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

Content Provider	Springer Nature : BioMed Central
Author	Sui, Qihai Hu, Zhengyang Jin, Xing Bian, Yunyi Liang, Jiaqi Zhang, Huan Yang, Huiqiang Lin, Zongwu Wang, Qun Zhan, Cheng Chen, Zhencong
Abstract	Background Neoadjuvant 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. Methods Single-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. Results 485 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. Conclusions NCS scores and related predictive models for CDDP-NACT were developed and validated to assist in selecting patients who might benefit from it.
Related Links	https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-023-01061-z.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	20453701
DOI	10.1186/s13578-023-01061-z
Journal	Cell & Bioscience
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2023-06-08
Access Restriction	Open
Subject Keyword	Cell Biology Microbiology Stem Cells Neurobiology Proteomics Neoadjuvant chemotherapy (NACT) Cisplatin (CDDP) Single-cell analysis Gene expression Drug resistance
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7/2023

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

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