Supplement

sTable1. The information of platforms in this article

No. of early- Datasets Platform stage LUSC Derivation TCGA LUSC RNA-seqV2 385

GSE37745 Affymetrix U133 Plus 2.0 Array 54 Validation GSE41271 Illumina HumanWG-6 v3.0 expression beadchip 47

sTable2. The full names and LASSO coefficients of 68 IRGPs

IRG1 Full Name IRG2 Full Name Lasso Coefficient corticotropin releasing hormone CRHR2 PTGER1 prostaglandin E 1 0.207083825 receptor 2 GCGR glucagon receptor PPBP pro-platelet basic protein 0.02004656 killer cell immunoglobulin like oxytocin/neurophysin I KIR2DL3 receptor, two Ig domains and OXT 0.121315514 prepropeptide long cytoplasmic tail 3 IL1RL2 interleukin 1 receptor like 2 SEMA6B semaphorin 6B 0.005241907 AMH anti-Mullerian hormone TNFRSF8 TNF receptor superfamily 0.006682232 ANGPTL7 angiopoietin like 7 OXT oxytocin/neurophysin I 0.199735351 CBLC Cbl proto-oncogene C CD14 CD14 molecule 0.137431449 vav guanine nucleotide CRLF3 cytokine receptor like factor 3 VAV2 0.016581293 exchange factor 2 GPR17 G protein-coupled receptor 17 LBP lipopolysaccharide binding 0.267159854 GZMB granzyme B TRIM22 tripartite motif containing 22 0.053449123 major histocompatibility tubulointerstitial nephritis HLA-DOA TINAGL1 0.255045783 complex, class II, DO alpha antigen like 1 IL10 interleukin 10 PTX3 pentraxin 3 0.189325253 IL19 interleukin 19 PROK2 prokineticin 2 0.042237596 KLKB1 kallikrein B1 PROK2 prokineticin 2 0.161555622 platelet derived growth factor TNF receptor superfamily PDGFRL TNFRSF10A 0.620931083 receptor like member 10a APLNR apelin receptor IL1B interleukin 1 beta 0.105011265 BDNF brain derived neurotrophic RBP4 retinol binding protein 4 0.010130904 CRLF2 cytokine receptor like factor 2 PPBP pro-platelet basic protein 0.006366025 C-X-C motif chemokine CXCR5 ELANE elastase, neutrophil expressed 0.005360128 receptor 5 FGF8 fibroblast growth factor 8 HTR3A 5-hydroxytryptamine receptor 0.147815561 GALR3 3 PYY peptide YY 0.176134308 IFNA21 interferon alpha 21 TRH thyrotropin releasing hormone 0.039480337 IFNW1 interferon omega 1 TRH thyrotropin releasing hormone 0.045793487 interleukin 2 receptor subunit platelet activating factor IL2RB PTAFR 0.003972825 beta receptor killer cell immunoglobulin like KIR3DL1 receptor, three Ig domains and VIP vasoactive intestinal peptide 0.305407995 long cytoplasmic tail 1 PENK proenkephalin PLA2G2A phospholipase A2 group IIA 0.06071904 ANGPTL3 angiopoietin like 3 MSTN myostatin 0.029097514 BMP3 bone morphogenetic protein 3 FABP6 fatty acid binding protein 6 0.010145812 radical S-adenosyl methionine BMP4 bone morphogenetic protein 4 RSAD2 0.075844877 domain containing 2 calcitonin related polypeptide CALCB NPPA natriuretic peptide A 0.02356709 beta CALCR CMA1 chymase 1 0.182197326 gremlin 1, DAN family BMP CCL22 C-C motif chemokine ligand 22 GREM1 0.482701349 antagonist CCR8 C-C motif chemokine receptor 8 PLA2G2A phospholipase A2 group IIA 0.060649853 C-X-C motif chemokine vascular endothelial growth CXCR6 VEGFC 0.189414791 receptor 6 factor C DCK deoxycytidine kinase SYK spleen associated tyrosine 0.008181958 hepatocyte nuclear factor 4 FGF5 fibroblast growth factor 5 HNF4A 0.218363453 alpha nuclear receptor subfamily 4 INHBB inhibin subunit beta B NR4A1 0.008053992 group A member 1 NPR3 natriuretic peptide receptor 3 RBP7 retinol binding protein 7 0.048361377 RORB RAR related orphan receptor B SSTR1 1 0.074187311 CKLF like MARVEL latent transforming growth CMTM3 transmembrane domain LTBP1 -0.121456795 factor beta binding protein 1 containing 3 SLC40A1 solute carrier family 40 member TNC tenascin C -0.149124697 ARRB1 arrestin beta 1 GNLY granulysin -0.018611232 CCL16 C-C motif chemokine ligand 16 IL19 interleukin 19 -0.008156399 FABP6 fatty acid binding protein 6 PLXNA2 plexin A2 -0.200983247 ANGPTL1 angiopoietin like 1 HAMP hepcidin antimicrobial peptide -0.13730128 CCL1 C-C motif chemokine ligand 1 CST4 cystatin S -0.094059881 MPL proto-oncogene, LEFTY2 left-right determination factor 2 MPL -0.071549963 thrombopoietin receptor TNF receptor superfamily CD70 CD70 molecule TNFRSF9 -0.052229093 member 9 IL1B interleukin 1 beta TGFB3 transforming growth factor beta -0.050552888 nucleotide binding NOD2 oligomerization domain PLCG2 phospholipase C gamma 2 -0.07386481 containing 2 PTGER1 prostaglandin E receptor 1 TNFSF11 TNF superfamily member 11 -0.117341735 AREG amphiregulin TAPBPL TAP binding protein like -0.051566923 nuclear receptor subfamily 2 BMP2 bone morphogenetic protein 2 NR2F2 -0.060282876 group F member 2 FGA fibrinogen alpha chain ORM2 orosomucoid 2 -0.20152686 fibroblast growth factor leucine rich repeat containing G FGFRL1 LGR4 -0.093206023 receptor like 1 protein-coupled receptor 4 nuclear receptor subfamily 4 NR4A2 ROBO1 roundabout guidance receptor 1 -0.052711638 group A member 2 platelet derived growth factor phosphoinositide-3-kinase PDGFRA PIK3R1 -0.033476768 receptor alpha regulatory subunit 1 major histocompatibility BMP2 bone morphogenetic protein 2 MR1 -0.021856305 complex, class I-related nucleotide binding nuclear receptor subfamily 2 NOD1 oligomerization domain NR2C1 -0.004717251 group C member 1 containing 1 interleukin 3 receptor subunit SOS Ras/Rho guanine IL3RA SOS2 -0.10914976 alpha nucleotide exchange factor 2 nuclear receptor subfamily 1 CCR1 C-C motif chemokine receptor 1 NR1H3 -0.053056659 group H member 3 INSL3 insulin like 3 NPPC natriuretic peptide C -0.136713953 MPL proto-oncogene, APOH apolipoprotein H MPL -0.004715036 thrombopoietin receptor VDR vitamin D receptor WNT5A Wnt family member 5A -0.157638544 C-type lectin domain containing CLEC11A PLCG1 phospholipase C gamma 1 -0.15794361 11A IL1A interleukin 1 alpha PGF placental growth factor -0.348533319 IRF5 interferon regulatory factor 5 WNT5A Wnt family member 5A -0.065123813 interleukin 3 receptor subunit protein phosphatase 3 catalytic IL3RA PPP3CC -0.319870145 alpha subunit gamma sFig1. ontology of the unique 123 LUSC immune-relate (IRGs)

sFig2. The optimal cutoff of IRGPI for stratifying patients based on time-dependent ROC curve analysis in the TCGA derivation cohort