METHOD FOR PREDICTING EFFICACY OF TREATMENT OF LUNG CANCER PATIENT USING IMMUNE CHECKPOINT INHIBITOR
A method for predicting efficacy of treatment of a lung cancer patient using an immune checkpoint inhibitor includes isolating exosomes from a biological sample derived from the lung cancer patient, and determining an expression level of a protein present in the exosomes by a mass spectrometry method, in which the protein is one or more proteins selected from the group of proteins shown in Table 1-1 to Table 1-6.
1 . A method for predicting efficacy of treatment of a lung cancer patient using with an immune checkpoint inhibitor, the method comprising:
administering the immune checkpoint inhibitor to the lung cancer patient;
taking a biological sample from the lung cancer patient which has been administered with the immune checkpoint inhibitor;
isolating exosomes from the biological sample derived from the lung cancer patient; and
determining an expression level of a protein present in the exosomes by a mass spectrometry method,
wherein the protein is one or more proteins selected from the group of proteins shown in Table 1-1 to Table 1-6:
TABLE 1-1
Protein Name
Band 4.1 -like protein 2
Cullin-2
Protein Hikeshi
Hippocalcin-like protein 1
UTP–glucose-1 -phosphate uridylyltransferase
Attractin
Annexin A3
Rap1 GTPase-activating protein 2
Radixin
Annexin A5
ADP-ribosylation factor 5
L-lactate dehydrogenase B chain
Rho GTPase-activating protein 1
Drebrin
Serine/threonine-protein kinase PAK 2
Protein BRICK1
Integrin alpha-V
Protein kinase C and casein kinase substrate in neurons protein 2
Triokinase/FMN cyclase
Adhesion G-protein coupled receptor G1
Integrin beta-5
Isochorismatase domain-containing protein 1
Septin-2
Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial
Serine/threonine-protein kinase 38
Transient receptor potential cation channel subfamily M member 4
Cytoskeleton-associated protein 5
FAS-associated factor 1
Insulin receptor
Tropomyosin alpha-4 chain
Programmed cell death protein 6
Leukocyte elastase inhibitor
ADP-ribosylation factor 6
Complement component C9
ATP-dependent (S)-NAD(P)H-hydrate dehydratase
Actin, alpha cardiac muscle 1
Heat shock 70 kDa protein 4
14-3-3 protein theta
Phosphatidylinositol transfer protein beta isoform
Phosphoribosyltransferase domain-containing protein 1
Costars family protein ABRACL
Ubiquitin-conjugating enzyme E2 L5
Sodium/potassium-transporting ATPase subunit alpha-1
14-3-3 protein epsilon
TABLE 1-2
Major prion protein
F-actin-capping protein subunit alpha-2
HLA class I histocompatibility antigen, Cw-4 alpha chain
GTP-binding protein SAR1a
Actin-related protein ⅔ complex subunit 5
Glutathione reductase, mitochondrial
Guanine nucleotide-binding protein subunit alpha-11
Protein disulfide-isomerase A5
MARCKS-related protein
Septin-7
Hsc70-interacting protein
COP9 signalosome complex subunit 8
Vacuolar protein sorting-associated protein 37C
Acidic fibroblast growth factor intracellular-binding protein
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Ribosome maturation protein SBDS
Fructose-bisphosphate aldolase A
BH3-interacting domain death agonist
Charged multivesicular body protein 4b
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
cAMP-dependent protein kinase catalytic subunit alpha
Cytosolic non-specific dipeptidase
Dynamin-1
Neuroplastin
IST1 homolog
Sorting nexin-5
Mitochondrial import inner membrane translocase subunit Tim13
Exocyst complex component 4
Moesin
Serum albumin
Myristoylated alanine-rich C-kinase substrate
Sodium/potassium-transporting ATPase subunit beta-3
Vinculin
Actin-related protein ⅔ complex subunit 1B
Alcohol dehydrogenase class-3
Cysteine and glycine-rich protein 1
E3 ubiquitin-protein ligase TRIM23
Actin-related protein 3
Tetraspanin-15
Ras-related C3 botulinum toxin substrate 1
COP9 signalosome complex subunit 2
Myotrophin
Rho-related GTP-binding protein RhoF
COP9 signalosome complex subunit 3
Glutathione synthetase
DnaJ homolog subfamily C member 5
TABLE 1-3
Glutathione S-transferase omega-1
Glutathione S-transferase Mu 2
Ragulator complex protein LAMTOR2
Cytochrome b5 type B
Progressive ankylosis protein homolog
Septin-11
Rho-associated protein kinase 1
Ras-related C3 botulinum toxin substrate 3
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
Inactive tyrosine-protein kinase transmembrane receptor ROR1
Abl interactor 2
Cell division control protein 42 homolog
Transgelin-2
Ras-related protein Rab-2A
Charged multivesicular body protein 6
ADP-ribosylation factor 3
Glyoxylate reductase/hydroxypyruvate reductase
Profilin-1
Ras-related protein Rab-11 B
Rab GDP dissociation inhibitor alpha
CD97 antigen
Programmed cell death protein 10
Antithrombin-III
F-actin-capping protein subunit beta
Actin-related protein ⅔ complex subunit 2
Twinfilin-2
Ras-related protein Rab-21
Vacuolar-sorting protein SNF8
Caspase-6
Calcineurin subunit B type 1
Extended synaptotagmin-2
Leukocyte surface antigen CD47
COP9signalosomecomplex subunit 1
26S proteasome non-ATPase regulatory subunit 7
Eukaryotic translation initiation factor 3 subunit C-like protein
Deoxycytidylate deaminase
CD276 antigen
Caspase-3
Leucine-rich repeat-containing protein 57
Aldose reductase
Diphosphoinositol polyphosphate phosphohydrolase 1
Coagulation factor XIII A chain
Hsp70-binding protein 1
Sorting nexin-4
Protein phosphatase 1L
Pleckstrin homology domain-containing family N member 1
TABLE 1-4
AP-2 complex subunit alpha-2
Trophoblast glycoprotein
Ras-related protein Rab-23
14-3-3 protein eta
Peroxiredoxin-6
14-3-3 protein beta/alpha
Copine-2
14-3-3 protein gamma
Superoxide dismutase [Cu-Zn]
Microtubule-associated protein RP/EB family member 1
Vasodilator-stimulated phosphoprotein
Phosphoglucomutase-1
Adenylyl cyclase-associated protein 1
Calpain small subunit 1
Dual specificity protein phosphatase 23
Dihydropteridine reductase
Ephrin-B1
Golgin subfamily A member 7
Xaa-Pro aminopeptidase 1
Actin-related protein ⅔ complex subunit 3
Sorting nexin-9
Pleckstrin homology domain-containing family O member 2
WD repeat-containing protein 44
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
COP9 signalosome complex subunit 6
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
Rab-like protein 3
Phosphoacetylglucosamine mutase
Sorting nexin-2
DDB1- and CUL4-associated factor 11
Ras GTPase-activating protein 1
Ribose-5-phosphate isomerase
SHC-transforming protein 1
Glutaminyl-peptide cyclotransferase-like protein
Ras-related protein Rab-5C
Purine nucleoside phosphorylase
Delta-aminolevulinic acid dehydratase
Ras-related protein Rab-5B
Abl interactor 1
Beta-2-glycoprotein 1
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform
Actin-related protein 2
Ras-related protein Rap-2a
Sorcin
Type I inositol 1,4.5-trisphosphate 5-phosphatase
Ras-related protein Rab-35
TABLE 1-5
Rho GTPase-activating protein 18
Ras-related protein Rab-1A
Deoxyribonuclease-1-like 1
Peptidyl-prolyl cis-trans isomerase A
Adenylate kinase isoenzyme 1
Equilibrative nucleoside transporter 1
GTPase NRas
Rho-related GTP-binding protein RhoG
Glycogen phosphorylase, brain form
UV excision repair protein RAD23 homolog B
Omega-amidase NIT2
Serine hydroxymethyltransferase, cytosolic
Sodium/potassium-transporting ATPase subunit beta-1
Endothelial cell-selective adhesion molecule
Isocitrate dehydrogenase [NADP] cytoplasmic
Peptidyl-prolyl cis-trans isomerase FKBP1A
Dystroglycan
Tumor susceptibility gene 101 protein
Peroxiredoxin-5, mitochondrial
Protein XRP2
Actin-related protein ⅔ complex subunit 4
Stathmin
NSFL1 cofactor p47
Folate receptor alpha
Aldo-keto reductase family 1 member A1
Ran-specific GTPase-activating protein
Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform
Vacuolar protein sorting-associated protein VTA1 homolog
Dual specificity protein phosphatase 3
Membrane cofactor protein
Calcium-binding protein 39
Argininosuccinate lyase
Mitochondrial import receptor subunit TOM34
Protein numb homolog
SUMO-conjugating enzyme UBC9
EH domain-containing protein 3
Ras-related protein Rab-1B
Adenine phosphoribosyltransferase
Coronin-1A
Annexin A4
F-actin-capping protein subunit alpha-1
Protein phosphatase 1 regulatory subunit 7
Peflin
Protein/nucleic acid deglycase DJ-1
Ras-related protein Rab-10 Ras-related protein Rap-2b
TABLE 1-6
RNA transcription, translation and transport factor protein
Crk-like protein
Serpin B6
6-phosphogluconolactonase
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Lactadherin
Ras-related protein Ral-A
Protein transport protein Sec23A
Dihydropyrimidinase-related protein 2
NCK-interacting protein with SH3 domain
Vesicle-associated membrane protein 5
Protein phosphatase 1F
Nuclear receptor corepressor 2
Ubiquitin-conjugating enzyme E2 D3
WW domain-binding protein 2
POTE ankyrin domain family member I
Copine-1
Alpha-galactosidase A
Coronin-1B
ATP-dependent RNA helicase DDX1
Ubiquitin-conjugating enzyme E2 K
Syntaxin-binding protein 1
WD repeat-containing protein 37
MOB kinase activator 1B
Nodal modulator 3
Nucleoside diphosphate kinase B
Prostaglandin reductase 1
Phosphoglycerate mutase 2
TLD domain-containing protein 1
Calcium-binding protein 39-like
Glutathione S-transferase LANCL1
Prefoldin subunit 6
Cytosolic phospholipase A2
14-3-3 protein zeta/delta
.
2 . The method according to claim 1 ,
wherein the protein is one or more membrane proteins selected from the group of proteins shown in Table 2:
TABLE 2
Protein Name
Band 4.1-like protein 2
Attractin
Rho GTPase-activating protein 1
Integrin alpha-V
Adhesion G-protein coupled receptor G1
Integrin beta-5
Transient receptor potential cation channel subfamily M member 4
Insulin receptor
Sodium/potassium-transporting ATPase subunit alpha-1
Major prion protein
Fructose-bisphosphate aldolase A
Neuroplastin
Sodium/potassium-transporting ATPase subunit beta-3
Tetraspanin-15
DnaJ homolog subfamily C member 5
Cytochrome b5 type B
Progressive ankylosis protein homolog
Inactive tyrosine-protein kinase transmembrane receptor ROR1
CD97 antigen
Extended synaptotagmin-2
Leukocyte surface antigen CD47
CD276 antigen
Protein phosphatase 1L
Trophoblast glycoprotein
Ephrin-B1
Equilibrative nucleoside transporter 1
Sodium/potassium-transporting ATPase subunit beta-1
Endothelial cell-selective adhesion molecule
Peptidyl-prolyl cis-trans isomerase FKBP1A
Dystroglycan
Folate receptor alpha
Membrane cofactor protein
NCK-interacting protein with SH3 domain
Vesicle-associated membrane protein 5
Syntaxin-binding protein 1
Nodal modulator 3
.
3 . The method according to claim 1 ,
wherein the protein is one or more proteins selected from the group of proteins shown in Table 3:
TABLE 3
Protein Name
Integrin beta-5
Sorting nexin-9
Phosphoacetylglucosamine mutase
Stathm in
Ran-specific GTPase-activating protein
EH domain-containing protein 3
Adenine phosphoribosyltransferase
Protein phosphatase 1 regulatory subunit 7
Nuclear receptor corepressor 2
TLD domain-containing protein 1
Glutathione S-transferase LANCL 1
.
4 . The method according to claim 1 ,
wherein the immune checkpoint inhibitor is an anti-PD-1 antibody or an anti-PD-L1 antibody.
5 . The method according to claim 1 ,
wherein the immune checkpoint inhibitor is one or more selected from the group consisting of nivolumab, pembrolizumab, and atezolizumab.
6 . The method according to claim 1 , comprising:
isolating the exosomes from the biological sample derived from the lung cancer patient with a mixture of magnetic particles bound to an anti-CD9 antibody, an anti-CD81 antibody, or an anti-CD63 antibody is used.