A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients

Figures & data

Table 1. Patient, tumor and treatment characteristics of the patients included in the study

	Sample set
Characteristic	No.	%
Age	Median (range) yrs	60 (20–77)
Sex	Male	24	57
	Female	18	43
Tumor distance from the anal verge	≤ 7 cm	23	55
	> 7 cm	19	45
Total radiotherapy dose delivered	≥ 50 Gy	38	90
	< 50 Gy	4	10
5-Fluorouracil administration	Continuous infusion	33	79
	Bolus	8	19
	Oral (capecitabine)	1	2
Other drugs	5-Fluorouracile alone	27	64
	Oxaliplatin	11	26
	Carboplatin	4	10
ypTNM	0	6	14
	I	13	31
	II	13	31
	III	4	10
	IV	6	14
	Not available	0	0
Radical surgery	Yes	34	81
	No	8	19
	Not available	0	0
Pre-chemotherapeutic CEA (ng ml^−1)	<5/ ≥5	30/ 7	71/17
	Not available	5	12

5-FU= 5-Fluorouracil; CEA= carcinoembryonic antigen

Table 2: List of 19 informative genes (adjusted p-value = 0.037) discriminating responders and non-responders groups

Gene Symbol	AffyID	Chromosome	Description
AGRN	217419_x_at	chr1	agrin
HFM1	241469_at	chr1	ATP-dependent DNA helicase homolog (S. cerevisiae)
CSTF3	203947_at	chr11	cleavage stimulation factor subunit 3 isoform 1
RAB6A	221792_at	chr11	RAB6A, member RAS oncogene family isoform a
PRKRIR	209323_at	chr11	protein-kinase, interferon-inducible double
C12orf32	225837_at	chr12	chromosome 12 open reading frame 32
XRCC3	216299_s_at	chr14	X-ray repair cross complementing protein 3
CDK10	203468_at	chr16	cyclin-dependent kinase 10 isoform b
CDK5R1	204996_s_at	chr17	cyclin-dependent kinase 5, regulatory subunit 1
IL12RB1	1552584_at	chr19	interleukin 12 receptor, β 1 isoform 1
BCKDHA	239158_at	chr19	branched chain keto acid dehydrogenase E1, α
ZNF160	1567031_at	chr19	zinc finger protein 160
ASXL2	231417_at	chr2	additional sex combs like 2
EIF3L	217719_at	chr22	eukaryotic translation initiation factor 3
PSMD6	232284_at	chr3	proteasome (prosome, macropain) 26S subunit,
MAGI1	232859_s_at	chr3	membrane associated guanylate kinase, WW and PDZ
RAB7A	1570061_at	chr3	RAB7, member RAS oncogene family
SPRY4	220983_s_at	chr5	sprouty homolog 4 isoform 1
CNKSR2	1554607_at	chrX	connector enhancer of kinase suppressor of Ras

Figure 1. Hierarchical clustering of 42 patients with rectal carcinomas based on significantly differentially expressed probe sets representing 19 genes (rows) between the subgroup of responders and non-responders (columns) to neoadjuvant chemoradiotherapy. Responders are located on the left branch, Non-responders are clustered on the right branch. Red depicts decreased gene expression; blue indicates increased expression. The two asterisks identify the outliers.

Figure 2. Caspase activation assay on HCT116 and HCT116 p53−/− cells. (A) XRC33 knockdown does not influence caspase activation in HCT116 cells. (B) 5-FU, in combination with XRCC3 knockdown, causes a significant increase of caspase 3/7 activation as compared to control group in HCT116 p53−/− cells. Luminescence is expressed as Relative Light Units (RLU). *: p-value <0.05 compared to control group in t-test with Bonferroni's correction. Error bars represent standard errors of the mean.

Figure 3. NAViGaTOR PPI network for the 3 of the 4 predictor genes (rectangle nodes).

Figure 4. microRNAs targeting the predictor genes PPI network. White squares: microRNAs shared by the 3 genes; pink squares: signature microRNAs described in the literature. The size of the microRNA node corresponds to number of target genes it has. Thick blue lines highlight direct links between predictor genes and corresponding microRNAs.

Figure 5. Drugs targeting the predictor genes PPI network. The size of the node corresponds to number of proteins it targets.