Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bioinformatic Analysis
2.2. Interactome Analyses
2.3. Pathway Enrichment Analyses
2.4. Patient Survival Analyses
2.5. Analyses of Transcriptional Variants
2.6. Decoding Drugs-CDH1 Mutation Gene Expression Signatures
2.7. Statistical Evaluations
3. Results
3.1. Gene Expression Signatures Associated to CDH1 Mutation in GC
3.2. Impact of Gene Mutations on CDH1 Transcription in GC
3.3. Gene Enrichment Analysis of Transcripts Positively Correlating with CDH1/Cadherin−1 Expression Levels in GC
3.4. Sonic Hedgehog (Shh) and Collagen-Linked Pathways, Cholesterol, and Humoral Metabolism Are Key Pathways in the Interactome of CDH1-Related Genes
3.5. Gain of Copy Number Is a Common Feature of Genes Upregulated in GC Cases Having wt CDH1 Sequence
3.6. CDH1 Mutation in DGC Entails Gene Enrichment of Bmp2, Stem Cell, and H3K27me3 Pathways for Upregulated Genes and DREAM Complex, Targets of EWSR1-FLI1 Fusion up and BRCA1 PCC Network Pathways for Downregulated Genes
3.7. Protein-Encoding Isoforms of Genes Associated with CDH1 Genomic Alterations in GC
3.8. CDH1 Transcriptional Levels and Degree of DNA Methylation Are Inversely Correlated in GC Subtypes
3.9. A Set Comprising 50 of the Most Upregulated Genes in CDH1-Mutated GC Cases Associate with Lower Overall Survival of GC Patients
3.10. Therapeutic Implications of CDH1-Associated Transcriptional Changes in GC
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Symbol | FC * | p-Value | Function in GC or in General | Reference * |
---|---|---|---|---|
TMEM119 | 2.44 | 3.0 × 10−8 | STAT3 signaling in GC. | Zheng P et al. Onco Targets Ther 2018 [34] |
COL16A1 | 1.83 | 1.4 × 10−7 | Cell attachment and integrin-mediated cellular reactions. | Nd |
OMD | 3.45 | 1.6 × 10−7 | Biomineralization processes. TGFbeta pathway. | Nd |
PRRX1 | 1.96 | 2.2 × 10−7 | WNT-related cofactor of EMT in GC. | Guo J Et al. Mol Oncol 2015 [35] |
PCOLCE | 2.05 | 3.0 × 10−7 | Immune infiltration in GC. | Xiang A et al. Front Mol BioSci 2020 [36] |
EMILIN1 | 1.98 | 3.0 × 10−7 | Extracellular matrix glycoprotein interacting with microfibrils and collagens. Angiogenesis, migration, invasion in GC. | Qi Y et al. BMC Cancer 2019 [37] |
CYP1B1 | 3.32 | 3.3 × 10−7 | Cytochrome P450, aryl hydrocarbon receptor pathway in GC. | Yin XF et al. Oncol Rep 2013 [38] |
S1PR2 | 1.47 | 4.6 × 10−7 | Bile acid receptors, gastrointestinal functions. | Ticho AL et al. Liver Res 2019 [39] |
GAS1 | 2.33 | 4.8 × 10−7 | Stem cell activity in GC. | Katano T et al. Am. J. Pathol. 2015 [40] |
CLMP | 2.07 | 7.5 × 10−7 | Cell–cell adhesion. | Nd |
KCNE4 | 2.00 | 8.5 × 10−7 | Subunit of the voltage-gated potassium channel complex. | Nd |
COL6A2 | 1.84 | 8.7 × 10−7 | Cell-binding protein. | Nd |
CCDC80 | 2.80 | 9.8 × 10−7 | Cell adhesion. | Nd |
FMNL3 | 1.65 | 1.0 × 10−6 | Required in the control of cell shape and migration. RHO-GTPase related. | Nd |
VSTM4 | 1.98 | 1.0 × 10−6 | V-Set and Transmembrane Domain Containing. | Nd |
PCDHGB7 | 1.80 | 1.1 × 10−6 | Expressed in liver and pancreatic juice. | Nd |
CILP | 2.53 | 1.1 × 10−6 | TGFbeta and IGF1 pathway control. | Nd |
CCDC8 | 1.68 | 1.1 × 10−6 | Cofactor required for p53-mediated apoptosis. Interacts with JMJD2A. | Nagakawa T et al. Gastric Cancer 2020 [41] |
CFD | 2.93 | 1.2 × 10−6 | Complement Factor D. | Nd |
BNC2 | 2.41 | 1.2 × 10−6 | Zinc finger protein, mutated in GC. | Yang M Arai et al. Carcinogenesis 2020 [42] |
POU2AF1 | 1.75 | 1.4 × 10−6 | Transcriptional coactivator of OCT1 or OCT2 | Nd |
SERPINF1 | 2.40 | 1.4 × 10−6 | Secreted by adipocytes. | Nd |
RUNX1T1 | 2.18 | 1.5 × 10−6 | Inhibitor of CEBPB. Downregulated in 38 % of GC. | Regalo G et al. J Mol Med 2016 [43] |
COL6A3 | 1.84 | 1.5 × 10−6 | Upregulated in GC. Its inhibition blocks cancer cell proliferation. | Yang B et al. Front Genet 2020 [44] |
GGT5 | 1.92 | 1.6 × 10−6 | Inhibits steoroidogenesis. Member of the metabolic signature of GC. | Zhao Q et al. J Cancer 2021 [45] |
HIC1 | 2.03 | 1.8 × 10−6 | Transcriptional repressor in Wnt signaling. | Nd |
COLEC12 | 2.15 | 1.8 × 10−6 | Receptor involved in H. Pylori-stromal cell interaction in gastric diseases. | Chang LL et al. Sci Rep 2018 [46] |
THBS4 | 3.54 | 1.9 × 10−6 | Promotes proliferation and metastasis in GC. | Chen X et al. J Physiol Biochem 2019 [47] |
GLIPR2 | 1.57 | 1.9 × 10−6 | Glioma Pathogenesis-Related Protein 2. Protein binding in vesicle. | Nd |
COL8A2 | 1.82 | 1.9 × 10−6 | Migration and proliferation of vascular smooth muscle cells. Induced by TWIST1. | Nd |
GLI1 | 2.29 | 2.0 × 10−6 | Regulates stemness characteristics in GC. | Qi W et al. Diagn Pathol 2020 [48] |
ZEB2 | 1.90 | 2.2 × 10−6 | Transcriptional inhibitor that represses CDH1. | Park JW et al. Mol Carcinog 2018 [49] |
CCL19 | 4.40 | 2.4 × 10−6 | Expressed only in GC. Suppresses cell proliferation, migration, and invasion. | Zhou R et al. Human Cell 2020 [50] |
GLI2 | 1.88 | 2.4 × 10−6 | GLI2 induces PDGFRB expression and modulates cancer stem cells in GC. Involved in resistance to drugs in GC. | Lu Y et al. J Transl Med 2021 [51] |
RFTN1 | 1.59 | 2.4 × 10−6 | Formation and/or maintenance of lipid rafts. | Nd |
ADRA2A | 1.93 | 2.4 × 10−6 | The stimulation of this adrenoceptor enhances gastric carcinogenesis. | Tatsuta M et al. Int J Can 1998 [52] |
GLT8D2 | 1.86 | 2.6 × 10−6 | Glycosyltransferase 8 Domain Containing 2. Synthetic lethal with Ras | Nd |
TIMP3 | 2.06 | 2.7 × 10−6 | Metalloprotease inhibitor. Tissue-specific acute response to remodeling stimuli. Marker of GC. | George S et al. Front Microbiol 2020 [53] |
ASPN | 2.14 | 2.7 × 10−6 | Promotes cell proliferation via PSMD2. Overexpressed in DGC. | Zhang Z et al. Front Biosci 2019 [54] |
MAP1A | 2.00 | 2.8 × 10−6 | Binding partner of RhoB. Regulator of EGFR. | Nd |
FBLN2 | 2.26 | 2.9 × 10−6 | Required for basement membrane integrity. | Nd |
DTX1 | 2.17 | 3.0 × 10−6 | Regulation of c-FLIP stability. Downregulated in GC. | Hsu TS et al. Cell Death Dis 2018 [55] |
BCL2 | 1.92 | 3.3 × 10−6 | Antiapoptotic protein never mentioned as associated to CDH1 mutations in GC. | Nd |
BOC | 2.70 | 3.4 × 10−6 | Positively regulates hedgehog signaling. | Nd |
LSP1 | 1.82 | 3.4 × 10−6 | Lymphocyte and endothelium specific. | Nd |
PLEKHO2 | 1.52 | 3.6 × 10−6 | Promotes macrophages survival. | Nd |
TMEM273 | 1.75 | 3.7 × 10−6 | Uncharacterized protein. | Nd |
OLFML1 | 1.95 | 3.7 × 10−6 | Olfactomedin-Like Protein 1. | Nd |
TWIST2 | 2.25 | 3.7 × 10−6 | Vascuologenic mimicry. EMT in GC. | Wang L et al. Oncotarget 2015 [56] |
SSC5D | 2.10 | 3.7 × 10−6 | Scavenger Receptor Cysteine-Rich Family Member With 5 Domains. | Nd |
Gene | FC * | p-Value | Function in GC or in General | Reference * |
---|---|---|---|---|
C5orf34 | 1.85 | 5.2 × 10−7 | Uncharacterized protein. | Nd |
SQLE | 2.13 | 5.7 × 10−7 | Squalene epoxidase. Rate-limiting enzyme in steroid biosynthesis. | Nd |
EIF2S2 | 1.47 | 1.0 × 10−6 | Eukaryotic translation initiation factor 2. | Nd |
TOMM34 | 1.64 | 1.2 × 10−6 | Unfolded protein import in mitochondria. | Nd |
RAE1 | 1.54 | 1.2 × 10−6 | RNA exporting to cytoplasm. | Nd |
LINC00511 | 2.04 | 1.2 × 10−6 | Acts as a ceRNA in GC | Sun CB et al. World J Gastr Oncol 2020 [63] |
HSD17B7 | 1.45 | 1.4 × 10−6 | Hydroxysteroid 17-Beta Dehydrogenase 7. Mevalonate and sterols enzyme downregulated and associated with survival in GC. | Chang W-C et al. Cancer Med 2018 [64] |
TOP2A | 2.22 | 1.8 × 10−6 | DNA Topoisomerase II Alpha. Associated with GC recurrence. | Terashima MI et al. Oncotarget 2017 [65] |
DHCR7 | 1.89 | 1.9 × 10−6 | Removes the C [7,8] double bond of sterols and catalyzes the conversion of 7-dehydrocholesterol to cholesterol. | Nd |
DNMT3B | 2.70 | 2.0 × 10−6 | DNA Methyltransferase 3 Beta. Its downregulation induces stemness. | Wu S et al. Biosci Rep 2020 [66] |
MAL2 | 1.75 | 2.0 × 10−6 | Marker of spasmolytic polypeptide expressing metaplasia of stomach. | Weis VG et al. Am J Physiol Gastr Liver Physiol 2014 [67] |
CCT6A | 1.52 | 2.1 × 10−6 | Molecular chaperon. Member of the TCP1 ring complex. | Nd |
RFC3 | 1.79 | 2.2 × 10−6 | Replication factor. Its downregulation associates with MSI in GC. | Kim HR et al. Hum Pathol 2010 [68] |
PRMT3 | 1.47 | 2.7 × 10−6 | Arginine methyltransferases. Modifying enzyme of histones. | Nd |
NELFCD | 1.61 | 3.5 × 10−6 | Member of the negative elongation factor complex. | Nd |
ATAD2 | 1.69 | 4.8 × 10−6 | ATPase, oncogene overexpressed in GC. | Zhang M et al. Clin Transl Oncol 2016 [69] |
IDI1 | 1.56 | 5.2 × 10−6 | Enzyme involved in the synthesis of farnesyl diphosphate and cholesterol. | Nd |
EFNA1 | 1.75 | 5.7 × 10−6 | Ligand for Eph receptors. Negative regulator in tumorigenesis via EPHA2 and FAK in GC. | Lee PC et al. Oncogene 2020 [70] |
CSE1L | 1.54 | 5.8 × 10−6 | Mediator of cellular proliferation, invasion, and apoptosis via upregulation of MTIF activity in GC. | Li Y et al. J Cell Physiol 2020 [71] |
TPX2 | 1.82 | 6.0 × 10−6 | Spindle assembly factor upregulated in GC. | Huang J et al. Biomark Med 2020 [72] |
GPR89B | 1.45 | 6.3 × 10−6 | Voltage dependent anion channel required for acidification and functions of the Golgi apparatus. | Nd |
NUF2 | 1.72 | 7.1 × 10−6 | Component of the essential kinetochore-associated NDC80 complex. | Nd |
UBE2C | 2.00 | 7.5 × 10−6 | Marker of microsatellite instability in the intestinal GC type. | Wang R et al. Int J Oncol 2017 [73] |
CDK1 | 1.64 | 1.0 × 10−5 | Contributes to colony-forming ability of gastric cancer cells. | Li F et al. Int J Biol Sci 2021 [74] |
DDX27 | 1.52 | 1.1 × 10−5 | Contributes to colony-forming ability of gastric cancer cells. | Jin Y et al. Front Genet 2022 [75] |
TMEM14A | 1.45 | 1.3 × 10−5 | Expression upregulated and correlated to worse prognosis in ovarian cancer. | Zhang X et al. Front Cell Dev Biol 2020 [76] |
PDRG1 | 1.49 | 1.4 × 10−5 | p53 and DNA damage-regulated gene upregulated in GC. | Zhang Y-J et al. Pathol Res Pract 2019 [77] |
HIST1H2BD | 2.08 | 1.6 × 10−5 | Core component of nucleosome. | Nd |
MSMO1 | 1.64 | 1.8 × 10−5 | Methylsterol Monooxygenase 1. Enzyme of the cholesterol biosynthesis. | Nd |
ETV4 | 2.33 | 1.9 × 10−5 | ETV4 promotes the progression of gastric cancer through regulating KDM5D. | Cai L-S et al. Eur Rev Med Pharmacol Sci 2020 [78] |
AURKA | 1.89 | 1.9 × 10−5 | Mitotic serine/threonine kinase overexpressed in GC | Orenay-Boyacioglu S et al. Mol Biol Rep 2018 [79] |
MTBP | 1.64 | 2.0 × 10−5 | MDM2-binding protein downregulated in GC. | Wang W et al. Oncol Lett 2017 [80] |
MRGBP | 1.56 | 2.1 × 10−5 | Component of the NuA4 histone acetyltransferase complex | Nd |
GGH | 2.5 | 2.2 × 10−5 | Gamma-Glutamyl Hydrolase enzyme. | Nd |
TDRKH | 1.67 | 2.4 × 10−5 | Catalyze the final steps of primary piRNA biogenesis | Nd |
HIST1H3H | 2.5 | 2.5 × 10−5 | Core component of nucleosome. | Nd |
RPN2 | 1.45 | 2.9 × 10−5 | Subunit of the oligosaccharyl transferase complex. Multidrug resistance associated factor in GC. | Zhang H et al. Int J Biol Macromol 2019 [81] |
RAB5IF | 1.45 | 3.0 × 10−5 | Assembly factor for mitochondrial respiratory complexes. | Nd |
RAD54B | 1.61 | 3.2 × 10−5 | DNA repair and risk factor in GC. | Li W-Q et al. Carcinogenesis 2013 [82] |
GAD1 | 4.17 | 3.5 × 10−5 | Glutamic acid decarboxylase involved in GC. | Song Y et al. Histopathology 2013 |
POLE2 | 1.54 | 3.6 × 10−5 | DNA Polymerase Epsilon 2. | Nd [83] |
KRT80 | 3.12 | 4.3 × 10−5 | Activated by lncRNA CircPIP5K1A in GC. | Song H et al. Biomed Pharmacother 2020 [84] |
CPNE1 | 1.56 | 4.5 × 10−5 | Calcium-dependent phospholipid-binding protein. | Nd |
ACAT2 | 1.47 | 4.6 × 10−5 | Cytosolic acetoacetyl-CoA thiolase. | Nd |
DCAF13 | 1.47 | 5.2 × 10−5 | Ribosomal RNA processing. | Nd |
PRELID3B | 1.52 | 5.6 × 10−5 | PRELI Domain Containing 3B. | Nd |
CMTM8 | 1.61 | 5.7 × 10−5 | Chemokine-like factor downregulated in solid tumors | Nd |
KIF14 | 1.56 | 5.9 × 10−5 | Promotes tumor progression in GC. | Yang Z et al. BBA Mol Basis Dis 2019 [85] |
CKS1B | 1.49 | 6.8 × 10−5 | Cyclin dependent kinases regulator involved in intestinal GC | Zhang J et al. Front Pharmacol 2018 [86] |
CHKA | 1.61 | 7.4 × 10−5 | Choline Kinase Alpha | Nd |
Genes | FC * | p-Value | Function in GC or in General | Reference * |
---|---|---|---|---|
Upregulated | ||||
PCDHA7 | 1.57 | 2.2 × 10−5 | Protocadherin Alpha 7, neuronal. | Nd |
CD93 | 1.49 | 6.4 × 10−5 | Receptor for C1q. Mannose-binding protein. | Nd |
XAB2 | 1.61 | 8.7 × 10−5 | SNPs are associated with GC. | Xie Y et al. Int J Res Publ Health 2021 [87] |
SGSM1 | 1.52 | 1.6 × 10−4 | Small G Protein Modulator of RAB family | Nd |
TRPC7 | 1.52 | 4.0 × 10−4 | Transient Receptor Potential Cation Channel Subfamily C Member 7 | Nd |
BRINP3 | 1.47 | 5.1 × 10−4 | Hypermethylated and downregulated in pre-GC and GC. | Chen L et al. Dis Markers 2012 [88] |
ADAMTSL4 | 1.57 | 6.1 × 10−4 | Disintegrin and metalloproteinase with thrombospondin motifs. Positive regulation of apoptosis. | Nd |
STAMBPL1 | 1.59 | 1.0 × 10−3 | STAMBPL1 knockdown inhibits GC. | Yu D-J et al. Oncol Lett 2019 [89] |
TAOK1 | 1.67 | 1.5 × 10−3 | Kinase involved in p38/MAPK14 stress-activated MAPK cascade. Negative regulator of inflammation. | Nd |
TADA2B | 1.61 | 1.7 × 10−3 | Coactivates PAX5-dependent transcription together with either SMARCA4 or GCN5L2 | Nd |
PABPC3 | 1.5 | 1.8 × 10−3 | Binds the poly[A] tail of mRNA. | Nd |
ATP8B1 | 1.46 | 1.8 × 10−3 | Catalytic component of a P4-ATPase flippase complex. | Nd |
ADAM22 | 1.49 | 2.0 × 10−3 | Non-catalytic metalloprotease-like protein, neuronal. Regulator of cell adhesion, spreading, inhibition of cell proliferation | Nd |
POU5F2 | 1.71 | 2.0 × 10−3 | Transcription factor required for terminal differentiation of male germ cell. | Nd |
P3H1 | 1.59 | 2.1 × 10−3 | Basement membrane-associated chondroitin sulfate proteoglycan with prolyl 3-hydroxylase activity. | Nd |
SMARCA4 | 1.45 | 2.1 × 10−3 | Loss of chromatin remodeling SMARCA4 associated to GC subtypes. | Huang S-C et al. Histopathology 2020 [90] |
KCNV2 | 1.48 | 2.2 × 10−3 | Voltage-gated potassium [Kv] channels subunit. | Nd |
FAM193A | 1.44 | 2.3 × 10−3 | Uncharacterized protein. | Nd |
MOCOS | 1.53 | 2.4 × 10−3 | Sulfurates the molybdenum cofactor. | Nd |
UBA6 | 1.77 | 2.4 × 10−3 | Required for UBD/FAT10 conjugation. | Nd |
KIAA1683 | 1.47 | 2.5 × 10−3 | Alias of IQCN. Uncharacterized protein. | Nd |
TROAP | 1.48 | 2.7 × 10−3 | Cell adhesion. Its downregulation inhibits cell proliferation of GC. | Jing K et al. Mol Med Rep 2018 [91] |
CDH16 | 1.45 | 2.7 × 10−3 | Cadherin 16, associated to renal oncocytoma. | Nd |
DHX35 | 1.6 | 2.7 × 10−3 | DEAD box proteins, putative RNA helicases. | Nd |
SMC3 | 1.57 | 2.7 × 10−3 | Cohesin, required for cell cycle. | Nd |
GAD1 | 1.5 | 2.8 × 10−3 | Glutamic acid decarboxylase involved in GC | Song Y et al. Histopathology 2013 [83] |
MAP3K6 | 1.46 | 3.0 × 10−3 | Germline mutations are associated with familial GC. | Gaston D et al. PloS Genet 2014 [92] |
ZNF418 | 1.61 | 3.1 × 10−3 | Its overexpression is protective to GC. | Hui H-X et al. Onco Target Ther 2018 [93] |
RBM22 | 1.80 | 3.1 × 10−3 | Component of spliceosome. | Nd |
FMNL2 | 1.62 | 3.2 × 10−3 | Formin member, morphogenesis. FMNL2 silencing inhibits GC. | Zhong B et al. Cancer Cell Int 2018 [94] |
IFFO1 | 1.73 | 3.3 × 10−3 | Nuclear matrix intermediate filament. | Nd |
KIAA0556 | 1.49 | 3.3 × 10−3 | Alias of KATNIP. Katanin Interacting ciliary protein. | Nd |
MAP4K4 | 1.47 | 3.4 × 10−3 | MAP kinase upstream to JUN pathway. Its silencing suppresses GC proliferation. | Liu YF et al. Mol Med Rep 2016 [95] |
NETO2 | 1.47 | 3.7 × 10−3 | Subunit of neuronal ainite-sensitive glutamate. Promotes GC invasion. | Liu JY et al. Cell Death Dis 2019 [96] |
TBPL2 | 1.56 | 3.7 × 10−3 | Transcription factor required for myocytes differentiation. | Nd |
DIAPH1 | 1.5 | 3.8 × 10−3 | Formin-related, cell morphology, and cytoskeletal. | Nd |
LPCAT3 | 1.68 | 3.8 × 10−3 | Lysophospholipid O-acyltransferase. | Nd |
ELP3 | 1.56 | 3.8 × 10−3 | Catalytic subunit of the histone acetyltransferase elongator complex. | Nd |
ZFP57 | 1.52 | 3.9 × 10−3 | Zinc finger protein required to maintain maternal and paternal gene imprinting. | Nd |
FGF21 | 2.14 | 4.0 × 10−3 | Fibroblast growth factor. Serum marker of GC. | Kimak E et al. Pol Arch Intern Med 2019 [97] |
ZMPSTE24 | 1.62 | 4.0 × 10−3 | Zinc metalloproteinase in lamin A pathway. Involved in MSI-H GC. | Lee JH et al. Pathol Res Pract 2016 [98] |
EEF1D | 1.60 | 4.2 × 10−3 | Subunit of the elongation factor 1 complex. | Nd |
GABBR2 | 1.45 | 4.2 × 10−3 | Component of a heterodimeric G-protein coupled receptor for GABA. | Nd |
SGCE | 1.60 | 4.2 × 10−3 | Component of the sarcoglycan complex. Predicts prognosis of GC. | Hou J-Y et al. J Cancer Res Clin Oncol 2017 [99] |
SMARCB1 | 1.53 | 4.2 × 10−3 | Chromatin remodeling protein involved in GC. | Mochizuki K et al. Anticancer Res 2018 [100] |
NR0B2 | 2.23 | 4.3 × 10−3 | Inhibitor of transactivation of nuclear receptors. | Nd |
ATN1 | 1.47 | 4.4 × 10−3 | Transcriptional corepressor. Recruits NR2E1 to repress transcription. | Nd |
HPR | 1.82 | 4.4 × 10−3 | Haptoglobin-related protein. | Nd |
ECT2L | 1.47 | 4.5 × 10−3 | Guanine nucleotide exchange factor. | Nd |
CYP2U1 | 1.56 | 4.6 × 10−3 | Cytochrome P450 monooxygenase, metabolism of arachidonic acid. | Nd |
ITPRID2 | 1.44 | 4.6 × 10−3 | Unknown | Nd |
Downregulated | ||||
CDH1 | 1.49 | 1.2 × 10−4 | Cadherine 1, calcium-dependent cell–cell adhesion glycoprotein | Guilford P et al. Nature 1998 [101] |
Library | Gene Set | LogFC * | p. Value | Adj p. Value * |
---|---|---|---|---|
TRRUST_Transcription_Factors_2019 | SNAI2 mouse | 0.14 | 1.58 × 10−24 | 6.83 × 10−21 |
ARCHS4_TFs_Coexp | EHF human tf ARCHS4 coexpression | 0.14 | 1.60 × 10−24 | 6.83 × 10−21 |
ARCHS4_TFs_Coexp | TFCP2L1 human tf ARCHS4 coexpression | 0.12 | 1.14 × 10−23 | 2.92 × 10−20 |
ARCHS4_TFs_Coexp | OVOL2 human tf ARCHS4 coexpression | 0.11 | 1.37 × 10−23 | 2.92 × 10−20 |
RNAseq_Automatic_GEO_Signatures_Mouse_Down | Ago2 Sufficent Pancreatic Lsl GSE147781 1 | 0.13 | 4.94 × 10−24 | 4.20 × 10−20 |
ARCHS4_TFs_Coexp | GRHL2 human tf ARCHS4 coexpression | 0.13 | 7.55 × 10−23 | 1.29 × 10−19 |
RNAseq_Automatic_GEO_Signatures_Human_Down | Ogt Knockout S2Vp10 Cells GSE114472 1 | 0.11 | 1.16 × 10−22 | 3.69 × 10−19 |
RNAseq_Automatic_GEO_Signatures_Mouse_Down | Kras Rank Rankfl Pneumocytes GSE81670 1 | 0.10 | 1.30 × 10−22 | 3.69 × 10−19 |
ARCHS4_Kinases_Coexp | ERBB3 human kinase ARCHS4 coexpression | 0.14 | 9.90 × 10−23 | 3.82 × 10−19 |
ARCHS4_TFs_Coexp | KLF5 human tf ARCHS4 coexpression | 0.14 | 2.97 × 10−22 | 4.02 × 10−19 |
ARCHS4_TFs_Coexp | ELF3 human tf ARCHS4 coexpression | 0.12 | 3.30 × 10−22 | 4.02 × 10−19 |
CellMarker_Augmented_2021 | Flk1 + Mesodermal cell:Pluripotent Stem Cell | 0.11 | 2.84 × 10−21 | 1.09 × 10−18 |
ARCHS4_IDG_Coexp | FXYD3 IDG ionchannel ARCHS4 coexpression | 0.13 | 4.25 × 10−22 | 4.44 × 10−18 |
TRRUST_Transcription_Factors_2019 | ZEB1 human | 0.13 | 4.93 × 10−21 | 4.89 × 10−18 |
ARCHS4_TFs_Coexp | MST1R human tf ARCHS4 coexpression | 0.15 | 5.16 × 10−21 | 4.89 × 10−18 |
ARCHS4_Kinases_Coexp | STYK1 human kinase ARCHS4 coexpression | 0.13 | 2.02 × 10−21 | 5.84 × 10−18 |
Reactome_2016 | Signaling by MST1 Homo sapiens R-I−8852405 | 0.17 | 3.20 × 10−21 | 7.41 × 10−18 |
ENCODE_TF_ChIP-seq_2015 | ZEB1 HepG2 hg19 | 0.10 | 9.58 × 10−21 | 8.19 × 10−18 |
ARCHS4_Kinases_Coexp | MST1R human kinase ARCHS4 coexpression | 0.15 | 5.45 × 10−21 | 1.05 × 10−17 |
RNAseq_Automatic_GEO_Signatures_Human_Up | Runx Transciption Factor Mediated GSE141503 1 | 0.09 | 2.78 × 10−20 | 2.81 × 10−17 |
RNAseq_Automatic_GEO_Signatures_Human_Down | Re-Induction Baruch Science 2020 GSE162436 2 | 0.13 | 2.99 × 10−20 | 2.81 × 10−17 |
ARCHS4_TFs_Coexp | OVOL1 human tf ARCHS4 coexpression | 0.12 | 4.05 × 10−20 | 3.15 × 10−17 |
ARCHS4_IDG_Coexp | TMC4 IDG ionchannel ARCHS4 coexpression | 0.11 | 1.30 × 10−20 | 4.53 × 10−17 |
RNAseq_Automatic_GEO_Signatures_Mouse_Up | Elf5 C3-T Elf5-Gfp Reporter GSE122180 1 | 0.10 | 9.19 × 10−20 | 7.42 × 10−17 |
InterPro_Domains_2019 | BRO1 domain | 0.15 | 7.38 × 10−20 | 9.82 × 10−17 |
Pfam_Domains_2019 | BRO1 | 0.15 | 7.38 × 10−20 | 9.82 × 10−17 |
InterPro_Domains_2019 | Growth factor receptor domain 4 | 0.14 | 7.42 × 10−20 | 9.82 × 10−17 |
Pfam_Domains_2019 | GF recep IV | 0.14 | 7.42 × 10−20 | 9.82 × 10−17 |
BioPlex_2017 | APOB | 0.12 | 6.71 × 10−20 | 1.11 × 10−16 |
GTEx_Tissue_Sample_Gene_Expression_Profiles_up | GTEX-SNMC−0626-SM−4DM6H stomach male 20–29 years | 0.11 | 1.05 × 10−18 | 1.12 × 10−16 |
ARCHS4_Kinases_Coexp | PTK6 human kinase ARCHS4 coexpression | 0.11 | 9.25 × 10−20 | 1.34 × 10−16 |
RNAseq_Automatic_GEO_Signatures_Mouse_Down | Kras Hdac5 Eccaper Pdac GSE149126 1 | 0.10 | 2.26 × 10−19 | 1.59 × 10−16 |
InterPro_Domains_2019 | MANSC domain | 0.14 | 1.87 × 10−19 | 2.06 × 10−16 |
ARCHS4_TFs_Coexp | ZBTB7C human tf ARCHS4 coexpression | 0.10 | 3.88 × 10−19 | 2.75 × 10−16 |
ARCHS4_TFs_Coexp | LGR4 human tf ARCHS4 coexpression | 0.10 | 4.19 × 10−19 | 2.75 × 10−16 |
RNAseq_Automatic_GEO_Signatures_Human_Up | Overexpression Proliferation Drivers Mammary GSE109326 4 | 0.11 | 8.36 × 10−19 | 4.89 × 10−16 |
ENCODE_and_ChEA_Consensus_TFs_from_ChIP-X | ZEB1 ENCODE | 0.10 | 1.18 × 10−18 | 7.19 × 10−16 |
Pfam_InterPro_Domains | Aminotrans I/II | 0.11 | 8.89 × 10−19 | 8.41 × 10−16 |
ARCHS4_IDG_Coexp | SCNN1B IDG ionchannel ARCHS4 coexpression | 0.10 | 4.10 × 10−19 | 1.07 × 10−15 |
BioPlex_2017 | ITM2A | 0.12 | 8.80 × 10−19 | 1.13 × 10−15 |
Drug_Perturbations_from_GEO_2014 | vitamin c mus musculus gpl6246 gse19378 chdir up | 0.07 | 9.42 × 10−19 | 3.20 × 10−15 |
Gene Symbol-Isoform | Gene ID ENST | Tumor mRNA * | Normal mRNA * | Adjusted p-Value | Characteristics [aa Length vs. Refseq] |
---|---|---|---|---|---|
From Table 1 | |||||
ASPN−002 | 00000375543 | 1.2 | 0.01 | 2.95 × 10−30 | Unique 243 aa vs. 380 aa |
CCDC80-006 | 00000479368 | 0.001 | 1.57 | 5.27 × 10−35 | Unique 212 aa vs. 950 aa |
CCDC80-007 | 00000461431 | 0.15 | 1.70 | 1.13 × 10−33 | Unique 261 aa vs. 950 aa |
COL16A1-013 | 00000458715 | 1.43 | 4.66 | 5.04 × 10−22 | Unique 235 aa vs. 1604 aa |
COL6A3-012 | 00000472056 | 60.97 | 11.93 | 6.61 × 10−22 | Unique 2570 aa vs. 3177 aa |
COL6A3-202 | 00000353578 | 9.02 | 0.38 | 3.61 × 10−66 | Unique 2971 aa vs. 3177 aa |
FBLN2-002 | 00000295760 | 8.85 | 2.59 | 1.70 × 10−14 | Unique 1184 aa vs. 1231 aa |
PRRX1-001 | 00000367760 | 1.53 | 0.12 | 5.67 × 10−33 | Unique 217 aa vs. 245 aa |
From Table 2 | |||||
AURKA-007 | 00000456249 | 1.08 | 0.01 | 5.44 × 10−37 | Unique 106 aa vs. 403aa |
GGH-003 | 00000518113 | 1.72 | 0.22 | 3.10 × 10−30 | Unique 271 aa vs. 318 aa |
PRMT3-002 | 00000330796 | 2.62 | 0.64 | 5.90 × 10−36 | Shared 46 aa vs. 531aa |
RAE1-009 | 00000527947 | 9.34 | 3.17 | 8.08 × 10−29 | Unique 437 aa vs. 368 aa |
UBE2C-003 | 00000335046 | 1.02 | 0,01 | 8.98 × 10−48 | Unique 161 aa vs. 179 aa |
UBE2C-004 | 00000372568 | 3.84 | 0.15 | 5.29 × 10−64 | Unique 140 aa vs. 179 aa |
UBE2C-006 | 00000352551 | 3.13 | 0.01 | 8.42 × 10−56 | Unique 150 aa vs. 179 aa |
From Table 3 | |||||
ANXA4-002 | 00000409920 | 33.15 | 9.56 | 1.7 × 10−17 | Unique 299 aa vs. 321 aa |
ARHGEF28-006 | 00000512883 | 0.46 | 3.34 | 5.4 × 10−31 | Unique 651 aa vs. 1731 aa |
DSC2-002 | 00000251081 | 10.07 | 2.07 | 1.31 × 10−13 | Unique 847 aa vs. 901 aa |
EEF1D-019 | 00000529516 | 9.92 | -3.44 | 1.64 × 10−93 | Shared 262 aa vs. 647 aa |
EEF1D-045 | 00000533494 | 0.49 | 1.48 | 1.14 × 10−36 | Shared 281aa vs. 647 aa |
ELP3-003 | 00000524103 | 1.46 | 0.01 | 6.09 × 10−20 | Unique 475 aa vs. 547 aa |
ELP3-004 | 00000518112 | 2.95 | 0.37 | 1.13 × 10−40 | Shared 45 aa vs. 547 aa |
EPB41L1-003 | 00000427533 | 2.28 | 0.32 | 2.43 × 10−36 | Unique 59 aa vs. 1595 aa |
EPB41L1-012 | 00000432603 | 12.10 | 2.68 | 2.68 × 10−49 | Unique 119 aa vs. 1595 aa |
EPB41L1-015 | 00000406771 | 8.52 | 2.01 | 1.65 × 10−33 | Unique 168 aa vs. 1595 aa |
EPB41L1-016 | 00000628415 | 11.35 | 4.96 | 5.9 × 10−26 | Unique 701 aa vs. 1595 aa |
FBXO38-201 | 00000296701 | 1.14 | 0.01 | 3.8 × 10−13 | Shared 943 aa vs. 1188 aa |
KIF18B-002 | 00000587309 | 5.02 | 0.24 | 2.05 × 10−77 | Unique 833 aa vs. 852 aa |
MAP4K4-001 | 00000347699 | 5.25 | 0.01 | 4.46 × 10−44 | Unique 1239 aa vs. 1273 aa |
MUC20-001 | 00000447234 | 4.96 | 0.15 | 1.07 × 10−29 | Unique 709 aa vs. 723 aa |
MUC20-201 | 00000320736 | 18.33 | 3.75 | 3.86 × 10−14 | Unique 538 aa vs. 723 aa |
P3H1-001 | 00000296388 | 11.09 | 2.31 | 1.56 × 10−74 | Unique 736 aa vs. 804 aa |
P3H1-201 | 00000397054 | 1.49 | 0.19 | 1.72 × 10−59 | Unique 697 aa vs. 804 aa |
SGCE-002 | 00000437425 | 0.62 | 2.31 | 6.66 × 10−20 | Unique 396 aa vs. 473 aa |
SMARCA4-003 | 00000444061 | 9.89 | 2.68 | 2.24 × 10−56 | Shared 1613 aa vs. 1647 aa |
TMEM132A-010 | 00000544065 | 1.6 | 0.01 | 6.88 × 10−27 | Unique 76 aa vs. 1023 aa |
TROAP-001 | 00000257909 | 4.46 | 0.25 | 1.41 × 10−79 | Unique 778 aa vs. 868 |
TROAP-002 | 00000380327 | 1.06 | 0.01 | 2.29 × 10−33 | Unique 144 aa vs. 868 |
TROAP-005 | 00000548311 | 2.96 | 0.16 | 4.11 × 10−52 | Shared 126 aa vs. 868 aa |
TROAP-009 | 00000550709 | 1.19 | 0.09 | 4.87 × 10−31 | Shared 126 aa vs. 868 aa |
UBA6-005 | 00000505673 | 2.35 | 0.26 | 9.77 × 10−23 | Unique 271 aa vs. 1052 aa |
USP22-003 | 00000476111 | 16.16 | 0.01 | 1.53 × 10−42 | Unique 125 aa vs. 525 aa |
USP22-005 | 00000537526 | 0.06 | 18.48 | 3.73 × 10−66 | Unique 513 aa vs. 525 aa |
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Malpeli, G.; Barbi, S.; Innamorati, G.; Alloggio, M.; Filippini, F.; Decimo, I.; Castelli, C.; Perris, R.; Bencivenga, M. Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer. J. Pers. Med. 2022, 12, 2006. https://doi.org/10.3390/jpm12122006
Malpeli G, Barbi S, Innamorati G, Alloggio M, Filippini F, Decimo I, Castelli C, Perris R, Bencivenga M. Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer. Journal of Personalized Medicine. 2022; 12(12):2006. https://doi.org/10.3390/jpm12122006
Chicago/Turabian StyleMalpeli, Giorgio, Stefano Barbi, Giulio Innamorati, Mariella Alloggio, Federica Filippini, Ilaria Decimo, Claudia Castelli, Roberto Perris, and Maria Bencivenga. 2022. "Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer" Journal of Personalized Medicine 12, no. 12: 2006. https://doi.org/10.3390/jpm12122006