Serum Helicobacter pylori KatA and AhpC antibodies as novel biomarkers for gastric cancer

Table 1 Association between gastric cancer and seropositivity of catalase and alkyl hydroperoxide reductase antibodies in study subjects n (%)

Virulence factors serostatus	All subjects				H. pylori positive subjects				H. pylori negative subjects
	Case	Control	OR (95%CI)	P value1	Case	Control	OR (95%CI)	P value1	Case	Control	OR (95%CI)	P value1
KatA
Negative	78 (33.62)	228 (86.36)	1.0 (Reference)	< 0.001	47 (35.61)	104 (88.14)	1.0 (Reference)	< 0.001	26 (29.21)	109 (83.85)	1.0 (Reference)	< 0.001
Positive	154 (66.38)	36 (13.64)	12.84 (7.80-21.15)		85 (64.39)	14 (11.86)	14.59 (6.84-31.13)		63 (70.79)	21 (16.15)	12.15 (5.79-25.51)
AhpC
Negative	56 (24.14)	121 (45.83)	1.0 (Reference)	< 0.001	33 (25.00)	57 (48.31)	1.0 (Reference)	< 0.001	54 (54.00)	103 (70.55)	1.0 (Reference)	< 0.001
Positive	176 (75.86)	143 (54.17)	2.40 (1.55-3.73)		99 (75.00)	61 (51.69)	2.30 (1.25-4.23)		46 (46.00)	43 (29.45)	2.04 (1.10-3.78)
Combination of KatA and AhpC
Negative	78 (33.62)	226 (85.61)	1.0 (Reference)	< 0.001	49 (37.12)	104 (88.14)	1.0 (Reference)	< 0.001	33 (33.00)	127 (86.99)	1.0 (Reference)	< 0.001
Positive	154 (66.38)	38 (14.39)	11.64 (7.12-19.01)		83 (62.88)	14 (11.86)	13.40 (6.29-28.53)		67 (67.00)	19 (13.01)	13.91 (6.74-28.74)

¹The P value was obtained from logistic regression analysis adjusted for age, sex, family history of gastric cancer, smoking, and alcohol consumption. KatA: Catalase; AhpC: Alkyl hydroperoxide reductase.

Table 2 Dose-dependent association between gastric cancer risk and serum catalase and alkyl hydroperoxide antibodies levels in study subjects n (%)

All subjects					H. pylori positive subjects					H. pylori negative subjects
Antibody level (OD)1	Case	Control	OR (95%CI)2	P value for trend	Antibody level (OD)	Case	Control	OR (95%CI)2	P value for trend	Antibody level (OD)	Case	Control	OR (95%CI)2	P value for trend
KatA
≤ 0.4187	167 (71.98)	66 (25.0)	1.0 (Reference)	< 0.001	≤ 0.4152	92 (69.70)	29 (24.58)	1.0 (Reference)	< 0.001	≤ 0.4167	66 (74.16)	32 (24.58)	1.0 (Reference)	< 0.001
0.4187-0.5313	36 (15.52)	66 (25.0)	4.25 (2.49-7.27)		0.4152-0.5133	23 (17.42)	30 (25.42)	3.79 (1.78-8.06)		0.4167-0.5568	9 (10.11)	33 (25.42)	6.67 (2.70-16.51)
0.5313-0.6799	18 (7.76)	66 (25.0)	9.95 (5.05-19.62)		0.5133-0.6692	9 (6.82)	30 (25.42)	9.69 (3.81-24.70)		0.5568-0.6824	11 (21.36)	33 (25.42)	7.00 (2.68-18.30)
> 0.6799	11 (4.74)	66 (25.0)	15.85 (6.97-36.06)		> 0.6692	8 (6.06)	29 (24.58)	16.55 (5.51-49.76)		> 0.6824	3 (3.39)	32 (24.58)	19.89 (4.32-91.70)
AhpC
≤ 0.2168	88 (37.93)	66 (25.00)	1.0 (Reference)	< 0.001	≤ 0.2182	51 (38.64)	29 (24.58)	1.0 (Reference)	< 0.001	≤ 0.2110	31 (34.83)	32 (24.58)	1.0 (Reference)	< 0.001
0.2168-0.3265	69 (29.74)	66 (25.00)	1.26 (0.76-2.11)		0.2182-0.3433	41 (31.06)	30 (25.42)	1.10 (0.54-2.25)		0.2110-0.3310	29 (32.58)	33 (25.42)	1.44 (0.69-3.00)
0.3265-0.4888	49 (21.12)	66 (25.00)	1.41 (0.82-2.43)		0.3433-0.4908	28 (21.21)	30 (25.42)	1.54 (0.70-3.38)		0.3310-0.4948	16 (17.98)	33 (25.42)	1.83 (0.80-4.23)
> 0.4888	26 (11.21)	66 (25.00)	3.54 (1.84-6.82)		> 0.4908	12 (9.09)	29 (24.58)	3.40 (1.32-8.73)		> 0.4948	13 (14.61)	32 (24.58)	3.33 (1.31-8.46)

¹Serum positivity for the antibodies to KatA and AhpC was categorized by quartiles of antibody levels in controls;

²Adjusted for age, sex, family history of gastric cancer, smoking, and alcohol consumption. H. pylori: Helicobacter pylori; KatA: Catalase; AhpC: Alkyl hydroperoxide reductase.

Table 3 Sensitivity and specificity of different catalase and alkyl hydroperoxide reductase critical values

Percentile1	All subjects			H. pylori positive subjects			H. pylori negative subjects
	Critical value (OD)2	Sensitivity	Specificity	Critical value (OD)2	Sensitivity	Specificity	Critical value (OD)2	Sensitivity	Specificity
KatA
Optimal cutoff point2	0.3583	66.81%	86.36%	0.3557	64.39%	88.14%	0.3730	70.79%	83.85%
25%	0.2800	46.55%	93.18%	0.4152	69.70%	74.58%	0.2773	50.56%	90.00%
50%	0.4305	75.00%	71.59%	0.5133	87.12%	49.15%	0.4447	78.65%	69.23%
75%	0.5958	90.95%	36.36%	0.6692	93.94%	24.58%	0.6107	92.13%	36.15%
90%	0.7418	97.84%	16.29%	0.9042	100.00%	8.47%	0.7873	97.75%	14.62%
AhpC
Optimal cutoff point2	0.3647	75.65%	45.49%	0.3613	75.76%	48.31%	0.2330	43.82%	70.77%
25%	0.1953	30.43%	78.95%	0.1953	30.30%	80.51%	0.1917	30.34%	77.69%
50%	0.2830	59.57%	57.14%	0.2865	59.85%	60.17%	0.2913	62.92%	57.69%
75%	0.4267	84.35%	32.71%	0.4325	83.33%	33.05%	0.4313	85.39%	23.85%
90%	0.5747	95.65%	14.29%	0.5302	93.94%	13.56%	0.6410	96.63%	13.85%

¹Percentiles of serum KatA and AhpC antibody levels in controls;

²Optimal cutoff point in the different parameters was identified according to the maximum Youden’s index (sensitivity + specificity - 1). H. pylori: Helicobacter pylori; KatA: Catalase; AhpC: Alkyl hydroperoxide reductase.