Precision medicine for gastrointestinal cancer: Recent progress and future perspective

Table 4 Current progress of biomarkers associated with diagnosis, prognosis, prediction of therapeutic response in gastrointestinal cancer (excluding liquid biopsy)

Market	Tumor type	Alteration	Clinical setting	Ref.
HER2	GC, CRC	Amplification, Overexpression	Predictive	Bang et al[118], 2010; Sartore-Bianchi et al[119], 2016
KRAS	CRC	Activating mutation within catalytic RAS domain	Predictive	Wormald et al, 2013; Febbo et al, 2011; Schmoll et al[122], 2012; Locker et al[123], 2006
NRAS,	CRC	Overexpression	Prognostic/Predictive	Hu et al[124], 2018
BRAF	CRC	Mutation	Prognostic/Therapeutic	Tie et al[54], 2011
KDR	CRC	Mutation	Predictive	Loaiza-Bonilla et al[125], 2016
VEGF-D	CRC	Overexpression	Predictive	Tabernero et al[126], 2018
AKT	GC	Activation	Predictive	Ito et al[127], 2017
PTEN	GC	Downregulation	Predictive	Kim et al, 2017
NTRK fusion	CRC	Overexpression	Predictive	Drilon et al[129], 2018
ALK	CRC	Rearrangement	Prognostic	Pietrantonio et al[57], 2017
POLE	CRC	Mutation	Predictive	Domingo et al[130], 2016
MMR	GC, CRC		Predictive	Llosa et al[131], 2015
PD-L1	CRC	Mutatoin	Prognostic	Eriksen et al[132], 2019
Tumor infiltrating lymphocyte	GC, CRC	Overexpression	Prognostic	Iseki et al[133], 2018
CagA	GC	Upregulated	Diagnostic	Saju et al[134], 2016
Gastrokine 1	GC	Downregulated	Diagnostic	Altieri et al[135], 2017
MEK	CRC	Activation	Predictive	Martinelli et al[136], 2017
PIK3CA	CRC	Mutation	Prognostic/ Therapeutic	Jehan et al[137], 2019; Schmoll et al[122], 2012
TP53	EC, GC, CRC	Mutation	Prognostic	Schmoll et al[122], Guo et al[138], 2017
CTNNB1	CRC EC, GC	Mutation Overexpression	Prognostic Prognostic	Gao et al[116], 2019; Szász et al[139], 2016; Ishiguro et al[140], 2016
APC	CRC	Mutation	Prognostic	Liang et al[141], 2017; Chen et al[142], 2013
IGFR-!R	CRC	Upregulation	Prognostic	Codony-Servat et al[143], 2017
SFRP2	CRC	Hypermethylation	Diagnostic/Prognostic	Tang et al, 2011
UGT1A1	CRC	Hypermethylation	Predictive	Crea et al[145], 2011
SMAD4,	EC, GC, CRC	Downregulation	Prognostic/Predictive	Salem et al[146], 2018; Wasserman et al[147], 2019
MET	EC, GC	Amplificatoin	Predictive	Van Cutsem et al[55], 2018
CDKN2A	EC,	Methylation	Diagnostic	Zhou et al, 2017
ATM	GC, CRC	Mutaion/Downregulation	Prognostic	Randon et al[149], 2019; Han et al[83], 2017
BLM,	CRC	Mutaion/Polymorphisms	Diagnostic	de Voer et al[150], 2015; Frank et al[151], 2010
BRCA1/2,	CRC	Mutaion	Diagnostic	Oh et al[152], 2018
ARID1A	GC	Mutation	Predictive	Wei et al[153], 2014
	CRC	Overexpresion	Prognostic	Ronchetti et al[154], 2017
CDH1	GC	Mutation	Diagnostic	Hansford et al[155], 2015
	CRC	Polymorphism	Diagnostic	Grünhage et al[156], 2008
CCNE1	GC	Amplification	Therapeutic	Ooi et al[157], 2017
RHOA	GC, CRC	Overexpression	Prognostic	Chang et al[158], 2016
CCND1	EC	Amplification/Overexpression	Diagnostic	Hu et al[159], 2016
	CRC	Polymorphism	Diagnostic	Grünhage et al[156], 2008
FBXW7	CRC	Mutation	Prognostic	Korphaisarn et al[160], 2017
NOTCH1	EC	Mutation	Prognostic	Song et al[161], 2016
	CRC	Gene copy number	Prognostic	Arcaroli et al[162], 2016
NOTCH3	CRC	Overexpression	Predictive	Ozawa et al[163], 2014
YAP1	EC, GC, CRC	Overexpression	Prognostic	Zhang et al[164], 2018

EC: Esophageal cancer; GC: Gastric cancer; CRC: Colorectal cancer; MMR: mismatch repair; PD-L1: programmed death ligand 1; PD-1: programmed death-1; POLE: DNA polymerase 1; HER2: human epidermal growth factor receptor type2; EGFR: epidermal growth factor receptor.