转化酸性卷曲螺旋蛋白 3：用于鉴别诊断和预测宫颈腺癌预后的新型标志物。

Transforming acidic coiled-coil protein-3: a novel marker for differential diagnosis and prognosis prediction in endocervical adenocarcinoma.

机构信息

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.

Department of Pathology, Sun Yat-Sen University Cancer Center, 651# Dong Feng Road East, Guangzhou, 510060, Guangdong, China.

出版信息

Mol Med. 2021 Jun 10;27(1):60. doi: 10.1186/s10020-021-00298-z.

DOI:10.1186/s10020-021-00298-z

PMID:34134633

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8210387/

Abstract

BACKGROUND

Endocervical adenocarcinoma (ECA) is further classified as human papillomavirus (HPV)-associated (HPVA) or non-HPVA (NHPVA), per the International Endocervical Adenocarcinoma Criteria and Classification (IECC). HPVA is a glandular tumor with stromal invasion and/or exophytic expansile-type invasion, associated with the typical molecular characteristics of high-risk HPV (HR-HPV) infection. Transforming acidic coiled-coil protein-3 (TACC3),an oncogene that is frequently abnormally expressed,represents a vital biomarker for multiple human malignancies. This study aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA.

METHODS

We analyzed 264 patients with ECA who underwent surgical resection, classifying their tumors into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6 and Ki-67 in tumors were evaluated by tissue microarray using immunohistochemistry (IHC). HPV subtypes were identified in formalin-fixed paraffin-embedded (FFPE) ECA tissues by the polymerase chain reaction (PCR).

RESULTS

ECA samples showed increased TACC3 expression relative to adjacent non-carcinoma samples. TACC3 expression was higher in HPVA than in NHPA. In the HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 levels were significantly related to tumor histological type (P = 0.006), nerve invasion (P = 0.003), differentiation (P = 0.004), surgical margin (P = 0.012), parametrium invasion (P = 0.040), P16 expression (P < 0.001), and Ki-67 (P = 0.004). Additionally, Kaplan-Meier analysis showed that TACC3 upregulation was associated with poor overall survival (OS, P = 0.001), disease-free survival (DFS, P < 0.001), and recurrence survival (P < 0.001). Multivariate analysis indicated that elevated TACC3 expression served as a marker to independently predict ECA prognosis. ROC curve analyses indicated that TACC3, P16, and HPV subtypes showed similar utility for distinguishing HPVA from NHPVA, with areas under the ROC curves of 0.640, 0.649, and 0.675, respectively. The combination of TACC3 and HPV subtypes improved the diagnostic performance of ECA compared with TACC3, P16, and HPV subtypes alone.

CONCLUSIONS

Taken together, our findings identify that TACC3 is a promising complementary biomarker for diagnosis and prognosis for patients with ECA.

摘要

背景

根据国际宫颈腺癌分类标准和分类（IECC），宫颈腺癌（ECA）进一步分为人乳头瘤病毒（HPV）相关（HPVA）或非 HPV 相关（NHPVA）。HPVA 是一种具有间质浸润和/或外生性扩张型浸润的腺体肿瘤，与高危型 HPV（HR-HPV）感染的典型分子特征相关。转化酸性卷曲螺旋蛋白 3（TACC3）是一种经常异常表达的致癌基因，是多种人类恶性肿瘤的重要生物标志物。本研究旨在探讨 TACC3 在 ECA 诊断和预后中的作用。

方法

我们分析了 264 例接受手术切除的 ECA 患者，将其肿瘤分为 HPVA 和 NHPVA 亚型。通过免疫组织化学（IHC）使用组织微阵列评估肿瘤中 TACC3、P16、MLH1、PMS2、MSH2、MSH6 和 Ki-67 的表达水平。通过聚合酶链反应（PCR）在福尔马林固定石蜡包埋（FFPE）的 ECA 组织中鉴定 HPV 亚型。

结果

ECA 样本与相邻非癌样本相比，TACC3 表达增加。HPVA 中 TACC3 的表达高于 NHPA。在 HPVA 亚型中，高 TACC3 表达与 P16 阳性、Ki-67 高表达显著相关。此外，TACC3 水平与肿瘤组织学类型（P=0.006）、神经侵犯（P=0.003）、分化（P=0.004）、手术切缘（P=0.012）、宫旁浸润（P=0.040）、P16 表达（P<0.001）和 Ki-67（P=0.004）显著相关。此外，Kaplan-Meier 分析表明，TACC3 上调与总生存（OS，P=0.001）、无病生存（DFS，P<0.001）和复发生存（P<0.001）不良相关。多变量分析表明，升高的 TACC3 表达可作为独立标志物预测 ECA 预后。ROC 曲线分析表明，TACC3、P16 和 HPV 亚型在区分 HPVA 和 NHPVA 方面具有相似的作用，ROC 曲线下面积分别为 0.640、0.649 和 0.675。与 TACC3、P16 和 HPV 亚型单独相比，TACC3 和 HPV 亚型的组合提高了 ECA 的诊断性能。