The genomic signature of resistance to platinum-containing neoadjuvant therapy based on single-cell data

Cell & Bioscience

Research

Qun Wang¹  Qihai Sui¹  Xing Jin¹  Cheng Zhan¹  Huan Zhang¹  Huiqiang Yang¹  Zhencong Chen¹  Zhengyang Hu¹  Yunyi Bian¹  Jiaqi Liang¹  Zongwu Lin¹ 

[1] Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, 200032, Shanghai, China;

关键词: Neoadjuvant chemotherapy (NACT);    Cisplatin (CDDP);    Single-cell analysis;    Gene expression;    Drug resistance;   

DOI  :  10.1186/s13578-023-01061-z

 received in 2023-03-13, accepted in 2023-05-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNeoadjuvant chemotherapy (NACT) becomes the first-line option for advanced tumors, while patients who are not sensitive to it may not benefit. Therefore, it is important to screen patients suitable for NACT.MethodsSingle-cell data of lung adenocarcinoma (LUAD) and esophageal squamous carcinoma (ESCC) before and after cisplatin-containing (CDDP) NACT and cisplatin IC50 data of tumor cell lines were analyzed to establish a CDDP neoadjuvant chemotherapy score (NCS). Differential analysis, GO, KEGG, GSVA and logistic regression models were performed by R. Survival analysis were applied to public databases. siRNA knockdown in A549, PC9, TE1 cell lines, qRT-PCR, western-blot, cck8 and EdU experiments were used for further verification in vitro.Results485 genes were expressed differentially in tumor cells before and after neoadjuvant treatment for LUAD and ESCC. After combining the CDDP-associated genes, 12 genes, CAV2, PHLDA1, DUSP23, VDAC3, DSG2, SPINT2, SPATS2L, IGFBP3, CD9, ALCAM, PRSS23, PERP, were obtained and formed the NCS score. The higher the score, the more sensitive the patients were to CDDP-NACT. The NCS divided LUAD and ESCC into two groups. Based on differentially expressed genes, a model was constructed to predict the high and low NCS. CAV2, PHLDA1, ALCAM, CD9, IGBP3 and VDAC3 were significantly associated with prognosis. Finally, we demonstrated that the knockdown of CAV2, PHLDA1 and VDAC3 in A549, PC9 and TE1 significantly increased the sensitivity to cisplatin.ConclusionsNCS scores and related predictive models for CDDP-NACT were developed and validated to assist in selecting patients who might benefit from it.

【 授权许可】

CC BY   
© The Author(s) 2023

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