达谱，此外其还重要参与了癌症的病理生理学。本研究的目的是评估 BIK 和 GRP78 蛋白表达与 BC 患者术前化疗的临床和病理反应、复发、无病生存（DFS）和总生存（OS）之间的相关性。

材料和方法

53 名接受术前化疗的患者被纳入一项观察性、分析性和回顾性研究，以评估 BC 组织微阵列中通过免疫组织化学获得的 BIK 和 GRP78 蛋白表达。使用卡方或 Fisher 精确检验分析 BIK 和 GRP78 表达与临床病理特征、术前化疗的临床和病理反应以及复发之间的相关性。通过 Kaplan-Meier 曲线评估 5 年随访时的 OS 和术后 DFS，并使用对数秩检验评估根据 BIK 和 GRP78 表达的差异。使用 Cox 风险比例模型进行双变量分析。p 值<0.05 被认为具有统计学意义。

结果

BIK 和 GRP78 染色分别显示 37 例（71.2%）和 35 例患者（72.9%）呈阳性表达。观察到病理完全缓解（pCR）与 BIK 阳性表达之间的关联（p=0.046），以及临床完全缓解（cCR）与 GRP78 阴性表达之间的关联（p=0.048）。表达 GRP78 的患者 DFS 较低（HR=3.46；95%CI 1.01-11.80；p=0.047），OS 更短（HR=3.49；95%CI 1.04-11.72；p=0.043）。