Free Fatty Acid is a Promising Biomarker in Triage Screening for Patients with Colorectal Cancer: A Case–Control Study

Figures & data

Table 1 Baseline Characteristics of the Study Population Including Healthy Participants and Patients with Colorectal Adenomas and CRC in This Study

Parameter	Normal (n=330)	CA (n=612)	CRC (n=1023)		P value
Male	210	399	647		0.724^a
Female	120	213	376
Age (Years), Median (Range)	59 (49–68)	60 (50–67)	59 (50–68)		0.241^b
BMI (kg/m2), Median (Range)	23.11 (19.92–25.91)	23.51 (19.79–25.87)	23.91 (19.02–26.69)		0.294^b
CEA (ng/mL), Mean±SD	1.95±1.03	3.21±6.64	14.39±47.61		<0.001^b
CA19-9 (U/mL), Mean±SD	10.50±6.69	15.58±42.60	39.26±101.8		<0.001^b
FFA (mmol/L) Mean±SD	0.48±0.22	0.49±0.22	0.58±0.27		<0.001^b
Tumour TNM stage (n, %)	/	/	I	142 (13.9%)	/
			II	236 (23.1%)
			III	471 (46.0%)
			IV	174 (17.0%)
Tumour location (n, %)	/	/	Colon	388 (37.9%)	/
			Rectum	635 (62.1%)
Tumour sizes (n, %)	/	/	<5 cm	370 (36.2%)	/
			≥5 cm	653 (63.8%)
Lymph node metastasis (n, %)	/	/	No	594 (58.1%)	/
			Yes	429 (41.9%)

Notes: ^aThe chi-square test was performed to analyse significant differences. ^bOne-way ANOVA was performed to analyse significant differences.

Abbreviations: CA, colorectal adenoma; CRC, colorectal cancer; BMI, body mass index; CEA, carcinoembryonic antigen; CA19-9, cancer antigen 19-9; TNM, tumour-node-metastasis, SD, standard deviation.

Figure 1 FFA levels in controls and CRC patients according to age (<35, 36–50, 51–65, and >66 years). The differences between groups (normal vs CA, normal vs CRC and CA vs CRC) were analysed by Student’s t test. One-way ANOVA was used to analyse significant differences among the normal, CA and CRC groups. The LSD-t test was used for post hoc comparisons of different age groups. *, <0.05; **, <0.01; ***, <0.001. A–D: FFA level differences between Normal, CA and CRC in groups of Age_<35, Age_36-50, Age _51-65, Age _>66. E–G: FFA level differences from patients younger than age 35 to older than 66 in groups of Normal, CA and CRC.

Abbreviations: CA, colorectal adenoma; CRC, colorectal cancer; Ns, no significant difference.

Table 2 The Values of FFA, CEA, and CA19-9 Alone and Combined Biomarkers for Distinguishing CRC Patients from Healthy Participants and Patients with Colorectal Adenomas from 21 to 88 Years Old

Variables	AUC	Cut-Off	Sensitivity%	Specificity%	95% Confidence Interval
					Lower Limit	Upper Limit
FFA	0.604	0.585	41.6	73.1	58.2	62.6
CA19-9	0.640	37	45.7	77.3	61.8	66.2
CEA	0.731	5	55.8	81.1	71.0	75.1
FFA+CA19-9	0.678	/	50.3	75.8	65.7	69.9
FFA+CEA	0.754	/	49.5	90.4	73.5	77.4
FFA+CEA+CA19-9	0.758	/	53.9	87.3	73.9	77.8

Abbreviation: AUC, area under the curve.

Figure 2 ROC curves of single and combined detection with FFA, CEA and CA19-9 in patients 21 to 88 years old. ROC curve analysis was used to evaluate the ability to distinguish patients with CRC from controls. Patients with CA and healthy participants were considered as controls.

Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9.

Table 3 The Values of FFA, CEA, and CA19-9 Alone and Combined Biomarkers for Distinguishing CRC Patients from Healthy Participants and Patients with Colorectal Adenomas Younger Than or Equal to 50 Years Old

Variables	AUC	Cut-Off	Sensitivity%	Specificity%	95% Confidence Interval
					Lower Limit	Upper Limit
FFA	0.701	0.585	48.7	84.5	66.1	74.1
CA19-9	0.667	37	48.3	81.6	62.4	71.1
CEA	0.734	5	50.4	87.5	69.3	77.4
FFA+CA19-9	0.749	/	67.4	79.1	71.1	78.7
FFA+CEA	0.798	/	59.2	81.8	76.3	83.4
FFA+CEA+CA19-9	0.801	/	68.2	79.3	76.5	83.6

Abbreviation: AUC, area under the curve.

Figure 3 ROC curves for single and combined detection with FFA, CEA and CA19-9 in patients younger than 50 years old. ROC curve analysis was used to evaluate the ability to distinguish patients with CRC from controls among those younger than 50 years. Patients with CA and healthy participants were considered as controls.

Table 4 Ability of Serological Biomarkers to Predict CRC in Patients Younger or Older Than 50 Years

Variables	No. of Patients	Cutoff Value	Multivariate Analysis
			OR ajusted ^a	95% Cl	P value
Younger than 50 years old
FFA (mmol/L)	367	<0.585	1 (R)	–
	144	>0.585	5.210	3.661–7.413	0.001
CEA (ng/mL)	375	<5	1 (R)	–
	136	>5	7.068	4.879–10.239	0.001
CA19-9 (U/mL)	364	<37	1 (R)	–
	147	>37	4.298	3.039–6.080	0.001
Older than 50 years old
FFA (mmol/L)	944	<0.585	1 (R)	–
	510	>0.585	1.421	1.174–1.720	0.001
CEA (ng/mL)	896	<5	1 (R)	–
	558	>5	5.073	4.151–6.199	0.001
CA19-9 (U/mL)	977	<37	1 (R)	–
	477	>37	2.533	2.085–3.076	0.001

Note: ^aAdjusted ORs were obtained using the regression coefficients from a multivariable logistic regression model and were adjusted by age.

Abbreviation: OR, odds ratio.

Figure 4 FFA levels in controls and CRC patients according to sex; ROC curves of FFA and CEA in patients younger than 50 years according to sex. The differences between groups (normal vs CA, normal vs CRC and CA vs CRC) were analysed by Student’s t test. The ROC curve of CEA and FFA was used to evaluate the ability to distinguish patients with CRC from controls among patients younger than 50 years. Patients with CA and healthy participants were considered as controls. *, <0.05; ***, <0.001.

Abbreviation: Ns, no significant difference.