Association between gut microbial dysbiosis and clinical prognosis of advanced colorectal cancer

Table 1 Comparison of clinicopathological and treatment-related data of patients with advanced colorectal cancer between the two groups, median (interquartile range)/n(%)

Variable	Normal flora group (n = 48)	Abnormal flora group (n = 76)	Z/χ2	P value
Demographic characteristics
Male	27 (56.25)	45 (59.21)	0.106	0.745
Age (years)	63.5 (54.25, 71.75)	60.00 (53.00, 72.00)	0.703	0.482
BMI (kg/m2)	22.82 (21.34, 26.02)	22.82 (19.87, 25.51)	0.972	0.331
Smoking history	15 (31.25)	26 (34.21)	0.117	0.733
Drinking history	13 (27.08)	24 (31.58)	0.284	0.594
Hypertension	14 (29.17)	24 (31.58)	0.081	0.777
Type 2 diabetes mellitus	7 (14.58)	15 (19.74)	0.535	0.464
Tumor pathological characteristics
Primary tumor site			0.041	0.905
Colon	26 (54.17)	42 (55.26)
Rectum	22 (45.83)	34 (44.74)
Maximum tumor diameter (cm)	4.65 (4.06, 6.14)	4.92 (3.79, 5.87)	0.693	0.489
Histological differentiation			11.297	0.001
Well/moderate differentiation	39 (81.25)	39 (51.32)
Poor differentiation	9 (18.75)	37 (48.68)
TNM staging			10.728	0.001
IIIB-IIIC	37 (77.08)	36 (47.37)
IV	11 (22.92)	40 (52.63)
Positive vascular invasion	15 (31.25)	44 (57.89)	8.374	0.004
Positive perineural invasion	13 (27.08)	39 (51.32)	7.095	0.008
Elevated preoperative CEA	28 (58.33)	50 (65.79)	0.701	0.402
Elevated preoperative CA19-9	25 (52.08)	44 (57.89)	0.403	0.526
Treatment regimen			0.043	0.979
Radical resection + adjuvant chemotherapy	23 (47.92)	35 (46.05)
Palliative chemotherapy	16 (33.33)	26 (34.21)
Chemotherapy combined with targeted therapy	9 (18.75)	15 (19.74)

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9.

Table 2 Comparison of short-chain fatty acid and secondary bile acid levels in the two groups of patients, mean ± SD

Group	n	Short-chain fatty acids (mmol/L)	Secondary bile acids (μmol/L)
Normal flora group	48	31.82 ± 6.35	22.15 ± 4.26
Abnormal flora group	76	19.24 ± 5.12	44.87 ± 7.32
t value	-	12.129	19.502
P value	-	< 0.001	< 0.001

Table 3 Univariate Cox regression analysis of factors influencing overall survival in patients with advanced colorectal cancer

Variable	β	SE	HR	95%CI	P value
Gender (male = 1, female = 0)	0.215	0.247	1.240	0.762-2.017	0.385
Age (≥ 65 years = 1, < 65 years = 0)	0.207	0.239	1.230	0.769-1.967	0.387
BMI (< 18.5 kg/m2 = 1, others = 0)	0.312	0.406	1.366	0.616-3.029	0.443
Smoking history (yes = 1, no = 0)	0.186	0.249	1.204	0.739-1.961	0.456
Drinking history (yes = 1, no = 0)	0.154	0.257	1.166	0.704-1.931	0.549
Hypertension (yes = 1, no = 0)	0.178	0.245	1.195	0.738-1.934	0.468
Type 2 diabetes mellitus (yes = 1, no = 0)	0.286	0.284	1.331	0.762-2.325	0.314
Primary tumor site (rectum = 1, colon = 0)	0.103	0.234	1.108	0.700-1.755	0.660
Maximum tumor diameter (≥ 5 cm = 1, < 5 cm = 0)	0.225	0.235	1.253	0.790-1.986	0.338
Histological differentiation (poor = 1, well/moderate = 0)	0.758	0.300	2.135	1.187-3.840	0.011
TNM staging (IV = 1, IIIB-IIIC = 0)	1.016	0.282	2.763	1.586-4.813	< 0.001
Vascular invasion (positive = 1, negative = 0)	0.700	0.282	2.014	1.159-3.497	0.013
Perineural invasion (positive = 1, negative = 0)	0.656	0.279	1.927	1.117-3.325	0.018
Elevated preoperative CEA (yes = 1, no = 0)	0.327	0.240	1.387	0.866-2.220	0.174
Elevated preoperative CA19-9 (yes = 1, no = 0)	0.349	0.238	1.418	0.889-2.261	0.142
Gut microbial dysbiosis (yes = 1, no = 0)	1.055	0.292	2.872	1.621-5.086	< 0.001
Radical resection (no = 1, yes = 0)	0.974	0.283	2.648	1.517-4.621	< 0.001

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; HR: Hazard ratio.

Table 4 Multivariate Cox regression analysis of factors influencing overall survival in patients with advanced colorectal cancer

Variable	β	SE	HR	95%CI	P value
Age (≥ 65 years = 1)	0.211	0.325	1.235	0.653-2.337	0.524
Elevated preoperative CEA (yes = 1)	0.204	0.318	1.226	0.658-2.284	0.519
Chemotherapy regimen (combined with targeted therapy = 1)	0.187	0.321	1.206	0.642-2.267	0.558
Histological differentiation (poor = 1, well/moderate = 0)	0.686	0.319	1.985	1.062-3.712	0.031
TNM staging (IV = 1, IIIB-IIIC = 0)	0.782	0.316	2.187	1.176-4.068	0.013
Gut microbial dysbiosis (yes = 1, no = 0)	0.839	0.310	2.314	1.258-4.259	0.007
Radical resection (no = 1, yes = 0)	0.810	0.317	2.246	1.203-4.192	0.011

HR: Hazard ratio; CEA: Carcinoembryonic antigen.

Table 5 Comparison of first-line systemic chemotherapy efficacy and clinical benefit rates between the two groups, n (%)

Efficacy index	Normal flora group (n = 38)	Abnormal flora group (n = 58)	χ2 value	P value
CR	3 (7.89)	2 (3.45)	-	0.631
PR	19 (50.00)	17 (29.31)	-	-
SD	12 (31.58)	20 (34.48)	-	-
PD	4 (10.53)	19 (32.76)	-	-
ORR	22 (57.89)	19 (32.76)	5.984	0.014
DCR	34 (89.47)	39 (67.24)	5.872	0.015

CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Objective response rate; DCR: Disease control rate.

Table 6 Comparison of first-line chemotherapy efficacy between the two groups in subgroups with different driver gene statuses, n (%)

Group	n	RAS-mutantion		n	BRAF V600E mutation		n	Wild-type
		ORR	DCR		ORR	DCR		ORR	DCR
Normal flora group	22	12 (54.55)	19 (86.36)	3	1 (33.33)	2 (66.67)	23	15 (65.22)	21 (91.30)
Abnormal flora group	24	10 (29.41)	21 (61.76)	7	0 (0.00)	2 (28.57)	35	12 (34.29)	24 (68.57)
χ2 value	-	3.538	3.960	-	-	-	-	5.337	4.125
P value	-	0.060	0.047	-	0.300	0.500	-	0.021	0.042

ORR: Objective response rate; DCR: Disease control rate.