Table 2.

Tumor tissue biomarkers associated with prognosis in CCA.

Name	Occurrence	Expression	Associated Prognostic Value	Reference
Cell Surface Molecules
CD 155	CCA	Increased	OS, DFS, histological grading, lymph node metastasis	[77]
CD44	Liver fluke-associated CCA	Increased	OS	[78]
CD55, CD97	iCCA	Increased	OS, histological grading, lymph node metastasis, venous invasion	[165]
CD98	CCA	Increased	OS	[166]
Signaling Molecules, Growth Pathways, Angiogenesis
IL-6	iCCA	Increased	OS, DFS	[47]
IL-17	iCCA	Increased peritumoral expression	OS, DFS	[47]
SOCS3	CCA	Low intratumoral expression	OS, lymph node metastasis, postoperative disease recurrence	[80]
Tumor necrosis factor α-induced protein 3 (TNFAIP3 or A20)	CCA	Increased intratumoral expression	OS, lymph node metastasis, postoperative disease recurrence	[80]
RNF43	iCCA	Low intratumoral expression	OS	[81]
LIM and SH3 protein 1 (LASP-1)	CCA	Increased intratumoral expression	OS, tumor size, histological differentiation, lymph node metastasis, TNM stage	[82]
B7-H4	CCA	Increased	OS, histological differentiation, lymph node metastasis, staging, early recurrence of tumor	[83]
Hepatoma-derived growth factor (HDGF)	iCCA	Increased	OS, lymph node metastasis, TNM stage	[84]
Ki-67, p73	pCCA	Increased	OS, TNM stage	[85]
Sex-determining region Y-box 4 (SOX4)	iCCA	Increased	OS	[86]
Sex-determining region Y-box 9 (SOX9)	iCCA	Increased	OS	[86]
KRAS	CCA	Increased	OS	[167]
TP53	CCA	Increased	OS	[167]
ARID1A	CCA, mostly fluke-associated iCCA	Decreased	OS	[71,72]
	iCCA	Increased	OS, recurrence rate	[73]
EGFR, MUC1, MUC4, fascin	CCA	Increased	OS	Metanalysis by [74]
VEGF, COX-2, GLUT-1, cyclin D1, Ki67	eCCA	Increased	OS	Metanalysis by [75]
p16, p27, E-cadherin	eCCA	Increased	OS	Metanalysis by [75]
c-MET	CCA	Increased	OS, DFS	[168]
DKK1	iCCA, pCCA	Increased	OS, lymph-node metastasis	[169,170]
BAP1	CCA	Retained expression	OS, DFS	[25,169,170]
		Loss of expression	Trend towards improved OS, histological differentiation, lymph-node metastasis
PBRM1	CCA	Retained expression	OS, DFS	[29,171]
Mucins
MUC5AC	Liver fluke-associated iCCA, iCCA	Increased	OS, lymph node metastasis, TNM stage, tumor size	[88,89]
MUC4	CCA	Increased	OS	[172]
MUC16	iCCA	Increased	OS	[173]
Tumor Stroma and Microenvironment
Epithelial cell adhesion molecule (EpCAM)	iCCA	Increased expression in peritumoral stroma	OS, DFS	[90]
Lysil oxidase-like 2 (LOXL2)	iCCA	Increased expression in peritumoral stroma	OS, DFS	[91]
Matrix metalloproteinase -9 (MMP-9)	pCCA	Increased tissue expression	OS	[92]
Matrix metalloproteinase -11 (MMP-11)	CCA	Increased tissue expression	OS	[93]
Non-Coding RNA
lncRNA H19	CCA	Increased tissue expression	OS, DFS, tumor size, TNM stage	[95]
lncRNA-PANDRA	CCA	Increased tissue expression	OS, DFS, lymph node metastasis, TNM stage	[96]
Panel (miR-675-5p, miR-652-3p and miR-338-3p)	iCCA	Overexpression	OS, DFS	[97]
miR-29a	CCA	Overexpression	OS, lymph node metastasis, histological differentiation, clinical staging	[98]
miR-21	Liver fluke-associated iCCA	Overexpression	OS, lymph-node metastasis	[174]
miR-92b	CCA	Overexpression	OS	[175]
miR-34a	eCCA	Decreased expression	OS, lymph-node metastasis, clinical stage	[176]
miR-181a	CCA	Overexpression	OS	[177]
miR-191	iCCA	Overexpression	OS, DFS	[178]
miR-203, miR-373	CCA	Decreased expression	OS, DFS	[178,179]
miR-221	eCCA	Overexpression	DFS	[180]