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Dataset: GSE175716 |
Dataset summary for GSE175716 |
Datast information | Dataset | GSE175716 |
PMID | 34421602 | |
Raw data ID/link | PRJNA733283 | |
Organism | Homo sapiens | |
Source | PDX | |
Tissue | Tumor tissue | |
Cancer type level1 | Liver cancer | |
Cancer type level2 | Advanced hepatocellular carcinoma | |
Regimen | sorafenib | |
Drug type | Targeted therapy | |
Sample size | resistant 1, sensitive 2 | |
Cell number | 6823 | |
Extract protocol | BD Rhapsody system | |
Data processing | NovelBio Bio-Pharm Technology Co., Ltd. | |
Public date | Public on Aug 24, 2021 | |
Description | This dataset has 3 PDX. |
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Drug summary for GSE175716 |
Drug name | DrugBank ID | Drug type | Targets name | Targets uniprot ID |
"Sorafenib" | DB00398 | small molecule | BRAF; RAF1; FLT4; KDR; FLT3; PDGFRB; KIT; FGFR1; RET; FLT1 | P15056; P04049; P35916; P35968; P36888; P09619; P10721; P11362; P07949; P17948 |
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Umap of single cell types and conditions (resistant and sensitive) |
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Umap of cell types![]() | Umap of conditions![]() |
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Comparison of cell composition between the resistant and sensitive groups |
![]() * represents significant difference. (If the image exists, the user can click on it to enlarge it in a new window.) |
![]() * represents significant difference. (If the image exists, the user can click on it to enlarge it in a new window.) |
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Comparison of ITH and EMT scores of malignant cells between the resistant and sensitive groups |
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Comparison of ITH scores![]() | Comparison of EMT scores![]() |
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Difference of cell-cell interactions between the resistant and sensitive groups |
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Differentially expressed genes (DEGs) between the resistant and sensitive groups for each cell type |
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Gene symbol | Gene id | avg_log2FC | p_val | p_val_adj | pct.1 | pct.2 | Cell type | Timepoint |
S100A8 | ENSG00000143546 | 6.13304 | 0.00e+00 | 0.00e+00 | 0.98 | 0.073 | Malignant cells | NA |
CHI3L1 | ENSG00000133048 | 5.27994 | 0.00e+00 | 0.00e+00 | 0.999 | 0.293 | Malignant cells | NA |
S100A9 | ENSG00000163220 | 4.84885 | 0.00e+00 | 0.00e+00 | 0.996 | 0.39 | Malignant cells | NA |
VIM | ENSG00000026025 | 4.30409 | 0.00e+00 | 0.00e+00 | 0.995 | 0.173 | Malignant cells | NA |
AKR1B1 | ENSG00000085662 | 3.98751 | 0.00e+00 | 0.00e+00 | 0.923 | 0.103 | Malignant cells | NA |
PLIN2 | ENSG00000147872 | 3.31118 | 0.00e+00 | 0.00e+00 | 1 | 0.945 | Malignant cells | NA |
TF | ENSG00000091513 | 3.19404 | 0.00e+00 | 0.00e+00 | 0.947 | 0.482 | Malignant cells | NA |
ZNF117 | ENSG00000152926 | 2.82172 | 0.00e+00 | 0.00e+00 | 0.794 | 0.027 | Malignant cells | NA |
G0S2 | ENSG00000123689 | 2.79561 | 0.00e+00 | 0.00e+00 | 0.888 | 0.346 | Malignant cells | NA |
LDHB | ENSG00000111716 | 2.65773 | 0.00e+00 | 0.00e+00 | 0.833 | 0.015 | Malignant cells | NA |
S100A11 | ENSG00000163191 | 2.62682 | 0.00e+00 | 0.00e+00 | 0.951 | 0.306 | Malignant cells | NA |
SAA1 | ENSG00000288411 | 2.45164 | 0.00e+00 | 0.00e+00 | 0.581 | 0.101 | Malignant cells | NA |
MTND1P23 | ENSG00000225972 | 2.41209 | 0.00e+00 | 0.00e+00 | 0.775 | 0.227 | Malignant cells | NA |
RPL34P27 | ENSG00000232858 | 2.38189 | 0.00e+00 | 0.00e+00 | 0.958 | 0.424 | Malignant cells | NA |
PTX3 | ENSG00000163661 | 2.3419 | 0.00e+00 | 0.00e+00 | 0.641 | 0.053 | Malignant cells | NA |
PEG10 | ENSG00000242265 | 2.22297 | 0.00e+00 | 0.00e+00 | 0.878 | 0.313 | Malignant cells | NA |
APMAP | ENSG00000101474 | 2.10977 | 0.00e+00 | 0.00e+00 | 0.913 | 0.46 | Malignant cells | NA |
BRI3 | ENSG00000164713 | 2.06336 | 0.00e+00 | 0.00e+00 | 0.968 | 0.519 | Malignant cells | NA |
RPL34P26 | ENSG00000223676 | 2.05293 | 0.00e+00 | 0.00e+00 | 0.73 | 0.137 | Malignant cells | NA |
MARC1 | NA | 2.03441 | 0.00e+00 | 0.00e+00 | 0.749 | 0.27 | Malignant cells | NA |
PSAT1 | ENSG00000135069 | 1.99277 | 0.00e+00 | 0.00e+00 | 0.672 | 0.086 | Malignant cells | NA |
SRI | ENSG00000075142 | 1.92846 | 0.00e+00 | 0.00e+00 | 0.989 | 0.72 | Malignant cells | NA |
AKR1C2 | ENSG00000151632 | 1.91963 | 0.00e+00 | 0.00e+00 | 1 | 0.952 | Malignant cells | NA |
CMAS | ENSG00000111726 | 1.84763 | 0.00e+00 | 0.00e+00 | 0.736 | 0.317 | Malignant cells | NA |
EFNA1 | ENSG00000169242 | 1.8422 | 0.00e+00 | 0.00e+00 | 0.871 | 0.428 | Malignant cells | NA |
PI3 | ENSG00000124102 | 1.83254 | 0.00e+00 | 0.00e+00 | 0.598 | 0.252 | Malignant cells | NA |
CPVL | ENSG00000106066 | 1.81079 | 0.00e+00 | 0.00e+00 | 0.671 | 0 | Malignant cells | NA |
VGLL2 | ENSG00000170162 | 1.78333 | 0.00e+00 | 0.00e+00 | 0.544 | 0.001 | Malignant cells | NA |
MT-TP | ENSG00000210196 | 1.78161 | 0.00e+00 | 0.00e+00 | 0.696 | 0.308 | Malignant cells | NA |
WDR86-AS1 | ENSG00000243836 | 1.76991 | 0.00e+00 | 0.00e+00 | 0.602 | 0.002 | Malignant cells | NA |
TRIB1 | ENSG00000173334 | 1.74245 | 0.00e+00 | 0.00e+00 | 0.995 | 0.673 | Malignant cells | NA |
FOXQ1 | ENSG00000164379 | 1.74188 | 0.00e+00 | 0.00e+00 | 0.69 | 0.236 | Malignant cells | NA |
AC010343.1 | NA | 1.69984 | 0.00e+00 | 0.00e+00 | 0.961 | 0.602 | Malignant cells | NA |
AP001324.1 | NA | 1.69084 | 0.00e+00 | 0.00e+00 | 1 | 0.887 | Malignant cells | NA |
RPS18 | ENSG00000223367 | 1.66159 | 0.00e+00 | 0.00e+00 | 1 | 0.906 | Malignant cells | NA |
EEF1A1 | ENSG00000156508 | 1.66159 | 0.00e+00 | 0.00e+00 | 1 | 0.999 | Malignant cells | NA |
AL138826.1 | NA | 1.65275 | 0.00e+00 | 0.00e+00 | 0.578 | 0.159 | Malignant cells | NA |
RPS10 | ENSG00000124614 | 1.64616 | 0.00e+00 | 0.00e+00 | 0.961 | 0.541 | Malignant cells | NA |
GNAS | ENSG00000087460 | 1.61069 | 0.00e+00 | 0.00e+00 | 1 | 0.921 | Malignant cells | NA |
CD36 | ENSG00000135218 | 1.60391 | 0.00e+00 | 0.00e+00 | 0.872 | 0.494 | Malignant cells | NA |
RPL39 | ENSG00000198918 | 1.55092 | 0.00e+00 | 0.00e+00 | 0.998 | 0.937 | Malignant cells | NA |
CSTB | ENSG00000160213 | 1.54995 | 0.00e+00 | 0.00e+00 | 0.997 | 0.957 | Malignant cells | NA |
CKB | ENSG00000166165 | 1.5378 | 0.00e+00 | 0.00e+00 | 0.653 | 0.184 | Malignant cells | NA |
ECHDC1 | ENSG00000093144 | 1.5191 | 0.00e+00 | 0.00e+00 | 0.898 | 0.523 | Malignant cells | NA |
IRS2 | ENSG00000185950 | 1.46589 | 0.00e+00 | 0.00e+00 | 0.923 | 0.57 | Malignant cells | NA |
DUSP9 | ENSG00000130829 | 1.46244 | 0.00e+00 | 0.00e+00 | 0.553 | 0 | Malignant cells | NA |
MT-CO3 | ENSG00000198938 | 1.4533 | 0.00e+00 | 0.00e+00 | 1 | 1 | Malignant cells | NA |
RPS3A | ENSG00000145425 | 1.43977 | 0.00e+00 | 0.00e+00 | 0.997 | 0.767 | Malignant cells | NA |
RPL37P2 | ENSG00000239559 | 1.43714 | 0.00e+00 | 0.00e+00 | 0.983 | 0.783 | Malignant cells | NA |
MARCKS | ENSG00000277443 | 1.43712 | 0.00e+00 | 0.00e+00 | 0.985 | 0.759 | Malignant cells | NA |
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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples |
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Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples |
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Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines |
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Enrichment results for 5 known drug resistance mechanisms in malignant cells |
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Mechnism | Pval | FDR | Signature | Geneset | Overlap | Background | Cell type | Enriched Genes |
Unusual Activation of Pro-survival Pathway | 9.20e-29 | 4.60e-28 | 2874 | 781 | 208 | 23467 | Malignant cells | PPP2R5A,ADAM10,ADAM9,AKT2,ANXA2,AREG,CDH1,CDK6,CDKN1A,CUL5,DUSP6,GLS,HIF1A,HMGB1,HMOX1,HSPA1A,EIF4G1,IFI27,JUN,PKM,MAGEA6,MAGEA12,MCL1,MEF2D,MET,MAPK1,MUC1,MYC,NFKB1,PARP1,RAB6A,KRAS,RPS6,SELENOW,SMAD4,SOX4,SOX9,SRC,STMN1,TGFBR2,TPD52,TYMS,VOPP1,XIAP,YAP1,YWHAZ,SLC25A5,AGR2,AKAP12,AKT3,ANXA1,NET1,BAK1,BCL10,BID,BRD4,BTG1,CAV2,CCL2,ALCAM,CDC27,CDKN2A,CLU,CTNND1,CXCR4,DDR1,DICER1,DKK1,DUSP1,E2F6,EGR1,EGR2,EHF,HSP90B1,EP300,EPHA2,ERCC1,EREG,ETS1,EZH2,EZR,FAT1,FGF2,FN1,FIS1,FOXA1,FTL,FUS,GAPDH,GATA6,GRB2,GCLM,GSR,HBEGF,HIPK3,HMGB2,HSPA8,HSPB1,IDH1,NFKBIA,CXCL8,JAG1,AK4,KAT6A,RPS6KA3,RPS6KB1,LAMP2,LASP1,LATS2,LDHA,MAP3K1,MAP3K5,MAP3K8,MAGEA3,MDM2,MED1,MITF,MAPK3,MOB1A,MAP2K2,IGF2R,MSH2,NF1,NQO1,NUCKS1,OAZ2,SPP1,PDCD10,PDE4D,PTGS2,PGK1,PRKDC,PSMB5,PTPN12,RAC1,RAP1B,RASSF1,RAB22A,RICTOR,RRM1,HNRNPA1,RSF1,RSU1,S100A8,S100A11,SAV1,SDC2,SFPQ,SIAH2,SIRT1,SMAD3,SMC4,SOCS6,SRI,SP1,SPIN1,SRF,STAT5B,TPT1,TFAM,TGFBR1,TNFAIP3,TNFSF10,TOM1,TOP1,TWF1,USP14,WEE1,YBX1,YES1,ZEB1,ZNF217,ENO1,FASN,MAGEA4,RASS |
Aberration of the Drug's Therapeutic Target | 2.10e-01 | 5.20e-01 | 2874 | 90 | 14 | 23467 | Malignant cells | AKT2,CDK6,MET,CREBBP,CDKN2A,EZH2,IDH1,MAP2K2,PTGS2,JAK1,SF3B1,NPM1,AKR1B1,TOP2A |
Drug Inactivation by Structure Modification | 4.30e-01 | 6.00e-01 | 2874 | 27 | 4 | 23467 | Malignant cells | CES1,CDA,NME1,PON1 |
Irregularity in Drug Uptake and Drug Efflux | 4.80e-01 | 6.00e-01 | 2874 | 37 | 5 | 23467 | Malignant cells | SLC3A2,ABCB1,ABCC2,SLC4A4,SLC7A11 |
Epigenetic Alteration of DNA, RNA or Protein | 1.00e+00 | 1.00e+00 | 2874 | 455 | 27 | 23467 | Malignant cells | H2AFY,MET,TRIP6,TYMS,XIAP,CREBBP,CCL2,CDKN2A,CXCR4,EZH2,GAPDH,IDH1,CXCL8,MAP3K8,MAPK3,RASSF1,SIRT1,SMC4,TIMP1,SNHG14,GDI2,AKT3,PPP1R15A,SMYD2,MT-CO2,NABP1,HULC |
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Up-regulated Hallmark | Up-regulated KEGG | Up-regulated GO BP |
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Down-regulated Hallmark | Down-regulated KEGG | Down-regulated GO BP |
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MicroRNAs (miRNAs) regulating drug resistance-related DEGs for malignant cells |
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Regulating up-regulated DEGs in resistant group | Regulating down-regulated DEGs in resistant group |
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Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type |
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Motifs and TFs regulating up-regulated DEGs in resistant group |
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Motifs and TFs regulating down-regulated DEGs in resistant group |
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Differentially expressed genes act as transcription factors |
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TF | motif | Expression | Cell type | Timepoint |
ZNF704 | metacluster_144.3 | up | Malignant cells | NA |
JUND | metacluster_160.20 | up | Malignant cells | NA |
TRIM28 | transfac_pro__M01199 | up | Malignant cells | NA |
THAP1 | metacluster_141.5 | down | Malignant cells | NA |
SP1 | transfac_pro__M01219 | down | Malignant cells | NA |
E2F6 | metacluster_55.3 | down | Malignant cells | NA |
EGR1 | metacluster_55.3 | down | Malignant cells | NA |
CEBPD | taipale_tf_pairs__ETV5_CEBPD_NSCGGANNTTRCGYAAN_CAP | down | Malignant cells | NA |
GMEB1 | dbtfbs__GMEB1_K562_ENCSR928KOR_merged_N1 | down | Malignant cells | NA |
MAX | taipale_tf_pairs__TFAP2C_MAX_TNSCCNNNGGSNNNNCACGTGN_CAP_repr | down | Malignant cells | NA |
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1 | "Sun X, Zhang Y, Li H, Zhou Y, Shi S, Chen Z, He X, Zhang H, Li F, Yin J, Mou M, Wang Y, Qiu Y, Zhu F. DRESIS: the first comprehensive landscape of drug resistance information. Nucleic Acids Res. 2023 Jan 6;51(D1):D1263-D1275. doi: 10.1093/nar/gkac812. PMID: 36243960; PMCID: PMC9825618." |
2 | "Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037. PMID: 29126136; PMCID: PMC5753335." |