SPK1/S1P axis confers gastrointestinal stromal tumors (GISTs) resistance of imatinib.

"the primers used for each snp were provided in supplementary data s1.; the specific information was supplied in the supplementary data s2.; this study included 29 gists patients who regularly took im orally and 11 gists patients who did not take im (supplementary data s3).; as shown in supplementary data s4 the difference between the highest and lowest im concentration was more than 12-fold as reflected in the huge individual differences of gists patients under im treatment.; the specific data between gender age and surgical operation and c min of im were shown in supplementary data s5-s7.; peaks were aligned and missing values were eliminated from the uhplc/ms data 2238 and 1020 metabolites in the esi + and esi - modes were screened through publicly available databases respectively which were demonstrated in supplementary data s8.; as depicted in supplementary data s9-s10 the differential metabolites in groups d to a b and c exhibited different distribution patterns which indicated the capacity to distinguish these metabolites in the groups treated or not with im.; as supplied in the supplementary data s11 the ic 50 value of gist-t1/imr cells was39 24 um while the value of gist-t1 cells was7 862 um.; the values in the dms pretreatment group were decreased dramatically when compared to im treatment only which supplied in the supplementary data s12."

"Declarations Conflict of interestThe authors declare that there are no conflicts of interest. Ethics approval and consent to participateAll participants provided informed consent to the protocol (Approval No. SCCHE-02–2020-044) was approved by the Review Ethic Board at the Sichuan Cancer Hospital. Consent for publicationNot applicable. Conflict of interest The authors declare that there are no conflicts of interest."

"The authors thank Prof. Wenbin Ou from Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, for kindly providing the valuable cell lines used in this study. This work was financially supported by the Outstanding Young Scientific Talent Foundation of Sichuan Province (No. 2022JDJQ0052); Science and Technology Program of Sichuan Province (No. 22NSFSC1458, No. 2022NSFSC0792, 2020YFS0417); Research Project of Sichuan Administration of Traditional Chinese Medicine (No. 2020JC0114); Beijing Xisike Clinical Oncology Research (No. Y-QL202101-0125); Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau (No. 2021-YF05-02064-SN, No. 2022-YF05-01591-SN)."