Homologous recombination deficiency and immunotherapy response in microsatellite-stable colorectal cancer: Evidence from a cohort study in China

Table 1 Clinical and next-generation sequencing characteristics of colorectal cancer in the homologous recombination proficient and homologous recombination deficiency groups, n (%)

Variables	All	HRP group	HRD group	P value
	n = 268	n = 204	n = 64
Gender				0.64
Male	170 (63.43)	131 (64.22)	39 (60.94)
Female	98 (36.57)	73 (35.78)	25 (39.06)
Age (years)				0.05a
≤ 60	178 (66.42)	129 (63.24)	49 (76.56)
> 60	90 (33.58)	75 (36.76)	15 (23.44)
BMI				0.16
< 18.5	16 (5.97)	9 (4.41)	7 (10.94)
18.5-24	161 (60.07)	124 (60.78)	37 (57.81)
> 24	91 (33.96)	71 (34.80)	20 (31.25)
Differentiation				0.07
Poorly	47 (17.54)	31 (15.20)	16 (25.00)
Moderately & well & chronic inflammation after neoadjuvant therapy	221 (82.46)	173 (84.80)	48 (75.00)
Pathological type				< 0.01a
Adenocarcinoma	216 (80.60)	173 (84.80)	43 (67.19)
Special histologic type adenocarcinoma	14 (5.22)	6 (2.94)	8 (12.50)
Mixed	30 (11.19)	21 (10.30)	9 (14.06)
Chronic inflammation after neoadjuvant therapy	8 (2.99)	4 (1.96)	4 (6.25)
Tumor location				< 0.01a
Left colon	196 (73.13)	159 (77.94)	37 (57.81)
Right colon	69 (25.75)	43 (21.08)	26 (40.63)
Mixed	3 (1.12)	2 (0.98)	1 (1.56)
Tumor size/max				0.27
≥ 4 cm	160 (59.70)	118 (57.84)	42 (65.63)
< 4 cm	108 (40.30)	86 (42.16)	22 (34.37)
AJCC stage				< 0.01a
I	12 (4.48)	4 (1.96)	8 (12.50)
II	37 (13.81)	24 (11.76)	13 (20.31)
III	75 (27.99)	58 (28.43)	17 (26.56)
IV	144 (53.72)	118 (57.84)	26 (40.63)
Tumor depth				0.07
T1&T2&T3	120 (44.78)	85 (41.67)	35 (54.69)
T4	148 (55.22)	119 (58.33)	29 (45.31)
Lymph node metastasis				0.02a
N0	60 (22.39)	39 (19.12)	21 (32.81)
N1 & N2	208 (77.61)	165 (80.88)	43 (67.19)
Metastasis				0.01a
M0	127 (47.39)	88 (43.14)	39 (60.94)
M1	141 (52.61)	116 (56.86)	25 (39.06)
BRAF status				0.63
V600E Mut	6 (2.24)	4 (1.96)	2 (3.13)
Wt	262 (97.76)	200 (98.04)	62 (96.87)
RAS status				0.62
Mut	137 (51.12)	106 (51.96)	31 (48.44)
Wt	131 (48.88)	98 (48.04)	33 (51.56)
erb-B2 status				< 0.01a
Mut	4 (1.49)	0 (0.00)	4 (6.25)
Wt	264 (98.51)	204 (100.00)	60 (93.75)
MSI status				< 0.01a
MSI-H	27 (10.07)	1 (0.49)	26 (40.63)
MSS	241 (89.93)	203 (99.51)	38 (59.37)
TMB level (median with IQR)	6.15 (4.47,8.94)	5.59 (3.91,7.82)	24.58 (6.15,87.57)	< 0.01a

^aP < 0.05.

HRD: Homologous recombination deficiency; HRP: Homologous recombination proficient; Mut: Mutation; Wt: Wild type; MSI: Microsatellite instability; TMB: Tumor mutation burden; BMI: Body mass index.

Table 2 Univariate and multivariable Cox regression analysis of predicting progression-free survival in patients with microsatellite-stable colorectal cancer treated with immune checkpoint inhibitors

Variable	Univariable			Multivariable
	HR	95%CI	P value	HR	95%CI	P value
Gender (female vs male)	1.52	0.69-3.31	0.30
Age (> 60 vs ≤ 60 years)	1.25	0.56-2.81	0.59
BMI
< 18.5	Reference
18.5-24	2.70	0.36-20.43	0.34
> 24	3.49	0.41-29.75	0.25
Differentiation (moderately & well & chronic inflammation after neoadjuvant therapy vs poorly)	0.41	0.12-1.37	0.15
Pathological type
Chronic inflammation after neoadjuvant therapy	Reference
Adenocarcinoma	1.58	0.21-11.88	0.66
Special histologic type adenocarcinoma	0.63	0.06-7.00	0.71
Mixed	0.66	0.04-10.75	0.77
Tumor location
Left colon	Reference
Right colon	0.72	0.31-1.65	0.44
Mixed	4.58	0.54-38.86	0.16
Tumor size (< 4 cm vs ≥ 4 cm)	0.45	0.17-1.19	0.11
AJCC stage (III& IV vs I& II)	2.04	0.59-7.01	0.26
HRD (yes vs no)	0.31	0.09-1.03	0.06	0.31	0.09-1.03	0.05a

^aP ≤ 0.05.

HRD: Homologous recombination deficiency; BMI: Body mass index.