Integration of genome scale data for identifying new players in colorectal cancer

Table 1 Relevant studies that integrated copy number variations and gene expression data when studying colorectal cancer

Ref.	Case series		Chr 20q (gain)	Chr 8p (loss)	Additional genes/chromosomes
	CNV	mRNA
Ali Hassan et al[24]	64 couples (4 A, 33 B, 27 C1)	15/64 couples	20q12	8p23.2	Gains: 8q21-22, 8q24, 13q21, 13q34, 20p11-13, 20q11-13
			PTPRT2	CSMD1
			CHD6	DLC1
			EMILIN3
			LPIN3
			PLCG12
			TOP12
			ZHX3
			MAFB
Loo et al[25]	40 couples	40 couples	20q11-13	8p	Gains: 20pter-p12 (PCNA), 20p13 (CDC25B), 13q34 (CUL4A)
			AHCY	FBXO25
			POFUT1 RPN2	MTUS12
			TH1L	EPHX2
			PRPF6	KIF13B
			AURKA	PPP2CB2
Yoshida et al[26]	70 couples	70 couples			Gains: 1q21 (S1000A2), 18p11 (RALBP1, TYMS, RAB12, RNMT), 15q26 (ABHD2), 20p11 (ABHD12)
					Losses: 3q29 (LOC440995), 4q13 (UGT2B28, SULT1B1), 4q21 (CXCL6, CXCL3), 10q22 (OIT3), 12p12 (ARHGDIB)
Kikuchi et al[27]	122 couples (18 I, 42 II, 37 III, 25 IV3)	115/122 couples (16 I, 41 II, 35 III, 23 IV3)			Gains: 1q32.1 (NUCKS1), 1q42 (TMEM63A), 3p14.2 (SYNPR)
Reid et al[18]	48 couples (1 I, 10 II, 10 III, 23 IV3, 4 N.I.)	36/48 couples (1 I, 5 II, 8 III, 19 IV3, 4 N.I.)	20q11-13		Gains: 7p12 (EGFR), 8q24 (NDRG1), 13q (TFDP1, CDK8, GAS6, SPATA13)
			PLCG1	8p21-24
			ADRM1	BIN	Losses: 6p21, 8p, 18q (MAPRE2, INO80C, ARKL1), 20p (FKBP12)
			JAG1	DBC1
			AURKA	TNFRSF10A
			C20ORF20	TNFRSF10B
			C20ORF24 TCFL5	EXTL3
			TH1L
			AHCY
			TGIF2

¹Duke’s;

²CRC-related;

³Stage. Chr: Chromosome; CNV: Copy number variations; CRC: Colorectal cancer; Couple: Tumor tissue matched with its normal colorectal mucosa. Genes identified in more than one study are shown in bold font.

Table 2 Studies that integrated gene and miRNA expression data when studying colorectal cancer

Ref.	Case series		Modulated genes	Modulated miRNA	miRNA/mRNA pairs with opposite expression
	mRNA	miRNA			Predicted	Confirmed
Fu et al[39]	8 couples (1 I, 4 II, 3 III1)	8 couples (1 I, 4 II, 3 III1)	2916 N vs T	32 N vs T	72 miRNA/mRNA	mir-29a/KLF4, miR-224/SFRP2
Vishnubalaji et al[40]	13 couples (5 II, 8 III1)	13 couples (5 II, 8 III1)	3175 N vs T	103 N vs T	794 miRNA (downregulated)/mRNA	miR-26a-5p/EZH2 let-7b-5p/EZH2
Pizzini et al[41]	80 samples (23 NOR, 30 CRC, 27 liver metastasis)	78 samples (23 NOR, 31 CRC, 24 liver metastasis)	12748 N vs T	N vs T	3078 miRNA/mRNA	miR182/ENTPD5, miR-145/c-Myc
Lanza et al[42]	39 couples (23 MSS, 16 MSI-H)	39 couples (23 MSS, 16 MSI-H)	72 MSI-H vs MSS colon cancers	14 MSI-H vs MSS colon cancers		Predictor composed of 27 elements (genes and miRNAs) for distinguishing MSI-H vs MSS
Gattolliat et al[44]	9 NOR, 37 CRA, 9 CRC	5 NOR, 28 CRA, 15 CRC		1 CRC vs NOR, 2 CRA vs NOR, 5 CRA and CRC vs NOR		miR-21/PDCD4, miR-21/MARCKS, miR-200b/ZEB2, miR-15b/BCL2, miR-16/BCL2, miR-21/BCL2
Reid et al[45]	7 public gene expression datasets CRC vs N samples	40 couples (10 A, 10 B, 10 C, 10 D)	7629 N vs T	70 N vs T		miR-1/MET
Ling et al[47]	SW480 cells after miR-224 overexpression (84 metastasis related genes analyzed)	4 CRC with metastasis, 8 CRC without metastasis, SW480, SW620	13 metastasis-related genes down-regulated	4 up in primary metastatic CRCs vs early CRC stages	miR-224/SMAD4 miR-224/CDH1	miR-224/SMAD4

¹Stage. Couple: Tumor tissue matched with its normal colorectal mucosa; CRA: Colorectal adenoma; CRC: Colorectal cancer; NOR: Normal colorectal mucosa.

Table 3 Relevant studies that integrated methylation and gene expression profiles

Ref.	Case series		Genes
	Methylation	mRNA
Hinoue et al[56]	29 NOR, 125 CRC	19 couples	464 genes downregulated CIMP-H vs normal samples, 112 of them (24%) exhibit promoter hypermethylation
			12 genes downregulated and hypermethylated in non-CIMP tumors
Szmida et al[57]	12 couples	19 couples (from Hinoue et al[56], 2012)	4 ErbB-associated genes (PIK3CD, PKCΒ, ERBB4, PAK7) differentially methylated in CRC
Wang et al[58]	42 NOR, 231 CRC	26 NOR, 231 CRC	118 methylation-perturbed genes whose expression is affected by the highly variable DNA methylation sites

Couple: Tumor tissue matched with its normal colorectal mucosa; CRC: Colorectal cancer; NOR: Normal colorectal mucosa.