Cytokines Association with Clinical and Pathological Changes in Esophageal Squamous Cell Carcinoma

Table 1

Prognostic values of cytokines and growth factors in ESCC.

Cytokine	Studies [reference]	Number of patients (pTNM)	Methods of detection	Protein level (% of positive)	Relationship between pTNM parameters and MVD	Survival analysis; Univariate/multivariate	Correlation with other factors
VEGF-A	Koide et al., 1999 [17]	52 (I–III)	IHC	+ (58%)	MVD+, N+, M+	𝑃<0.05/—	—
	Shih et al., 2000 [18]	117 (I–III)	IHC	+ (31%)	T+, N+, MVD+	𝑃=0.006/𝑃=0.046	—
	Mukherjee et al., 2003 [19]	55 (I–III)	IHC	+ (69%)	N+	NS	—
	Matsuyama et al., 2005 [20]	215 (I–III)	IHC	+ (53%)	—	—	HIF-1𝛼
	Choi et al., 2006 [21]	51 (I–III)	IHC	+ (41%)	NS	𝑃=0.06/𝑃=0.007	—
	Luo et al., 2011 [22]	134 (III)	IHC	+ (44%)	—	𝑃=0.003/—	—
	Kleespies et al., 2004 [23]; Kleespies et al., 2005 [54]	Review	IHC, ELISA	+; +	TNM+, T+, N+, M+, MVD+	𝑃=0.007/𝑃=0.198; 𝑃<0.001/𝑃=0.001	—; —
	Ren et al., 2005 [24]	72 (II–IV)	IHC, ELISA	+; +	—; —	—; —	MIF; MIF
	Shimada et al., 2001 [55]	96 (I–IV)	ELISA	+	TNM+, T+, N+, M+	𝑃<0.001/𝑃<0.001	—
	Ren et al., 2005 [41]	149 (I–IV)	ELISA	+	—	—	HGF
	Krzystek-Korpacka et al., 2007 [56]	25 (II–IV)	ELISA	+	T+	—	—
VEGF-C	Kitadai et al., 2001 [25]	60 (I–III)	IHC	+	TNM+, T+, N+, M+, MVD+	—	—
	Noguchi et al., 2002 [26]	71 (I–III)	IHC	+	NS	—	—
	Kimura et al., 2003 [27]	112 (I–III)	IHC	+ (39%)	TNM+, T+, N+	—	—
	Byeon et al., 2004 [28]	34 (I–III)	IHC	+ (77%)	TNM+, T+, N+	—	COX-2
	Katsuta et al., 2005 [29]	48 (I–III)	IHC	+ (60%)	NS	NS	HIF-1𝛼
	Matsumoto et al., 2006 [30]	87 (I–III)	IHC	+	T+, L+, MVD+	—	—
	Han et al., 2007 [31]	40 (I–III)	IHC	+ (60%)	NS	—	—
	Tao et al., 2012 [32]	90 (I–III)	IHC	+ (83%)	TNM+, T+, N+	—/𝑃<0.001	MMP-1
	Song et al., 2012 [33]	99 (I–III)	IHC	+ (50%)	—	—	—
	Zhang et al., 2012 [34]	49 (I–III)	IHC	+ (73%)	N+	—	—
	Zhang et al., 2012 [35]	48 (I–III)	IHC; ELISA	+; +	TNM+, T+, N+, M+; TNM+, N+, M+	𝑃<0.05/—; 𝑃<0.05/—	—
	Krzystek-Korpacka et al., 2007 [57]	70 (II–IV)	ELISA	+	N+	—	Midkine
	Krzystek-Korpacka et al., 2007 [56]	25 (II–IV)	ELISA	+	T+	—	—
	Kimura et al., 2008 [58]	80 (I–III)	ELISA	+	N+	𝑃=0.0183/𝑃=0.0069	—
	Kozlowski et al., 2010 [59]	110 (I–IV)	ELISA	+	TNM+, T+, N+, M+	𝑃=0.001/NS	—
VEGF-D	Tzao et al., 2008 [36]	85 (I–III)	IHC	+ (66%)	T+, N+	𝑃=0.001/𝑃=0.035	—
	Kozlowski et al., 2010 [59]	110 (I–IV)	ELISA	+	TNM+, T+, N+	𝑃=0.08/NS	—
TGF-𝛽	Fukai et al., 2003 [37]	80 (I–III)	IHC, ELISA	+ (36%); +	T+; NS	NS/NS	—
	Diakowska et al., 2011 [60]	115 (I–IV)	ELISA	+	T+	—	VEGF-A
IL-1𝛽	Chen et al., 2012 [38]	147 (I–III)	IHC, WB	+	TNM+	𝑃<0.0000/𝑃=0.0003	NF-𝜅B
IL-2	Mahmoodi et al., 2008 [66]	40 (I–III)	ELISA	−	—	—	—
IL-6	Oka et al., 1996 [39]	50 (I–IV)	IHC, ELISA	+ (54%)	T+	—	CRP, albumin,
	Fujiwara et al., 2011 [40]	16 (III–IV)	IHC	+	T+	—	CRP
IL-8	Ren et al., 2005 [41]	149 (I–IV)	ELISA	+	—	—	HGF, VEGF
	Ren et al., 2005 [24]	72(II–IV)	ELISA	+	—	—	—
	Krzystek-Korpacka et al., 2008 [61]	70 (I–IV)	ELISA	+	N+, M+	—	VEGF-C
IL-12	Diakowska et al., 2006 [62]	41 (I–IV)	ELISA	+	TNM+	—	IL-18
IL-18	Diakowska et al., 2006 [62]	41 (I–IV)	ELISA	+	TNM+, T+, N+	—	IL-12
PDGF-BB	Krzystek-Korpacka et al., 2011 [63]	84 (II–IV)	ELISA	+ (76%)	TNM+, N+, M+	—	VEGF-A, VEGF-C
HGF	Ren et al., 2005 [41]	149 (I–IV)	ELISA, IHC, WB	+	TNM+, M+	𝑃=0.0137/𝑃=0.0001	VEGF, IL-8
	Takada et al., 1995 [64]	37 (I–III)	ELISA	+ (97%)	NS	NS	—
CTGF	Zhou et al., 2009 [42]	80 (I–III)	IHC, WB	+ (49%)	NS	𝑃=0.018/𝑃=0.028	Thrombospondin (THBSI), cysteine-rich protein 6I (Cyr6I)
CXCL12	Sasaki et al., 2009 [43]	214 (I–IV)	IHC	+(54%	TNM+, N+	𝑃=0.006/𝑃=0.262	—
FasL	Shibakita et al., 1999 [44]	106 (I–III)	IHC	+ (49%)	LV+	NS/NS	—
	Takikita et al., 2010 [45]	313 (I–III)	IHC	+ (4%)	NS	𝑃=0.45/NS	—
	Kozlowski et al., 2007 [65]	100 (I–IV)	ELISA	+	TNM+, N+, M+	𝑃=0.52/NS	—
aFGF	Sugiura et al., 2007 [46]	79 (I–III)	IHC	+ (59%)	NS	𝑃=0.06/NS	bFGF, FGF-R
bFGF	Han et al., 2005 [47]	79 (I–IV)	IHC	+ (72%)	TNM+, T+, N+, MVD+	𝑃=0.021/—	HPS
IFN-𝛾	Mahmoodi et al., 2008 [66]	40 (I–III)	ELISA	−	—	—	—
IGFBP7	Kashyap et al., 2013 [48]	140 (I–III)	IHC	+ (91%)	—	—	—
IGF-II	Imsumran et al., 2007 [49]	100 (I–III)	IHC	+ (50%)	TNM+, T+, N+, M+	𝑃=0.0028/𝑃=0.0027	—
Midkine; (HBGF)	Ren et al., 2006 [50]	66 (I–III)	IHC	+ (56%)	NS	NS	—
	Shimada et al., 2003 [51]	93 (I–IV); 14 (I–III)	ELISA, IHC	+; + (61%)	NS; NS	𝑃<0.001/𝑃=0.004	—
	Krzystek-Korpacka et al., 2007 [57]	70 (II–IV)	ELISA	+	TNM+, T+, N+, M+	—	VEGF-C
MIF	Ren et al., 2005 [24]	72 (II–IV)	IHC; ELISA	+; +	N+, MVD+	𝑃=0.03/NS	VEGF; VEGF, IL-8
	Xia et al., 2005 [52]	52 (I–III)	WB	+ (96%)	—	—	—
	Zhang et al., 2013 [53]	136 (I–III)	IHC	+	NS	𝑃<0.033/𝑃<0.011	CXCR4

IHC: immunohistochemistry, ELISA: enzyme-linked immunosorbent assay, WB: western blot, pTNM: pathological TNM staging system, +: overexpression, −: lower level versus control, NS: not statistically significant, TNM+: progression of cancer stage, T+: tumor progression, N+: lymph node metastasis, M+: distant metastasis, MVD+: microvessel density progression, LV+: lymph vessel invasion, —: not tested, HIF-1𝛼: hypoxia inducible factor-1 alpha, NF-𝜅B: nuclear factor-kappa B, HPS: heparinase, CRP: C-reactive protein, and COX-2: cyclooxygenase-2; other names are in Abbreviations.