Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients

doi:10.4240/wjgs.v13.i7.689

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World Journal of Gastrointestinal Surgery

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Retrospective Study

World J Gastrointest Surg. Jul 27, 2021; 13(7): 689-701
Published online Jul 27, 2021. doi: 10.4240/wjgs.v13.i7.689

Table 1 Baseline patient clinicopathologic characteristics

		Progression-free survival		¹P value	Overall survival		¹P value
		No progression	Progression		Survival	Death
		(n = 1388) (%)	(n = 308) (%)		(n = 1494) (%)	(n = 202) (%)
Age (yr) (mean ± SD)		58.61 ± 11.71	58.48 ± 12.64	0.861	58.64 ± 11.75	58.19 ± 12.81	0.618
Sex	Male	821 (59.15)	195 (63.31)	0.199	880 (58.90)	136 (67.33)	0.022
Sex	Female	567 (40.85)	113 (36.69)	0.199	614 (41.10)	66 (32.67)	0.022
Tumor location	Colon	801 (57.71)	178 (57.79)	0.999	861 (57.63)	118 (58.42)	0.880
Tumor location	Rectum	587 (42.29)	130 (42.21)	0.999	633 (42.37)	84 (41.58)	0.880
TNM stage	I	216 (15.56)	7 (2.27)	< 0.001	219 (14.66)	4 (1.98)	< 0.001
	II	522 (37.61)	51 (16.56)		536 (35.88)	37 (18.32)
	III	561 (40.42)	93 (30.19)		570 (38.15)	84 (41.58)
	IV	89 (6.41)	157 (50.97)		169 (11.31)	77 (38.12)
Tumor size (cm)	d < 2	61 (4.39)	12 (3.90)	0.863	67 (4.48)	6 (2.97)	0.246
	2 ≤ d < 5	886 (63.83)	201 (65.26)		964 (64.52)	123 (60.89)
	d > 5	441 (31.77)	95 (30.84)		463 (31.00)	73 (36.14)
Differentiation	Low	186 (13.40)	36 (11.69)	0.586	192 (12.85)	30 (14.85)	0.648
	Medium	1104 (79.54)	253 (82.14)		1197 (80.12)	160 (79.21)
	High	98 (7.06)	19 (6.17)		105 (7.03)	12 (5.94)
Circumferential margin	No	1372 (98.85)	301 (97.73)	0.167	1477 (98.86)	196 (97.03)	0.047
Circumferential margin	Yes	16 (1.15)	7 (2.27)	0.167	17 (1.14)	6 (2.97)	0.047
Vascular tumor thrombus	No	1111 (80.04)	218 (70.78)	0.001	1180 (78.98)	149 (73.76)	0.101
Vascular tumor thrombus	Yes	277 (19.96)	90 (29.22)	0.001	314 (21.02)	53 (26.24)	0.101
Nerve invasion	No	1098 (79.11)	228 (74.03)	0.057	1177 (78.78)	149 (73.76)	0.122
Nerve invasion	Yes	290 (20.89)	80 (25.97)	0.057	317 (21.22)	53 (26.24)	0.122
Chemotherapy	No	606 (43.66)	87 (28.25)	< 0.001	603 (40.36)	90 (44.55)	0.254
Chemotherapy	Yes	782 (56.34)	221 (71.75)	< 0.001	891 (59.64)	112 (55.45)	0.254
Radiotherapy	No	1315 (94.74)	275 (89.29)	0.001	1400 (93.71)	190 (94.06)	0.999
Radiotherapy	Yes	73 (5.26)	33 (10.71)	0.001	94 (6.29)	12 (5.94)	0.999
ApoA1 (G/L)		1.22 ± 0.25	1.12 ± 0.27	< 0.001	1.20 ± 0.25	1.12 ± 0.28	0.010
ApoB (G/L)		0.94 ± 0.23	0.91 ± 0.24	0.170	0.93 ± 0.23	0.92 ± 0.25	0.628
HDL-C (mmol/L)		1.22 ± 0.33	1.20 ± 0.34	0.208	1.22 ± 0.33	1.20 ± 0.37	0.440
LDL-C (mmol/L)		2.62 ± 0.75	2.60 ± 0.84	0.807	2.61 ± 0.75	2.64 ± 0.90	0.664

¹P value was calculated by the Student’s t-test for continuous variables and the Chi-square test for categorical variables.

ApoA1: Apolipoprotein A1; ApoB: Apolipoprotein B; HDL-C: High-density lipoprotein-cholesterol; TNM: Tumor node metastasis; LDL-C: Low-density lipoprotein-cholesterol.

Table 2 Cox proportional hazards regression analyses for basic lipid indicators for progression-free survival and overall survival

	AUC	Cut-point	PFS
			Univariate	P value	Multivariate¹	P value
			HR (95%CI)	P value	HR (95%CI)	P value
HDL-C (mmol/L)	0.519	0.920	0.699 (0.530-0.920)	0.011^b	0.696 (0.528-0.918)	0.010^a
LDL-C (mmol/L)	0.513	2.160	0.865 (0.679-1.103)	0.242	0.878 (0.689-1.119)	0.295
ApoA1 (G/L)	0.610	1.030	0.520 (0.374-0.725)	< 0.001^b	0.617 (0.442-0.863)	0.005^a
ApoB (G/L)	0.547	0.860	0.743 (0.537-1.029)	0.074	0.796 (0.574-1.103)	0.170
			OS
	AUC	Cut-point	Univariate	P value	Multivariate²	P value
	AUC	Cut-point	HR (95%CI)	P value	HR (95%CI)	P value
HDL-C (mmol/L)	0.519	0.900	0.492 (0.354-0.685)	< 0.001^b	0.505 (0.363-0.702)	< 0.001^a
LDL-C (mmol/L)	0.499	3.650	1.645 (1.096-2.468)	0.016^b	1.503 (1.001-2.258)	0.050
ApoA1 (G/L)	0.578	1.130	0.572 (0.375-0.873)	0.010^b	0.625 (0.410-0.955)	0.030^a
ApoB (G/L)	0.527	0.860	0.744 (0.487-1.136)	0.171	0.807 (0.528-1.234)	0.323

Binary classification (I/II vs III/IV) of tumor node metastasis (TNM) stage was adopted.

¹(Progression-free survival) Multivariate analysis adjusted for age, TNM stage, vascular tumor thrombus, chemotherapy, and radiotherapy. We used a stepwise regression approach for multivariate analysis.

²(Overall survival) Multivariate analysis adjusted for age, sex, TNM stage, and circumferential margin.

^aStatistical significance is expressed as P < 0.05 (for multivariate analysis).

^bStatistical significance is expressed as P < 0.05 (for univariate analysis).

HR: Hazard ratio; 95%CI: 95% confidence interval; AUC: Area under the ROC curve; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; ApoA1: Apolipoprotein A1; ApoB: Apolipoprotein B; TNM: Tumor node metastasis; PFS: Progression-free survival; OS: Overall survival.

Table 3 Cox proportional hazards regression analyses for lipid-based indicators for progression-free survival and overall survival

	AUC	Cut-point	PFS
			Univariate	P value	Multivariate¹	P value
			HR (95%CI)	P value	HR (95%CI)	P value
HDL-C/LDL-C	0.497	0.323	0.672 (0.500-0.904)	0.009^b	0.710 (0.528-0.955)	0.024^a
ApoA1/ApoB	0.528	0.909	0.465 (0.302-0.715)	0.001^b	0.501 (0.324-0.775)	0.002^a
			OS
	AUC	Cut-point	Univariate	P value	Multivariate²	P value
	AUC	Cut-point	HR (95%CI)	P value	HR (95%CI)	P value
HDL-C/LDL-C	0.506	0.323	0.573 (0.402-0.815)	0.002^b	0.619 (0.434-0.882)	0.008^a
ApoA1/ApoB	0.527	0.871	0.411 (0.232-0.729)	0.002^b	0.481 (0.271-0.853)	0.012^a

Binary classification (I/II vs III/IV) of tumor node metastasis (TNM) stage was adopted.

²(Overall survival) Multivariate analysis adjusted for age, sex, TNM stage, and circumferential margin.

^aStatistical significance is expressed as P < 0.05 (for multivariate analysis).

^bStatistical significance is expressed as P <0.05 (for univariate analysis).

HR: Hazard ratio; 95%CI: 95% confidence interval; AUC: Area under the ROC Curve; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; ApoA1: Apolipoprotein A1; ApoB: Apolipoprotein B; PFS: Progression-free survival; OS: Overall survival.

Table 4 Cox proportional hazards regression analyses for lipoprotein-cholesterol-apolipoprotein score for progression-free survival and overall survival

	Continuous variable
	PFS
	Univariate	P value	Multivariate¹	P value
	HR (95%CI)	P value	HR (95%CI)	P value
LA score³	0.625 (0.490-0.797)	< 0.001^b	0.654 (0.512-0.836)	0.001^a
	OS
	Univariate	P value	Multivariate²	P value
	HR (95%CI)	P value	HR (95%CI)	P value
LA score³	0.616 (0.453-0.838)	0.002^b	0.677 (0.500-0.917)	0.012^a
	Dummy variable
	PFS
	Univariate	P value	Multivariate¹	P value
	HR (95%CI)	P value	HR (95%CI)	P value
LA score³ 1	0.598 (0.280-1.277)	0.184	0.646 (0.302-1.383)	0.261
LA score³ 2	0.387 (0.233-0.643)	< 0.001^b	0.427 (0.256-0.713)	0.001^a
	OS
	Univariate	P value	Multivariate²	P value
	HR (95%CI)	P value	HR (95%CI)	P value
LA score³ 1	0.973 (0.370-2.561)	0.956	1.508 (0.507-3.992)	0.408
LA score³ 2	0.413 (0.213-0.802)	0.009^b	0.524 (0.269-1.019)	0.057

Binary classification (I/II vs III/IV) of tumor node metastasis (TNM) stage was adopted.

²(Overall survival) Multivariate analysis adjusted for age, sex, TNM stage, and circumferential margin.

³This indicator combined ApoA1/ApoB and HDL-C/LDL-C. Per additional score was associated with a decreased risk of progression-free survival and overall survival in colorectal cancer patient.

^aStatistical significance is expressed as P < 0.05 (for multivariate analysis).

^bStatistical significance is expressed as P < 0.05 (for univariate analysis).

HR: Hazard ratio; 95%CI: 95% confidence interval; AUC: Area under the ROC curve; PFS: Progression-free survival; OS: Overall survival; LA: Lipoprotein cholesterol-apolipoprotein.

Table 5 Association between lipoprotein-cholesterol-apolipoprotein score with overall survival and progression-free survival in patients with colorectal cancer among different subgroups

		LA score
		PFS			OS
		n	Progression	HR (95%CI)	n	Death	HR (95%CI)
Age (yr)	< 65	330	90	0.725 (0.532-0.987)	330	49	0.626 (0.424-0.924)
Age (yr)	≥ 65	191	58	0.540 (0.358-0.814)	191	38	0.724 (0.437-1.199)
Sex	Male	321	97	0.671 (0.500-0.901)	321	58	0.756 (0.520-1.101)
Sex	Female	200	51	0.592 (0.366-0.956)	200	29	0.572 (0.333-0.981)
TNM stage	I/II	243	35	0.805 (0.421-1.538)	243	15	0.678 (0.265-1.735)
TNM stage	III/IV	278	113	0.632 (0.485-0.824)	278	72	0.676 (0.490-0.932)
Tumor location	Colon	320	91	0.793 (0.557-1.128)	320	53	0.686 (0.454-1.036)
Tumor location	Rectum	201	57	0.582 (0.411-0.826)	201	34	0.710 (0.450-1.121)
Tumor size (cm)	d < 2	12	2	0	12	2	0
	2 ≤ d < 5	374	108	0.575 (0.435-0.761)	374	61	0.636 (0.445-0.908)
	d ≥ 5	135	38	0.792 (0.485-1.294)	135	24	0.634 (0.354-1.137)
Differentiation	Low	56	18	0.504 (0.286-0.890)	56	11	0.298 (0.149-0.594)
	Medium	415	118	0.722 (0.534-0.977)	415	68	0.781 (0.528-1.155)
	High	50	12	0.534 (0.261-1.093)	50	8	0.704 (0.313-1.586)

LA: Lipoprotein cholesterol-apolipoprotein; PFS: Progression-free survival; OS: Overall survival; HR: Hazard Ratio; CI: Confidence interval.

Citation: Gu JN, Yao S, Cao YH, Deng SH, Mao FW, Jiang HY, He YT, Li XY, Ke SQ, Li HL, Li H, Liu XH, Liu HL, Wang JL, Wu K, Liu L, Cai KL. Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients. World J Gastrointest Surg 2021; 13(7): 689-701
URL: https://www.wjgnet.com/1948-9366/full/v13/i7/689.htm
DOI: https://dx.doi.org/10.4240/wjgs.v13.i7.689