Exploring macrophage polarization as a prognostic indicator for colorectal cancer: Unveiling the impact of metalloproteinase mutations

Table 1 Variable analysis regarding microsatellite instability (n = 61)

	Total		No mutation, n = 33		With mutation, n = 28		P value
	n	%	n	%	n	%
Age (year)							0.1351
≤ 60	15	24.6	11	33.3	4	14.3
> 60	46	75.4	22	66.7	24	85.7
Sex							0.0931
Female	43	70.5	20	60.6	23	82.1
Male	18	29.5	13	39.4	5	17.9
Location							0.1541
Right colon	44	72.1	21	54.5	23	78.6
Left colon	17	27.9	12	45.5	5	21.4
Staging							0.051
I	10	16.9	3	9.7	7	25.0
II	19	32.2	7	22.6	12	42.9
III	25	42.4	18	58.0	7	25
IV	5	8.5	3	9.7	2	7.1
Colectomy							0.248
Right side	39	63.9	18	54.5	21	75.0
Left side	15	24.6	10	30.3	5	17.9
Total	7	11.5	5	15.2	2	7.1
Lymphocytes							0.24
Low	30	50.0	18	54.6	12	44.4
Moderate	18	30.0	7	21.2	11	40.7
Intense	12	20.0	8	24.2	4	14.9
Reccurence							0.4431
No	49	87.5	26	83.9	23	92.0
Yes	7	12.5	5	16.1	2	8.0
Clinical outcome							1.01
Disease-free	49	80.3	26	78.8	23	82.1
Death	12	19.7	7	21.2	5	17.9

¹P values obtained via Fisher's exact test.

Table 2 Variable analysis regarding staging (n = 61)

	Total		Stage I, n = 10		Stage II, n = 19		Stage III, n = 25		Stage IV, n = 5		P value
	n	%	n	%	n	%	n	%	n	%
Instability											0.05a
No mutation	33	52.5	3	30.0	8	40.0	18	72.0	4	66.66
With mutation	28	47.5	7	70.0	12	60.0	7	28.0	2	33.33
Age (year)											0.61
≤ 60	15	24.6	1	10.0	6	30.0	7	28.0	1	16.7
> 60	46	75.4	9	90.0	14	70.0	18	72.0	5	83.3
Sex											0.055
Female	43	70.5	9	90.0	17	85.0	14	56.0	3	50.0
Male	18	29.5	1	10.0	3	15.0	11	44.0	3	50.0
Location											0.722
Right colon	44	72.1	8	80.0	16	80.0	17	68.0	3	50.0
Left colon	17	27.9	2	20.0	4	20.0	8	32.0	3	50.0
Colectomy											0.342
Right side	39	63.9	7	70.0	15	75.0	14	56.0	3	50.0
Left side	15	24.6	3	30.0	3	15.0	6	24.0	3	50.0
Total	7	11.5	0	0.0	2	10.0	5	20.0	0	0.0
Lymphocytes											0.874
Low	30	50.0	3	33.3	10	50.0	14	56.0	3	50.0
Moderate	18	30.0	4	44.4	6	30.0	7	28.0	1	16.6
Intense	12	20.0	2	22.2	4	20.0	4	16.0	2	33.3
Recurrence											0.59
No	49	87.5	9	100.0	16	89.0	19	82.6	5	83.3
Yes	7	12.5	0	0.0	2	11.0	4	17.4	1	16.7
Clinical outcome											0.022a
Disease-free	49	80.3	8	80.0	17	85.0	22	88.0	2	33.3
Death	12	19.7	1	10.0	3	15.0	3	12.0	4	66.6

^aStatistically significant.

Qualitative variables expressed in values of absolute frequency and relative frequency.

The percentual value shown as relative frequency is taking into account the percentage of valid cases, that is, excluding the missing values.

Table 3 Factorial analysis of macrophages regarding tumor location (n = 61)

		n	%	mean ± SD	P value
CD68					0.757
Right side	No mutation	21	47.7	31.667 ± 25.997
	With mutation	23	52.3	30.0 ± 25.849
Left side	No mutation	12	70.6	33.75 ± 28.534
	With mutation	5	29.4	37.2 ± 32.042
CD163					0.256
Right side	No mutation	21	47.7	23.881 ± 20.987
	With mutation	23	52.3	20.109 ± 19.934
Left side	No mutation	12	70.6	21.750 ± 24.076
	With mutation	5	29.4	33.3 ± 28.504
CD206					0.117
Right side	No mutation	21	47.7	19.057 ± 19.358
	With mutation	23	52.3	14.226 ± 15.599
Left side	No mutation	12	70.6	15.458 ± 12.648
	With mutation	5	29.4	27.4 ± 23.954
iNOS					0.179
Right side	No mutation	21	47.7	6.767 ± 13.487
	With mutation	23	52.3	3.57 ± 4.831
Left side	No mutation	12	70.6	3.383 ± 4.522
	With mutation	5	29.4	8.21 ± 15.199

Table 4 MANOVA analysis of macrophages CD163, iNOS e CD206 combined (n = 61)

	Degrees of freedom	F	Hotelling-Lawley test	P value
Instability	1	0.314	0.005	0.958
Age	1	0.537	0.028	0.659
Location	1	0.058	0.003	0.936
Staging	3	1.697	0.296	0.094
Recurrence	1	0.650	0.038	0.586
Clinical outcome	1	1.929	0.102	0.305
Instability vs location	1	1.061	0.006	0.322
Instability vs clinical outcome	1	2.592	0.141	0.019

Table 5 Macrophage evaluation (n = 61)

	Total		CD68		CD163		iNOS		CD206
	n	%	mean ± SD	P value	mean ± SD	P value	mean ± SD	P value	mean ± SD	P value
Instability				0.753		0.868		0.524		0.690
No mutation	33	54.1	32.424 ± 26.52		23.106 ± 21.809		5.536 ± 11.11		17.748 ± 17.097
With mutation	28	45.9	31.286 ± 26.541		22.464 ± 21.694		4.398 ± 7.518		16.579 ± 17.598
Age (year)				0.483		0.706		0.993		0.251
≤ 60	15	24.6	33.0 ± 21.696		22.5 ± 17.687		5.377 ± 9.082		20.067 ± 15.374
> 60	46	75.4	31.543 ± 27.861		22.913 ± 22.877		4.896 ± 9.819		16.280 ± 17.804
Sex				0.295		0.496		0.701		0.275
Female	43	70.5	33.953 ± 26.403		23.919 ± 21.043		4.526 ± 6.575		19.191 ± 18.764
Male	18	29.5	27.0 ± 26.183		20.167 ± 23.208		6.181 ± 14.644		12.483 ± 11.825
Location				0.77		0.923		0.332		0.551
Right colon	44	72.1	30.795 ± 25.63		21.909 ± 20.293		5.095 ± 4.803		16.532 ± 17.457
Left colon	17	27.9	34.765 ± 28.619		25.147 ± 25.121		4.803 ± 8.772		18.971 ± 16.879
Staging				0.371		0.454		0.402		0.973
I	10	16.9	24.5 ± 21.141		15.65 ± 15.431		5.06 ± 6.184		16.1 ± 15.911
II	19	32.2	37.368 ± 25.732		24.079 ± 21.545		6.029 ± 8.282		18.684 ± 17.811
III	25	42.4	28.84 ± 26.226		22.42 ± 22.71		2.868 ± 3.554		17.808 ± 19.248
IV	5	8.5	43.0 ± 38.987		34.4 ± 28.369		12.8 ± 28.066		10.94 ± 8.029
Colectomy				0.93		0.994		0.59		0.634
Right side	39	63.9	31.026 ± 26.462		22.474 ± 20.703		4.954 ± 10.326		18.069 ± 17.915
Left side	15	24.6	33.4 ± 28.306		23.567 ± 24.243		3.777 ± 5.634		16.033 ± 14.502
Total	7	11.5	33.571 ± 24.616		23.071 ± 23.816		8.0 ± 12.342		14.957 ± 20.454
Lymphocytes				0.636		0.593		0.544		0.417
Low	30	50.0	33.867 ± 28.295		36.25 ± 27.89		6.555 ± 11.843		16.033 ± 16.511
Moderate	18	30.0	26.944 ± 22.37		22.567 ± 23.103		2.339 ± 3.0		15.261 ± 15.029
Intense	12	20.0	36.25 ± 27.89		21.306 ± 20.569		5.583 ± 9.758		24.1 ± 21.661
Recurrence				0.499		0.719		0.388		0.941
No	49	87.5	33.98 ± 26.279		24.337 ± 22.125		5.637 ± 10.421		17.518 ± 16.553
Yes	7	12.5	30.714 ± 31.282		22.929 ± 22.606		2.507 ± 3.446		22.286 ± 25.063
Clinical outcome				0.252		0.429		0.208		0.167
Disease-free	49	80.3	30.261 ± 25.51		23.378 ± 21.317		4.578 ± 6.32		10.392 ± 9.601
Death	12	19.7	27.917 ± 30.261		20.5 ± 23.434		6.796 ± 17.917		18.882 ± 18.273

Table 6 Variable analysis regarding grouping results (n = 61)

	Group 1, n = 19	Group 2, n = 42	P value
CD 68	64.737 ± 17.048	17.048 ± 12.61	< 0.01
CD163	50.053 ± 10.488	15.29 ± 8.897	< 0.01
iNOS	9.474 ± 15.19	2.996 ± 4.389	0.064
CD 206	38.211 ± 14.635	7.712 ± 6.462	< 0.01
Age (complete years)	64.947 ± 11.038	66.405 ± 12.655	0.548
Time to death (days)	161.333 ± 238.123	421.875 ± 391.745	0.279

Quantitative variables expressed in values of mean ± SD.

Table 7 Analysis of correlation between variables of macrophage measurement (n = 61)

Comparison	Rho	P value
CD68c CD163	0.897	< 0.001a
CD68c iNOS	0.556	< 0.001a
CD68c CD206	0.783	< 0.001a
CD68c age	-0.155	0.233
CD163c iNOS	0.466	< 0.001a
CD163c CD206	0.796	< 0.001a
CD163c age	-0.156	0.229
iNOSc CD206	0.383	0.002b
iNOSc age	-0.206	0.112
CD206c age	-0.233	0.07

^aP < 0.001.

^bP < 0.01.

^cP < 0.05.

Table 8 Analysis of variables regarding grouping results (n = 61)

	Total		Group 1, n = 19		Group 2, n = 42		P value
	n	%	n	%	n	%
Instability							0.785a
No mutation	33	52.5	11	57.9	22	52.4
With mutation	28	47.5	8	42.1	20	47.6
Age (year)							1.0a
≤ 60	15	24.6	5	26.3	10	23.8
> 60	46	75.4	14	73.7	32	76.2
Sex							0.14a
Female	43	70.5	16	84.2	27	64.3
Male	18	29.5	3	15.8	15	35.71
Location							0.76a
Right colon	44	72.1	13	68.4	31	73.8
Left colon	17	27.9	6	31.6	11	26.2
Staging							0.96
I	10	16.9	3	16.7	7	17.1
II	19	32.2	6	33.3	13	31.7
III	25	42.4	7	38.9	18	43.9
IV	5	8.5	2	11.1	3	7.3
Colectomy							0.592
Right side	39	63.9	13	68.4	26	61.9
Left side	15	24.6	5	26.3	10	23.8
Total	7	11.5	1	5.3	6	14.3
Lymphocytes							0.91
Low	30	50.0	18	54.6	12	44.4
Moderate	18	30.0	7	21.2	11	40.7
Intense	12	20.0	8	24.2	4	14.9
Recurrence							0.679a
No	49	87.5	16	84.2	33	78.5
Yes	7	12.5	3	15.8	4	9.5
Clinical Outcome							0.737a
Disease-free	50	82.0	16	84.2	34	81.0
Death	11	18.0	3	15.8	8	19.0

^aP values obtained via Fisher's exact test.