一项关于TIMP1作为胃癌和结肠癌预后生物标志物的前瞻性队列研究。

A prospective cohort study of TIMP1 as prognostic biomarker in gastric and colon cancer.

作者信息

Macedo Filipa Castro, Cunha Nuno, Pereira Tatiana Cunha, Soares Rita Felix, Monteiro Ana Raquel, Bonito Nuno, Valido Frederico, Sousa Gabriela

机构信息

Medical Oncology Department, Portuguese Oncology Institute of Coimbra, Coimbra, Portugal.

Medical Pathology Department, Portuguese Oncology Institute of Coimbra, Coimbra, Portugal.

出版信息

Chin Clin Oncol. 2022 Dec;11(6):43. doi: 10.21037/cco-22-69. Epub 2022 Nov 22.

DOI:10.21037/cco-22-69

PMID:36509552

Abstract

BACKGROUND

Tissue inhibitor metalloproteinase 1 (TIMP1) inhibits proteins which has proteolytic activity, but in cancer it contributes for tumoral invasion and metastization. The authors investigated the expression of TIMP1 in different digestive cancer types. The aim of this study was to test TIMP1 as a serum marker since in clinical practice there is a lack of biomarkers to monitor the response to treatments or to detect early relapses.

METHODS

It was performed a prospective study with recently diagnosed patients with gastrointestinal cancers. Patients with esophageal, gastric, colon, rectal, hepatocarcinoma, and cholangiocarcinoma at any stage, that did not perform any type of treatment, were included. Enzyme-linked immunosorbent assays and chemiluminescence were used to quantify levels of TIMP1. The differences of the Kaplan-Meier survival curves were tested for statistical significance with the log rank test, and the 95% confidence intervals were calculated. Multivariate analysis was done using the COX proportional hazard model and a forward stepwise method. Statistical analyses were done using the IBM SPSS Statistics version 26.0. P value inferior to 0.05 was considered significant.

RESULTS

A total of 190 patients were recruited: 54.7% males, median age of 68 years old, 57.9% with colorectal cancer followed by esophagogastric disease with 22.6%. TIMP1 level were increased in 29.5%. In colon cancer, patients with higher levels of TIMP1 are associated with worse progression free survival (PFS) (P=0.007) and overall survival (OS) (P=0.036). No relationship was seen with Rat sarcoma virus (RAS), B-raf (BRAF) and Microsatellite instability status (MSI). In gastric cancer, patients with higher levels of TIMP1 are associated with worse OS (P=0.020), with no difference in PFS.

CONCLUSIONS

Higher TIMP1 levels in gastric and colon cancer patients are associated with worse prognosis. Further studies are needed: higher number of patients and sequential measurements of TIMP1 during patient treatments.

摘要

背景

组织金属蛋白酶抑制剂1（TIMP1）可抑制具有蛋白水解活性的蛋白质，但在癌症中，它会促进肿瘤侵袭和转移。作者研究了TIMP1在不同类型消化系统癌症中的表达情况。本研究的目的是测试TIMP1作为一种血清标志物，因为在临床实践中，缺乏用于监测治疗反应或检测早期复发的生物标志物。

方法

对近期诊断为胃肠道癌症的患者进行了一项前瞻性研究。纳入了处于任何阶段、未接受任何类型治疗的食管癌、胃癌、结肠癌、直肠癌、肝癌和胆管癌患者。采用酶联免疫吸附测定和化学发光法来定量TIMP1水平。使用对数秩检验对Kaplan-Meier生存曲线的差异进行统计学显著性检验，并计算95%置信区间。使用COX比例风险模型和向前逐步法进行多变量分析。使用IBM SPSS Statistics 26.0版本进行统计分析。P值小于0.05被认为具有显著性。

结果

共招募了190名患者：男性占54.7%，中位年龄为68岁，57.9%为结直肠癌患者，其次是食管胃疾病患者，占22.6%。29.5%的患者TIMP1水平升高。在结肠癌中，TIMP1水平较高的患者无进展生存期（PFS）较差（P=0.007），总生存期（OS）也较差（P=0.036）。未发现与鼠肉瘤病毒（RAS）、B-raf（BRAF）和微卫星不稳定性状态（MSI）存在关联。在胃癌中，TIMP1水平较高的患者OS较差（P=0.020），PFS无差异。