DKK1 as a robust predictor for adjuvant platinum chemotherapy benefit in resectable pStage II-III gastric cancer

Zhiyuan Fan; Beiqin Yu; Tao Pan; Fangyuan Li; Jianfang Li; Junyi Hou; Wentao Liu; Liping Su; Zhenggang Zhu; Chao Yan; Bingya Liu

doi:10.1016/j.tranon.2022.101577

DKK1 as a robust predictor for adjuvant platinum chemotherapy benefit in resectable pStage II-III gastric cancer

Transl Oncol. 2023 Jan:27:101577. doi: 10.1016/j.tranon.2022.101577. Epub 2022 Nov 1.

Authors

Zhiyuan Fan¹, Beiqin Yu², Tao Pan², Fangyuan Li², Jianfang Li², Junyi Hou², Wentao Liu², Liping Su², Zhenggang Zhu², Chao Yan³, Bingya Liu⁴

Affiliations

¹ Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
² Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
³ Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: yanchaosuper@163.com.
⁴ Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: liubingya@sjtu.edu.cn.

Abstract

Background: Adjuvant chemotherapy (ACT) with 5-FU alone or 5-FU plus platinum after curative surgery improves the prognosis of pStage II-III gastric cancer (GC). However, only a subset of patients benefits from adjuvant platinum. To avoid the side effects of platinum, it is significant to accurately screen the patients who would benefit maximally with this treatment. The present study aimed to assess the value of DKK1 in predicting the benefit of adjuvant platinum chemotherapy in patients with pStage II -III GC.

Methods: Platinum sensitivity-related genes were screened by bioinformatics. DKK1 expression in 380 GC specimens was detected by immunohistochemistry (IHC) staining, and the correlation with adjuvant platinum-specific benefits were analyzed.

Results: DKK1 was screened as the most significant platinum sensitivity-related gene. In patients with DKK1^high GC, the estimated absolute 5-year overall survival (OS) benefits from adjuvant platinum for pStage II-III, II, IIIA, IIIB, and IIIC were 25.5%, 17.3%, 36.4%, 29.2% and 31.1%, respectively, and the estimated absolute 5-year disease-free survival (DFS) benefits in the corresponding stages were 27.4%, 17.5%, 36.7%, 29.7% and 31.5%, respectively. These benefits were significantly higher than those in the same TNM stage without adjusting for DKK1 status. The performance of DKK1 was independent of the TNM stage and other clinicopathological variables. Similar results were obtained in the TCGA and ACRG cohorts. Furthermore, nomograms were constructed to predict the survival benefits in DKK1 subgroups.

Conclusions: The stratification strategy based on DKK1 status is more precise than the TNM staging system for the selection of pStage II-III GC patients suitable for platinum-containing ACT.

Keywords: Adjuvant chemotherapy; DKK1; Gastric cancer; Platinum; Predictor.