Intertwined leukocyte balances in tumours and peripheral blood as robust predictors of right and left colorectal cancer survival

Table 1 Baseline characteristics of patients included in this study

Characteristics		Frequency	%
All patients (n = 65)
Age (yr) ± SD		73.54 ± 9.51
(range)		(52-92)
Gender
Female		29	44.62
Male		36	55.38
Tumour localisation
Right colorectal cancer		43	66.15
Caecum		13	30.23
Ascending colon		23	53.49
Transverse colon		7	16.28
Left colorectal cancer		22	33.85
Descending colon		11	50.00
Sigma		11	50.00
Emergency surgery
Yes		1	1.54
No		64	98.46
Surgical procedure
Laparoscopic hemicolectomy		48	73.85
Open hemicolectomy		17	26.15
Development at surgery
Non-metastasised		37	56.92
Metastases		28	43.08
Liver synchronous		13	46.43
Liver metachronous		8	28.57
Other organs		13	46.43
MMR status
pMMR		56	86.15
dMMR		5	7.69
Unknown		4	6.15
TNM stage
0		3	4.62
I		7	10.77
IIA		21	32.31
IIB		5	7.69
IIIA		2	3.08
IIIB		8	12.31
IIIC		5	7.69
IV		1	1.54
IVA		10	15.38
IVB		3	4.62
Adjuvant chemotherapy
Yes		30	46.15
No		35	53.85
Blood leukocytes counting (× 103/μL), (normal range)	RCRC	LCRC	P value
White blood cells count (3.6-10.5)	7.41 (3.52-16.2)	8.19 (4.83-15.8)	0.271
Lymphocytes (1.1-4.5)	1.77 (0.46-4.46)	2.04 (0.32-4.87)	0.235
Monocytes (0.1-0.9)	0.54 (0.20-1.26)	0.50 (0.22-1.11)	0.493
Neutrophils (1.5-7.7)	4.86 (1.76-15.3)	5.34 (2.96-13.0)	0.480
Platelets (150-370)	275.65 (101.0-602.0)	272.41 (142.0-725.0)	0.910
LMRb	3.54 (0.42-7.96)	4.64 (0.58-11.88)	0.046
NLRb	3.65 (0.69-25.93)	4.61 (0.93-30.66)	0.481
PLRb	188.58 (52.24-551.22)	213.93 (29.16-1187.50)	0.585

TNM: Tumour-nodes-metastasis classification; MMR: DNA mismatch repair; pMMR: Proficient MMR; dMMR: Deficient MMR; LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophil-to-lymphocytes ratio; PLR: Platelet-to-lymphocyte ratio; RCRC: Right-sided colorectal cancer; LCRC: Left-sided colorectal cancer; SD: Standard deviation; b: Blood.

Table 2 Association of leukocytes counts and ratios with overall and recurrence-free survival

Index	Total patients	4-year OS				4-year RFS
	n (%)	Spearman r	95%CI	P		Spearman r	95%CI	P
LMRb
Right	43 (66.2)	-0.3039	-0.5601 to 0.005346	0.0476	< 0.05	-0.1946	-0.4748 to 0.1214	0.211	NS
Left	22 (33.8)	0.1615	-0.2914 to 0.5553	0.4727	NS	-0.07447	-0.4912 to 0.3700	0.7419	NS
NLRb
Right	43 (66.2)	0.2262	-0.08868 to 0.5000	0.1446	NS	0.1062	-0.2094 to 0.4017	0.498	NS
Left	22 (33.8)	-0.06922	-0.4872 to 0.3746	0.7595	NS	0.1192	-0.3305 to 0.5247	0.5974	NS
PLRb
Right	43 (66.2)	0.2307	-0.08405 to 0.5035	0.1367	NS	0.06684	-0.2470 to 0.3680	0.6702	NS
Left	22 (33.8)	0.1615	-0.2914 to 0.5553	0.4727	NS	0.1192	-0.3305 to 0.5247	0.5974	NS
CD4t
Right	34 (63.0)	-0.05561	-0.3954 to 0.2976	0.7548	NS	0.05447	-0.2986 to 0.3944	0.7596	NS
Left	20 (37.0)	0.01892	-0.4387 to 0.4687	0.9369	NS	-0.0354	-0.4815 to 0.4253	0.8822	NS
CD4pt
Right	34 (63.0)	0.03708	-0.3144 to 0.3796	0.8351	NS	0.07371	-0.2809 to 0.4106	0.6787	NS
Left	20 (37.0)	-0.142	-0.5597 to 0.3334	0.5505	NS	0.3276	-0.1483 to 0.6803	0.1586	NS
CD8t
Right	34 (63.0)	-0.08526	-0.4202 to 0.2702	0.6316	NS	-0.2083	-0.1958 to 0.6531	0.2372	NS
Left	20 (37.0)	0.03784	-0.4233 to 0.4834	0.8741	NS	0.2832	-0.3863 to 0.3074	0.2263	NS
CD8pt
Right	34 (63.0)	-0.1186	-0.4476 to 0.2386	0.504	NS	-0.04486	-0.3863 to 0.3074	0.8011	NS
Left	20 (37.0)	0.3406	-0.1340 to 0.6881	0.1417	NS	0.3186	-0.1581 to 0.6749	0.171	NS
CD4CD8t
Right	34 (63.0)	-0.1372	-0.4626 to 0.2208	0.4392	NS	-0.1955	-0.5084 to 0.1630	0.268	NS
Left	20 (37.0)	0.03784	-0.4233 to 0.4834	0.8741	NS	0.2655	-0.2142 to 0.6420	0.2579	NS
CD4CD8pt
Right	34 (63.0)	-0.07044	-0.4079 to 0.2839	0.6922	NS	-0.009612	-0.3559 to 0.3389	0.957	NS
Left	20 (37.0)	0.3595	-0.1127 to 0.6993	0.1195	NS	0.4425	-0.01421 to 0.7464	0.0507	NS
CD14t
Right	34 (63.0)	0.1891	-0.1695 to 0.5034	0.2842	NS	0.2467	-0.1102 to 0.5472	0.1595	NS
Left	20 (37.0)	0.05677	-0.4076 to 0.4978	0.8121	NS	-0.1239	-0.5470 to 0.3496	0.6028	NS
CD14pt
Right	34 (63.0)	0.3003	-0.05262 to 0.5865	0.0844	NS	0.2596	-0.09658 to 0.5568	0.1382	NS
Left	20 (37.0)	0.5677	0.1533 to 0.8122	0.009	< 0.01	0.6018	0.2035 to 0.8292	0.005	< 0.01
LMRt
Right	34 (63.0)	-0.2929	-0.5812 to 0.06070	0.0927	NS	-0.4775	-0.7075 to -0.1559	0.0043	< 0.01
Left	20 (37.0)	0.07569	-0.3916 to 0.5119	0.7511	NS	0.4425	-0.01421 to 0.7464	0.0507	NS
LMRpt
Right	34 (63.0)	-0.4301	-0.6764 to -0.09719	0.0111	< 0.05	-0.3846	-0.6457 to -0.04285	0.0247	< 0.05
Left	20 (37.0)	0	-0.4538 to 0.4538	> 0.9999	NS	-0.0354	-0.4815 to 0.4253	0.8822	NS
CD4MRt
Right	34 (63.0)	-0.2781	-0.5704 to 0.07674	0.1113	NS	-0.3173	-0.5987 to 0.03388	0.0675	NS
Left	20 (37.0)	0.04736	-0.4154 to 0.4907	0.8428	NS	0.1949	-0.2841 to 0.5960	0.4102	NS
CD4MRpt
Right	34 (63.0)	-0.2781	-0.5704 to 0.07670	0.1112	NS	-0.2596	-0.5568 to 0.09650	0.1381	NS
Left	20 (37.0)	-0.473	-0.7631 to -0.02445	0.0352	NS	-0.0885	-0.5214 to 0.3806	0.7106	NS
CD8MRt
Right	34 (63.0)	-0.2039	-0.5149 to 0.1545	0.2474	NS	-0.4422	-0.6845 to -0.1120	0.0088	< 0.01
Left	20 (37.0)	0.1135	-0.3588 to 0.5396	0.6337	NS	0.4779	0.03071 to 0.7657	0.0331	< 0.05
CD8MRpt
Right	34 (63.0)	-0.3596	-0.6285 to -0.01393	0.0367	< 0.05	-0.2788	-0.5709 to 0.07601	0.1104	NS
Left	20 (37.0)	0.1893	-0.2894 to 0.5923	0.4241	NS	-0.03541	-0.4815 to 0.4253	0.8822	NS
LMRb/LMRt
Right	34 (63.0)	0.1075	-0.2492 to 0.4386	0.545	NS	0.3621	0.01678 to 0.6302	0.0353	< 0.05
Left	20 (37.0)	-0.05677	-0.4978 to 0.4076	0.8121	NS	-0.4248	-0.7366 to 0.03599	0.0619	NS
LMRb/LMRpt
Right	34 (63.0)	0.241	-0.1162 to 0.5430	0.1698	NS	0.2884	-0.06561 to 0.5779	0.0981	NS
Left	20 (37.0)	0.1325	-0.3420 to 0.5531	0.5778	NS	-0.0531	-0.4950 to 0.4106	0.8241	NS
LMRb/CD4MRt
Right	34 (63.0)	0.1372	-0.2208 to 0.4626	0.4392	NS	0.2467	-0.1101 to 0.5473	0.1595	NS
Left	20 (37.0)	-0.09461	-0.5259 to 0.3754	0.6915	NS	-0.177	-0.5839 to 0.3010	0.4554	NS
LMRb/CD4MRpt
Right	34 (63.0)	0.1446	-0.2136 to 0.4685	0.4146	NS	0.189	-0.1695 to 0.5034	0.2843	NS
Left	20 (37.0)	0.4541	0.0003499 to 0.7528	0.0443	< 0.05	0.1062	-0.3653 to 0.5343	0.6559	NS
LMRb/CD8MRt
Right	34 (63.0)	0.04078	-0.3111 to 0.3828	0.8189	NS	0.3364	-0.01245 to 0.6123	0.0517	NS
Left	20 (37.0)	-0.03784	-0.4834 to 0.4233	0.8741	NS	-0.4071	-0.7267 to 0.05735	0.0748	NS
LMRb/CD8MRpt
Right	34 (63.0)	0.1409	-0.2172 to 0.4655	0.4267	NS	0.1859	-0.1727 to 0.5009	0.2926	NS
Left	20 (37.0)	-0.1703	-0.5794 to 0.3073	0.4729	NS	-0.1416	-0.5595 to 0.3337	0.5515	NS

OS: Overall survival; RFS: Recurrence-free survival; LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophil-to-lymphocytes ratio; PLR: Platelet-to-lymphocyte ratio; b: Blood; t: Tumour; pt: Peritumour; CD4MR: CD4⁺-lymphocyte-to-monocyte ratio; CD8MR: CD8⁺-lymphocyte-to-monocyte ratio; CI: Confidence interval; NS: Not significant.

Table 3 Univariate and multivariate analyses for prognostic variables of overall survival after surgical interventions of right-sided colorectal cancer and left-sided colorectal cancer

	Total patients	Univariate analysis					Multivariate analysis
	n (%)	HR	95%CI		P		HR	95%CI		P
Variables			Low	High				Low	High
LMRb
Right	34 (63.0)	0.565	0.325	0.982	0.043	< 0.05	0.133	0.000	71.041	0.529
Left	20 (37.0)	1.141	0.867	1.502	0.346		1.141	0.867	1.502	0.346
NLRb
Right	34 (63.0)	1.416	1.019	1.967	0.038	< 0.05	1.416	1.019	1.967	0.038	< 0.05
Left	20 (37.0)	1.043	0.944	1.152	0.410		1.126	0.987	1.284	0.078
PLRb
Right	34 (63.0)	1.005	1.000	1.011	0.064		0.989	0.719	1.361	0.946
Left	20 (37.0)	1.001	0.999	1.004	0.292		0.997	0.937	1.060	0.912
CD4t
Right	34 (63.0)	0.923	0.638	1.334	0.670
Left	20 (37.0)	0.843	0.493	1.439	0.531
CD4pt
Right	34 (63.0)	0.959	0.817	1.124	0.604
Left	20 (37.0)	0.813	0.454	1.456	0.487
CD8t
Right	34 (63.0)	0.995	0.897	1.105	0.931		1.032	0.913	1.167	0.611
Left	20 (37.0)	0.954	0.860	1.057	0.364
CD8pt
Right	34 (63.0)	0.792	0.617	1.016	0.066		0.800	0.636	1.007	0.058
Left	20 (37.0)	1.018	0.957	1.083	0.570		1.033	0.962	1.110	0.372
CD4CD8t
Right	34 (63.0)	0.987	0.892	1.093	0.806
Left	20 (37.0)	0.937	0.833	1.054	0.277
CD4CD8pt
Right	34 (63.0)	0.891	0.761	1.043	0.150		1.073	0.821	1.401	0.606
Left	20 (37.0)	1.015	0.953	1.082	0.641
CD14t
Right	34 (63.0)	1.048	0.845	1.300	0.670		1.077	0.836	1.388	0.565
Left	20 (37.0)	0.979	0.703	1.362	0.898
CD14pt
Right	34 (63.0)	1.113	0.889	1.394	0.351		1.342	0.987	1.826	0.060
Left	20 (37.0)	1.053	0.723	1.533	0.788		0.700	0.381	1.286	0.250
LMRt
Right	34 (63.0)	0.635	0.365	1.103	0.107
Left	20 (37.0)	1.000	0.908	1.101	0.997		0.976	0.555	1.716	0.933
LMRpt
Right	34 (63.0)	0.416	0.194	0.889	0.024	< 0.05
Left	20 (37.0)	1.030	0.712	1.490	0.876		0.031	0.000	4.228	0.166
CD4MRt
Right	34 (63.0)	0.270	0.039	1.850	0.182
Left	20 (37.0)	0.759	0.146	3.954	0.743
CD4MRpt
Right	34 (63.0)	0.431	0.112	1.660	0.221
Left	20 (37.0)	0.135	0.004	4.148	0.252
CD8MRt
Right	34 (63.0)	0.712	0.364	1.394	0.321
Left	20 (37.0)	1.001	0.910	1.100	0.986
CD8MRpt
Right	34 (63.0)	0.223	0.057	0.872	0.031	< 0.05	0.024	0.001	0.430	0.011	< 0.05
Left	20 (37.0)	1.078	0.775	1.500	0.654
LMRb/LMRt
Right	34 (63.0)	0.957	0.603	1.519	0.853
Left	20 (37.0)	1.163	0.935	1.446	0.175
LMRb/LMRpt
Right	34 (63.0)	1.253	0.824	1.907	0.292
Left	20 (37.0)	1.196	0.845	1.695	0.313
LMRb/CD4MRt
Right	34 (63.0)	1.009	0.950	1.073	0.767		1.282	0.931	1.765	0.128
Left	20 (37.0)	1.027	0.961	1.099	0.428
LMRb/CD4MRpt
Right	34 (63.0)	1.028	0.926	1.142	0.600		1.291	0.447	3.728	0.636
Left	20 (37.0)	1.097	1.011	1.190	0.026	< 0.05	0.991	0.420	2.341	0.984
LMRb/CD8MRt
Right	34 (63.0)	0.973	0.747	1.269	0.842
Left	20 (37.0)	1.103	0.940	1.294	0.229		1.971	0.258	15.069	0.513
LMRb/CD8MRpt
Right	34 (63.0)	1.053	0.880	1.260	0.572		0.484	0.268	0.873	0.016	< 0.05
Left	20 (37.0)	1.026	0.834	1.262	0.812		0.952	0.009	96.530	0.983

LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophil-to-lymphocytes ratio; PLR: Platelet-to-lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval; b: Blood; t: Tumour; pt: Peritumour; CD4MR: CD4⁺-lymphocyte-to-monocyte ratio; CD8MR: CD8⁺-lymphocyte-to-monocyte ratio.

Table 4 Univariate and multivariate analyses for prognostic variables of recurrence-free survival after surgical interventions of right-sided colorectal cancer and left-sided colorectal cancer

	Total patients	Univariate analysis					Multivariate analysis
	n (%)	HR	95%CI		P		HR	95%CI		P
Variables			Low	High				Low	High
LMRb
Right	34 (63.0)	0.865	0.593	1.262	0.453
Left	20 (37.0)	0.977	0.770	1.239	0.848		0.156	0.001	24.118	0.470
NLRb
Right	34 (63.0)	1.135	0.841	1.532	0.407		2.760	1.050	7.254	0.039	< 0.05
Left	20 (37.0)	1.094	1.094	1.180	0.020	< 0.05	1.156	1.038	1.288	0.009	< 0.01
PLRb
Right	34 (63.0)	1.001	0.996	1.007	0.596		0.978	0.958	0.999	0.037	< 0.05
Left	20 (37.0)	1.002	1.000	1.004	0.018	< 0.05	0.987	0.954	1.022	0.468
CD4t
Right	34 (63.0)	1.010	0.864	1.181	0.902		0.802	0.457	1.407	0.441
Left	20 (37.0)	0.981	0.617	1.559	0.934
CD4pt
Right	34 (63.0)	0.963	0.851	1.091	0.556		1.486	0.124	17.828	0.755
Left	20 (37.0)	1.120	0.795	1.577	0.516
CD8t
Right	34 (63.0)	0.962	0.872	1.062	0.446		1.821	0.451	7.347	0.400
Left	20 (37.0)	1.032	0.971	1.097	0.310
CD8pt
Right	34 (63.0)	0.906	0.780	1.053	0.199		1.117	0.848	1.472	0.431
Left	20 (37.0)	1.050	0.988	1.115	0.116		1.098	1.015	1.189	0.020	< 0.05
CD4CD8t
Right	34 (63.0)	0.972	0.893	1.058	0.515
Left	20 (37.0)	1.033	0.970	1.100	0.307		0.436	0.198	0.960	0.039	< 0.05
CD4CD8pt
Right	34 (63.0)	0.944	0.857	1.041	0.248
Left	20 (37.0)	1.052	0.992	1.117	0.093		0.008	0.000	1.071	0.053
CD14t
Right	34 (63.0)	1.123	0.949	1.329	0.178		1.467	1.048	2.054	0.026	< 0.05
Left	20 (37.0)	0.918	0.713	1.180	0.502
CD14pt
Right	34 (63.0)	1.075	0.891	1.297	0.449		1.790	0.592	5.406	0.302
Left	20 (37.0)	1.472	1.095	1.978	0.010	< 0.05
LMRt
Right	34 (63.0)	0.555	0.337	0.915	0.021	< 0.05	0.641	0.213	1.926	0.428
Left	20 (37.0)	1.084	0.999	1.176	0.052		0.165	0.003	9.203	0.380
LMRpt
Right	34 (63.0)	0.691	0.458	1.042	0.078		0.312	0.123	0.793	0.014	< 0.05
Left	20 (37.0)	1.066	0.688	1.653	0.775
CD4MRt
Right	34 (63.0)	0.588	0.220	1.572	0.290		0.876	0.382	2.010	0.756
Left	20 (37.0)	0.950	0.381	2.370	0.912
CD4MRpt
Right	34 (63.0)	0.734	0.327	1.648	0.454		7.229	0.515	101.544	0.142
Left	20 (37.0)	0.583	0.199	1.709	0.325
CD8MRt
Right	34 (63.0)	0.497	0.246	1.005	0.052
Left	20 (37.0)	1.083	0.999	1.174	0.052		1.123	1.020	1.238	0.019	< 0.05
CD8MRpt
Right	34 (63.0)	0.584	0.333	1.023	0.060
Left	20 (37.0)	1.191	0.815	1.741	0.365		0.293	0.026	3.345	0.323
LMRb/LMRt
Right	34 (63.0)	1.311	1.013	1.697	0.040	< 0.05
Left	20 (37.0)	0.958	0.730	1.258	0.760
LMRb/LMRpt
Right	34 (63.0)	1.248	0.887	1.756	0.203		0.404	0.169	0.969	0.042	< 0.05
Left	20 (37.0)	1.030	0.787	1.347	0.830		1.132	0.859	1.493	0.378
LMRb/CD4MRt
Right	34 (63.0)	1.012	0.965	1.060	0.632		1.056	0.973	1.146	0.192
Left	20 (37.0)	0.991	0.937	1.048	0.742
LMRb/CD4MRpt
Right	34 (63.0)	1.031	0.948	1.121	0.479		1.393	0.875	2.220	0.163
Left	20 (37.0)	1.023	0.969	1.079	0.412		0.925	0.847	1.011	0.087
LMRb/CD8MRt
Right	34 (63.0)	1.146	1.017	1.292	0.025	< 0.05	1.301	1.078	1.571	0.006	< 0.01
Left	20 (37.0)	0.941	0.775	1.143	0.542		1.036	0.591	1.816	0.903
LMRb/CD8MRpt
Right	34 (63.0)	1.022	0.894	1.169	0.746		1.390	0.304	6.350	0.671
Left	20 (37.0)	0.968	0.844	1.109	0.638		0.847	0.576	1.244	0.397

LMR: Lymphocyte-to-monocyte ratio; NLR: Neutrophil-to-lymphocytes ratio; PLR: Platelet-to-lymphocyte ratio; HR: Hazard ratio; CI: Confidence interval; b: Blood; t: Tumour; pt: Peritumour; CD4MR: CD4⁺-lymphocyte-to-monocyte ratio; CD8MR: CD8⁺-lymphocyte-to-monocyte ratio.