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基于YAP的列线图预测肝细胞癌根治性切除术后患者的预后不良。

YAP-based nomogram predicts poor prognosis in patients with hepatocellular carcinoma after curative surgery.

作者信息

Zhou Wenxuan, Ye Feiyang, Yang Gaowei, Liu Chenghu, Pan Zeya, Zhang Chengjing, Liu Hui

机构信息

The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital (Second Military Medical University), Naval Medical University, Shanghai, China.

Department of Nutrition, Eastern Hepatobiliary Surgery Hospital (Second Military Medical University), Naval Medical University, Shanghai, China.

出版信息

J Gastrointest Oncol. 2024 Aug 31;15(4):1712-1722. doi: 10.21037/jgo-24-36. Epub 2024 Aug 5.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) ranks prominently in cancer-related mortality globally. Surgery remains the main therapeutic option for the treatment of HCC, but high post-operative recurrence rate makes prognostic prediction challenging. The quest for a reliable model to predict HCC recurrence continues to enhance prognosis. We aim to develop a nomogram with multiple factors to accurately estimate the risk of post-operative recurrence in patients with HCC.

METHODS

A single-center retrospective study on 262 patients who underwent partial hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital from May 2010 to April 2013 was conducted where immunohistochemistry assessed Yes-associated protein (YAP) expression in HCC. In the training cohort, a nomogram that incorporated YAP expression and clinicopathological features was constructed to predict 2-, 3-, and 5-year recurrence-free survival (RFS). The performance of the nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation.

RESULTS

A total of 262 patients who underwent partial hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital were included in our study. HCC patients with high YAP expression exhibited significantly higher recurrence and reduced overall survival (OS) rates compared to those with low YAP expression (P<0.001). YAP was significantly associated with alpha-fetoprotein (AFP) (P=0.03), microvascular invasion (MVI) (P<0.001), and tumor differentiation grade (P<0.001). In the training cohort, factors like YAP expression, hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA), Child-Pugh stage, tumor size, MVI, and tumor differentiation were identified as key elements for the predictive model. Two YAP-centric Nomograms were developed, with one focused on predicting postoperative OS and the other on RFS. The calibration curve further confirmed the model's accuracy in the training cohort. The validation cohort confirmed the model's predictive accuracy.

CONCLUSIONS

The proposed nomogram combining the YAP, a predictor of HCC progression, and clinical features achieved more-accurate prognostic prediction for patients with HCC after partial hepatectomy, which may help clinicians implement more appropriate interventions.

摘要

背景

肝细胞癌(HCC)在全球癌症相关死亡率中占显著地位。手术仍然是治疗HCC的主要治疗选择,但术后高复发率使得预后预测具有挑战性。寻求一种可靠的模型来预测HCC复发持续改善预后。我们旨在开发一种包含多个因素的列线图,以准确估计HCC患者术后复发风险。

方法

对2010年5月至2013年4月在东方肝胆外科医院接受HCC部分肝切除术的262例患者进行单中心回顾性研究,其中免疫组织化学评估HCC中Yes相关蛋白(YAP)的表达。在训练队列中,构建了一个纳入YAP表达和临床病理特征的列线图,以预测2年、3年和5年无复发生存期(RFS)。通过区分校准评估列线图的性能,并通过外部验证评估其临床实用性。

结果

我们的研究纳入了在东方肝胆外科医院接受HCC部分肝切除术的262例患者。与低YAP表达的HCC患者相比,高YAP表达的HCC患者表现出显著更高的复发率和更低的总生存率(OS)(P<0.001)。YAP与甲胎蛋白(AFP)(P=0.03)、微血管侵犯(MVI)(P<0.001)和肿瘤分化程度(P<0.001)显著相关。在训练队列中,YAP表达、乙肝表面抗原(HBsAg)、乙肝病毒脱氧核糖核酸(HBV-DNA)、Child-Pugh分期、肿瘤大小、MVI和肿瘤分化等因素被确定为预测模型的关键要素。开发了两个以YAP为中心的列线图,一个侧重于预测术后OS,另一个侧重于RFS。校准曲线进一步证实了模型在训练队列中的准确性。验证队列证实了模型的预测准确性。

结论

所提出的结合HCC进展预测因子YAP和临床特征的列线图,对部分肝切除术后的HCC患者实现了更准确的预后预测,这可能有助于临床医生实施更合适的干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c952/11399831/5456386ea546/jgo-15-04-1712-f1.jpg

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