血管内皮生长因子、Ki-67 和蛋白 53 高表达是紫杉醇-卡铂新辅助化疗在 IB3、IIA2 和 IIB 期宫颈癌中疗效不佳的危险因素。

High Expression of Vascular Endothelial Growth Factor, Ki-67, and Protein 53 are Risk Factors for Poor Response of Paclitaxel-Carboplatin Neoadjuvant Chemotherapy in Stadium IB3, IIA2, and IIB Cervical Cancer.

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Udayana, Prof. Dr. I.G.N.G. Ngoerah, Denpasar, Bali, Indonesia.

出版信息

Asian Pac J Cancer Prev. 2024 Aug 1;25(8):2625-2631. doi: 10.31557/APJCP.2024.25.8.2625.

DOI:10.31557/APJCP.2024.25.8.2625

PMID:39205559

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11495431/

Abstract

BACKGROUND

The therapeutic strategy for stage IB3, IIA2, and IIB cervical cancer is still controversial. The modalities are chemoradiation, radical hysterectomy surgery, or administration of neoadjuvant chemotherapy followed by radical hysterectomy. Response to chemotherapy is determined by tumor vascularization or angiogenesis, proliferative activity, and genetic instability of cervical cancer. The marker of tumor cell proliferation is the Ki-67 protein. In cervical cancer, the p53 gene is suppressed by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 thereby inhibiting stabilization and activation of p53. This study aimed to prove that high expression of VEGF, Ki-67, and p53 are risk factors for a poor response to neoadjuvant chemotherapy.

METHODS

This was a case-control study that was conducted at the Department of Obstetrics and Gynecology in one tertiary hospital in Denpasar from October 2021 to April 2022. There were 56 samples included in this study, which were divided into two equal groups, namely good response and poor response to neoadjuvant chemotherapy. Data were analyzed using the software SPSS-24 including the Kolmogorov-Smirnov normality test, Chi-square, and multiple regression logistics. Data were presented in tables and described narratively.

RESULTS

It was found that the risk of a poor response to chemotherapy on the expression of VEGF VEGF, Ki-67, and p53 were 11.5, 15.0, and 8.33 times, respectively. We obtained a formula for calculating chemotherapy response, y = -7.3+ 1.6 VEGF + 1.6 Ki-67 + 1.8 p53. High VEGF, Ki-67, and p53 expressions were scored 1, and low expressions were scored 2. The limit value used is 0.05. The result y < 0.05 means the risk of poor response to chemotherapy and the value of y > 0.05 means good response.

CONCLUSION

This formulation can be used as a parameter to assess the risk of poor response to neoadjuvant chemotherapy in stage IB3, IIA2, and IIB cervical cancer which can be applied in clinical practice in the treatment of cervical cancer.

摘要

背景

IB3 期、IIA2 期和 IIB 期宫颈癌的治疗策略仍存在争议。治疗方式包括放化疗、根治性子宫切除术或新辅助化疗后行根治性子宫切除术。宫颈癌对化疗的反应取决于肿瘤血管生成或血管生成、增殖活性和遗传不稳定性。肿瘤细胞增殖的标志物是 Ki-67 蛋白。在宫颈癌中，p53 基因被人乳头瘤病毒（HPV）抑制。HPV E6 蛋白促进 p53 的降解，从而抑制 p53 的稳定和激活。本研究旨在证明 VEGF、Ki-67 和 p53 的高表达是对新辅助化疗反应不良的危险因素。

方法

这是一项病例对照研究，于 2021 年 10 月至 2022 年 4 月在登巴萨的一家三级医院的妇产科进行。本研究共纳入 56 例样本，分为对新辅助化疗反应良好和反应不良两组。数据分析采用 SPSS-24 软件进行，包括 Kolmogorov-Smirnov 正态性检验、卡方检验和多回归逻辑。数据以表格形式呈现，并以叙述性方式描述。

结果

发现 VEGF、Ki-67 和 p53 表达与化疗反应不良的风险分别为 11.5、15.0 和 8.33 倍。我们得出了一个计算化疗反应的公式，y = -7.3+1.6VEGF+1.6Ki-67+1.8p53。高 VEGF、Ki-67 和 p53 表达得分为 1，低表达得分为 2。使用的限值为 0.05。结果 y < 0.05 表示对化疗反应不良的风险，y > 0.05 表示反应良好。