Implication of KDR Polymorphism rs2071559 on Therapeutic Outcomes and Safety of Postoperative Patients with Gastric Cancer Who Received S-1-Based Adjuvant Chemotherapy: A Real-World Exploratory Study

Figures & data

Figure 1 Flow chart of this retrospective study regarding the implication of KDR polymorphism on the prognosis of patients with gastric cancer who received S-1-based adjuvant chemotherapy.

Table 1 Baseline Characteristics of the 169 Patients with Gastric Cancer According to Genotype Status of KDR rs2071559

Baseline Characteristics	Total (N=169, %)	Rs2071559 Genotype Status		χ^2	P
		AA (N=104)	AG/GG (N=65)
Age (year)
Median (range)	56 (21–79)	56 (21–76)	56 (23–79)	NA	0.606
Gender
Male	120 (71.0)	73 (70.2)	47 (72.3)	0.087	0.768
Female	49 (29.0)	31 (29.8)	18 (27.7)
ECOG PS score
0	112 (66.3)	71 (68.3)	41 (63.1)	0.482	0.487
1–2	57 (33.7)	33 (31.7)	24 (36.9)
Pathological staging
IIA-IIB	64 (37.9)	39 (37.5)	25 (38.5)	0.016	0.900
IIIA-IIIC	105 (62.1)	65 (62.5)	40 (61.5)
Resection type
Total resection	94 (55.6)	60 (57.7)	34 (52.3)	0.470	0.493
Distal resection	75 (44.4)	44 (42.3)	31 (47.7)
Type of lymph-node dissection
D2	91 (53.8)	55 (52.9)	36 (55.4)	0.101	0.751
Non-D2	78 (46.2)	49 (47.1)	29 (44.6)
Body surface area (m^2)
Median	1.66	1.65	1.67	NA	0.513
Range	1.25–2.17	1.28–2.15	1.25–2.17
Adjuvant chemotherapy regimens
S-1 monotherapy	57 (33.7)	33 (31.7)	24 (36.9)	0.482	0.487
S-1 plus oxaliplatin	112 (66.3)	71 (68.3)	41 (63.1)
Time to initiation of adjuvant chemotherapy after surgery (year)
Median	0.95	0.93	0.95	NA	0.532
Range	0.62–1.56	0.62–1.49	0.68–1.56

Table 2 The Preliminary Analysis Between Genotype Status of the Three Polymorphisms and Disease-Free Survival

Polymorphisms	Location	MAF	Median DFS (Year)	P
rs2071559	Upstream region	0.22	6.0 vs 4.0 (AA vs AG/GG)	0.002
rs2305948	Coding region	0.15	5.4 vs 4.9 (CC vs CT/TT)	0.318
rs11941492	Intron region	0.28	5.1 vs 5.0 (CC vs CT/TT)	0.783

Figure 2 Disease free survival and overall survival of the 169 patients with gastric cancer who received S-1-based adjuvant chemotherapy.

Figure 3 Disease free survival of the 169 patients with gastric cancer who received S-1-based adjuvant chemotherapy according to KDR rs2071559 genotype status.

Figure 4 Overall survival of the 169 patients with gastric cancer who received S-1-based adjuvant chemotherapy according to KDR rs2071559 genotype status.

Table 3 Univariate and Multivariate Analyses of DFS Among the 169 Patients with Gastric Cancer

Baseline Characteristics	Median DFS (95% CI)	P (Univariate Analysis)	Multivariate Analysis
			HR (95% CI)	P
Age
<56	5.1 (4.32–5.88)	0.635
≥56	5.0 (4.07–5.93)
Gender
Female	5.5 (4.49–6.51)	0.418
Male	5.0 (4.17–5.83)
ECOG performance status score
0	6.1 (5.22–6.98)	0.008	0.69 (0.46–0.89)	0.011
1–2	4.4 (3.65–5.15)
Pathological staging
IIA-IIB	6.3 (5.49–7.11)	0.001	0.59 (0.33–0.83)	0.007
IIIA-IIIC	4.2 (3.42–4.98)
Resection type
Total resection	4.4 (3.39–5.41)	0.019	1.22 (1.09–1.67)	0.023
Distal resection	5.5 (4.66–6.34)
Type of lymph-node dissection
D2	5.5 (4.71–6.29)	0.219
Non-D2	4.9 (4.22–5.58)
Adjuvant chemotherapy regimen
S-1 monotherapy	4.9 (4.09–5.71)	0.328
S-1 plus oxaliplatin	5.4 (4.63–6.17)
KDR rs2071559 genotype status
AA	6.0 (4.61–7.39)	0.002	0.67 (0.41–0.87)	0.009
AG/GG	4.0 (3.31–4.69)
Time to initiation of adjuvant chemotherapy
After surgery (year)
≤0.95	5.3 (4.09–6.51)	0.440
>0.95	4.6 (3.52–5.68)

Figure 5 The relative expression level of KDR mRNA according to KDR rs2071559 genotype status.

Figure 6 Disease free survival of the 76 patients with gastric cancer who received S-1-based adjuvant chemotherapy according to KDR mRNA expression status.