Table 3.

Putative predictive markers of the patient’s response to bevacizumab/erlotinib

Time	Endpointa	Gene symbols	KEGG pathway enrichment
Baseline	TS12	ANO2, VPS13D, EML1, C22orf31, FERMT1, SFRP4, SUPT6H, GYS2, THBS4, ATP6V1B1, TCF21, ESRRB, NEUROD4, SOX15, GATA5, PRRC2B, SLC7A10, LOXL4, DISP2, TRIM7, DRD2, GPHA2, KCTD15, PAQR4, ANKZF1, SHROOM1, FABP7, FBXL21, KCNK5, MBL2, LY6D, VASN, FSTL5, MECP2, ROR2, TPT1-AS1, DCDC1, HS6ST2, HSPB7, NWD2, OR5M3, SLC35E3, UNC119B, OR10AB1P, UMODL1, ERN1, RNF151, CALHM1, TMPRSS12, KLK12, KRT14, LINC01551, NWD1, C15orf52, IL1RAPL2, TRRAP, TPK1, MYO18A, DSCR8, B3GNT6, RNA5SP430, C1orf132, PPAPDC1A, BTBD17, LAYN, CST9LP1, ST8SIA6-AS1, AL592528.1, RP11-337C18.4, GAPDHP44, HAUS7, AC010904.1, CELA3B, RP1-288M22.1, U3, CTA-929C8.7, ARSEP1, UBE2D3P4, RP11-38C18.2, RP11-94M14.2, AC007312.3, LINC00237, RP11-66N5.2, LINC01375, C1DP4, RP11-20P5.2, RP5-888M10.2, AC105443.2, FGFR1OP2P1, RP5-855F14.2, TFAMP1, POLR3KP1, CRYGFP, TBC1D3P7, RP11-336N8.1, DCUN1D2-AS, RP11-528G1.2, ZBTB22, TSPY15P, RP11-98G13.1, AC007679.4, KCNQ1DN, RN7SL549P, SMKR1, PNMA2, PI4KA, RP11-520P18.1, RP11-572M11.3, OR10J7P, RP11-331K21.1, RP11-340A13.1, LINC00977, RP3-368B9.2, SNORA18, HNRNPCP8, MPV17L2, NAV2-AS5, CTD-2517M22.14, ENPP7P5, RP11-150C16.1, HNRNPA3P10, RP11-316E14.2, RP11-566K19.5, RP11-521O16.1, RP11-616M22.7, RP11-523L20.2, AC009120.4, RP11-106M3.3, RP11-553K8.5, RP11-189E14.4, RP11-520P18.5, SAMD11P1, RP11-286N3.2, SNRPCP4, RP11-343K8.3, AC005307.3, AC010524.4, CTB-31C7.3, WI2-80269A6.1, RP11-401N16.1, RP11-416H1.1, RP11-1072C15.7	Phagosome (hsa04145, $p=0.052$) Protein digestion and absorption (hsa04974, $p=0.058$)
	DS12	–	–
	OS	CASC1, HIST1H1A, FAM86C2P, Y_RNA, IGHV5-51, RP11-174G6.1, HNRNPA1P63, EEF1B2P1, RP3-403L10.3, RPL7P53, IGKV1-5, MRPS36P2, RP11-415I12.3, RNU6-412P, RNU6-1224P, RP11-61G23.2, CTD-2547H18.1, RP11-295G12.1, ZNF23	–
	TTPBE	BDKRB1, NRN1, LAMC1, ZNF462, LRRC43, SGSM1, FSCN2, C9orf92, RNU6-83P, RPL7AP14, RP11-793K1.1, RP3-433F14.1, RP1-292B18.4, AC098592.7, AC114812.8, TOMM20P1, LL22NC03-88E1.17, C12orf77, RP1-213J1P__B.1, LINC01038, MARK2P12, XRCC6P3, SHC1P1, RP3-463P15.1, LL0XNC01-116E7.2, COL4A2-AS1, CYCSP44, RAC1P8, SLMO2-ATP5E, AF127577.12, STARD13-AS, RN7SL797P, RN7SL598P, RP11-544A12.8, RP11-415I12.3, RP11-61G23.2, RP11-6B19.3, RP11-136F16.2, CASC18, AC002306.1, RP11-552E10.1, RP11-361M10.3, RP11-203B7.2, RP11-475B2.1, RP11-763E3.1, RP13-516M14.2, RP11-820I16.1	–
	TTPCT	KRTAP2-3, AC090957.2, KALP, RP11-157I4.4, TSIX	–
24h after initiation of BE	TS12	PDZD4, SH3BP1, CALD1, SPX, MAPKBP1, MMRN1, EGF, PLOD2, ANKRD61, FZD5, CLEC1B, SLC39A13, SMCO4, BCRP2, TSNARE1, TDRP, TOP1MT, TPTE2P3, RNU105C, Y_RNA, RN7SKP257, AC006988.1, ATP5HP3, RNU6-887P, RP11-361F15.2, BANF1P2, AC099344.2, LINC00884, DDX39BP2, RP11-486M23.1, RP11-167N24.3, RP11-693J15.3, RP11-433P17.3	Pathways in cancer (hsa05200, $p=0.031$)
	DS12	–	–
	OS	MYO1C, Y_RNA, DEFB134, Y_RNA, IGLV3-21, IGLC7, IGHA2, IGHA1, IGHV3-15, IGHV3-23, IGHV5-51, SOD1P1, AC016768.1, LINC01032, ZSCAN31, RP11-169N13.4, IGKV1-5, IGHV3-65, IGLC4, RP11-280K24.1	–
	TTPBE	TNMD, TSPAN9, PRICKLE3, RAD51, MCM10, TCF3, ATP2A3, OPHN1, FBXL19, PCK2, PLTP, E2F1, PCYT1B, CKM, APBA1, CNTNAP1, FOXM1, KIF20A, CIT, HJURP, E2F8, KLF16, APOC1, ATP8B3, EPHB2, CTIF, TICRR, CTU1, CPXCR1, GRIK4, C16orf78, CKB, VKORC1, TK1, METTL7B, MZB1, ZNF296, RRM2, JUP, PCP2, CADM2, SLC25A22, KLHL28, GJC1, MARCH11, GAS2L1, MITF, HIST1H2BM, SLC25A29, SRC, MYO1C, RNU12-2P, Y_RNA, D86998.1, IGLV6-57, IGLV3-21, IGHG1, IGHJ1, IGHV6-1, IGHV4-28, AP005482.3, RP3-407E4.4, RP11-535M15.1, IPPKP1, FAM195B, RP11-69C17.2, HDGFP1, SCAMP4, RD3L, TUBB4AP1, SDAD1P2, RP11-321L2.1, SPATA31B1P, AC005772.2, RP11-22C8.1, VN1R38P, ITGA9-AS1, NIFK-AS1, B3GNT9, RP11-252M21.6, RN7SL60P, RP11-266N13.2, RP11-517I3.1, RP11-364C11.2, RACGAP1P, RP11-545N8.3, RP11-81A1.3, RP11-2C24.5, AF213884.2, PRKCA-AS1, CTD-2319I12.2	Melanoma (hsa05218, $p=0.029$) Pancreatic cancer (hsa05212, $p=0.029$) PPAR signaling cancer (hsa03320, $p=0.029$) arginine and proline metabolism (hsa00330, $p=0.029$) Pathways in cancer (hsa05200, $p=0.029$) Pyrimidine metabolism (hsa00240, $p=0.041$)
	TTPCT	TTTY14, MTND1P4, RP11-875H7.2, LINC01021, AC008565.1, LINC01486	–

Gene significantly predictive of the patient’s response ($p<0.001$) are reported together with the associated enriched KEGG pathways. Genes that belonged to the KEGG pathway “Pathways in cancer” are highlighted in italic

^aTS12: tumor shrinkage at 12 weeks; DS12: disease stabilization at 12 weeks; OS: overall survival; TTPBE: time-to-progression under bevacizumab/erlotinib; TTPCT: time-to-progression under chemotherapy