Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage II/III colorectal cancer: Cancer progression and prognosis

doi:10.3748/wjg.v26.i43.6853

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastroenterol. Nov 21, 2020; 26(43): 6853-6866
Published online Nov 21, 2020. doi: 10.3748/wjg.v26.i43.6853

Table 1 Correlation of immunoreactivity of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 with clinicopathological features

Clinicopathologic characteristics	n (%)	DCLK1		P value	Lgr5		P value
Clinicopathologic characteristics	n (%)	Low (n = 48)	High (n = 44)	P value	Low (n = 62)	High (n = 30)	P value
Age (yr)
≤ 49	49 (53)	26 (53)	23 (47)	0.856	33 (67)	16 (33)	0.992
> 49	43 (47)	22 (51)	21 (49)		29 (67)	14 (33)
Gender
Male	52 (57)	29 (56)	23 (44)	0.431	37 (71)	15 (29)	0.380
Female	40 (43)	19 (47)	21 (53)		25 (63)	15 (37)
Depth of penetration
T3	18 (20)	6 (33)	12 (67)	0.074	13 (72)	5 (28)	0.626
T4	74 (80)	42 (57)	32 (43)		49 (66)	25 (34)
Lymph node
N0	38 (41)	20 (53)	18 (47)	0.892	27 (71)	11 (29)	0.787
N1	41 (45)	22 (54)	19 (46)		27 (66)	14 (34)
N2	13 (14)	6 (12)	7 (16)		8 (62)	5 (38)
Tumor stage (TNM)
II	38 (41)	20 (55)	18 (45)	0.941	27 (71)	11 (29)	0.530
III	54 (59)	28 (52)	26 (48)		35 (65)	19 (35)
Differentiation
Well/moderate	66 (72)	37 (56)	29 (44)	0.234	48 (73)	18 (27)	0.082
Poor/mucinous	26 (28)	11 (42)	15 (58)		14 (54)	12 (46)
Tumor site
Left	42 (46)	24 (57)	18 (43)	0.537	32 (76)	10 (24)	0.032
Right	17 (18)	7 (41)	10 (59)		7 (41)	10 (59)
Rectum	33 (36)	17 (52)	16 (48)		23 (70)	10 (30)
Postoperative adjuvant chemotherapy
Xeloda monotherapy	7 (7)	4 (57)	3 (43)	0.783	5 (71)	2 (29)	0.763
FOLFOX regimen	32 (35)	18 (56)	14 (44)		20 (63)	12 (37)
XELOX regimen	53 (58)	26 (49)	27 (51)		37 (70)	16 (30)
CEA
Normal	68 (74)	38 (56)	30 (44)	0.231	45 (66)	23 (34)	0.676
High	24 (26)	10 (42)	14 (58)		17 (71)	7 (29)
CA19-9
Normal	66 (72)	35 (53)	31 (47)	0.793	45 (68)	21 (32)	0.797
High	26 (28)	13 (50)	13 (50)		17 (67)	9 (33)
MSI
MSS	89 (97)	46 (52)	43 (48)	0.609	60 (67)	29 (33)	0.978
MSI	3 (3)	2 (67)	1 (33)		2 (67)	1 (33)
Recurrence
Absent	67 (73)	37 (55)	30 (45)	0.338	44 (66)	23 (34)	0.565
Present	25 (27)	11 (44)	14 (56)		18 (72)	7 (28)
Lung metastasis
Absent	80 (87)	40 (50)	40 (50)	0.281	52 (65)	28 (35)	0.206
Present	12 (13)	8 (67)	4 (33)		10 (83)	2 (17)
Liver metastasis
Absent	83 (90)	42 (51)	41 (49)	0.359	55 (66)	28 (34)	0.484
Present	9 (10)	6 (67)	3 (33)		7 (78)	2 (22)

DCLK1: Doublecortin-like kinase 1; Lgr5: Leucine-rich repeat-containing G-protein-coupled receptor 5; TNM: Tumor-node-metastasis.

Table 2 Correlation of immunoreactivity of doublecortin-like kinase 1/leucine-rich repeat-containing G-protein-coupled receptor 5 with clinicopathological features

Clinicopathologic characteristics	n (%)	DCLK1/Lgr5 phenotypes				P value
Clinicopathologic characteristics	n (%)	DCLK1^Low /Lgr5^Low	DCLK1^Low /Lgr5^High	DCLK1^High /Lgr5^Low	DCLK1^High /Lgr5^High	P value
Age (yr)
≤ 49	49 (53)	23 (47)	3 (6)	10 (20)	13 (27)	0.890
> 49	43 (47)	18 (42)	4 (9)	11 (26)	10 (23)
Gender
Male	52 (57)	25 (48)	4 (8)	12 (23)	11 (21)	0.348
Female	40 (43)	16 (40)	3 (7)	9 (23)	12 (30)
Depth of penetration
T3	18 (20)	5 (28)	1 (6)	8 (44)	4 (22)	0.223
T4	74 (80)	36 (49)	6 (8)	13 (17)	19 (26)
Lymph node
N0	38 (41)	17 (45)	3 (8)	10 (26)	8 (21)	0.858
N1	41 (45)	18 (44)	4 (10)	9 (22)	10 (24)
N2	13 (14)	6 (46)	0 (0)	2 (15)	5 (39)
Tumor stage (TNM)
II	38 (41)	17 (45)	3 (8)	10 (26)	8 (21)	0.774
III	54 (59)	24 (45)	4 (7)	11 (20)	15 (28)
Differentiation
Well/moderate	66 (72)	32 (48)	5 (8)	16 (24)	13 (20)	0.115
Poor/mucinous	26 (28)	9 (35)	2 (8)	5 (19)	10 (38)
Tumour site
Left	42 (46)	22 (52)	2 (5)	10 (24)	8 (19)	0.187
Right	17 (18)	4 (23)	3 (18)	3 (18)	7 (41)
Rectum	33 (36)	15 (46)	2 (6)	8 (24)	8 (24)
Postoperative adjuvant chemotherapy
Xeloda monotherapy	7 (7)	3 (43)	1 (14)	21 (29)	22 (14)	0.875
FOLFOX regimen	32 (35)	15 (47)	3 (9)	5 (16)	9 (28)
XELOX regimen	53 (58)	23 (43)	3 (6)	14 (26)	13 (25)
CEA
Normal	68 (74)	33 (49)	5 (7)	12 (18)	18 (26)	0.238
High	24 (26)	8 (33)	2 (8)	9 (38)	5 (21)
CA19-9
Normal	66 (72)	29 (44)	6 (9)	16 (24)	15 (23)	0.710
High	26 (28)	12 (46)	1 (4)	5 (19)	8 (31)
MSI
MSS	89 (97)	39 (44)	7 (8)	21 (25)	22 (23)	0.713
MSI	3 (3)	2 (67)	0 (0)	0 (0)	1 (33)
Recurrence
Absent	67 (73)	30 (45)	7 (10)	14 (21)	16 (24)	0.374
Present	25 (27)	11 (44)	0 (0)	7 (28)	7 (28)
Lung metastasis
Absent	80 (87)	33 (41)	7 (9)	19 (24)	21 (26)	0.365
Present	12 (13)	8 (66)	0 (0)	2 (17)	2 (17)
Liver metastasis
Absent	83 (90)	35 (42)	7 (9)	20 (24)	2 (25)	0.478
Present	9 (10)	6 (67)	0 (0)	1 (11)	2 (22)

DCLK1: Doublecortin-like kinase 1; Lgr5: Leucine-rich repeat-containing G-protein-coupled receptor 5; TNM: Tumor-node-metastasis.

Table 3 Prognostic value, univariate and multivariate analyses of potential predictor for recurrence

Variables	HR	95%CI	P value
Univariate
Age (≤ 49 vs > 49 yr)	0.742	0.303-1.818	0.515
Gender (Male vs Female)	0.758	0.302-1.901	0.555
Depth of penetration (T3 vs pT4)	1.310	0.383-4.476	0.006
Lymph node
N0	1 (ref)
N1	2.590	0.795-8.439	0.114
N2	7.562	2.189-26.115	0.001
Tumor stage (TNM) (II vs III)	3.610	1.201-10.849	0.022
Differentiation (well/moderate vs poor/mucinous)	2.561	1.058-6.198	0.037
Tumor site
Left	1 (ref)
Right	0.735	0.205-2.636	0.637
Rectum	0.834	0.307-2.263	0.721
CEA (normal vs high)	4.722	1.933-11.535	0.001
CA19-9 (normal vs high)	3.961	1.633-9.606	0.002
MSI (MSS vs MSI)	0.047	0.000-1327.112	0.559
Lung metastasis (absent vs present)	2.325	0.844-6.405	0.103
Liver metastasis (absent vs present)	2.351	0.785-7.038	0.127
DCLK1 (low vs high)	3.958	1.496-10.472	0.006
Lgr5 (low vs high)	2.521	1.025-6.199	0.044
DCLK1/Lgr5 (others¹vs high/high)	3.808	1.471-9.854	0.006
Multivariate
Tumor stage (TNM) (II vs III)	6.846	1.918-24.445	0.003
Differentiation (well/moderate vs poor/mucinous)	1.864	0.699-4.971	0.241
CEA (normal vs high)	4.835	1.651-14.154	0.004
CA19-9 (normal vs high)	4.102	1.529-11.005	0.005
DCLK1 (low vs high)	4.656	1.207-17.956	0.026
Lgr5 (low vs high)	0.764	0.076-7.691	0.819
DCLK1/Lgr5 (others¹vs high/high)	3.429	0.212-55.583	0.386

¹Low/low low/high and high/low. HR: Hazard ratio; CI: Confidence interval; DCLK1: Doublecortin-like kinase 1; Lgr5: Leucine-rich repeat-containing G-protein-coupled receptor 5; TNM: Tumor-node-metastasis.

Table 4 Prognostic value, univariate and multivariate analyses of potential predictor for survival

Variables	HR	95%CI	P value
Univariate
Age (≤ 49 vs > 49 yr)	0.681	0.276-1.684	0.406
Gender (Male vs Female)	0.795	0.316-2.001	0.626
Depth of penetration (T3 vs pT4)	0.772	0.226-2.640	0.680
Lymph node
N0	1 (ref)
N1	2.774	0.839-9.170	0.094
N2	8.899	2.496-31.723	0.001
Tumor stage (TNM) (II vs III)	3.880	1.274-11.871	0.017
Differentiation (well/moderate vs poor/mucinous)	0.376	0.155-0.913	0.031
Tumour site
Left	1 (ref)
Right	0.798	0.221-2.880	0.731
Rectum	0.872	0.319-2.384	0.790
CEA (normal vs high)	0.245	0.101-0.595	0.002
CA19-9 (normal vs high)	3.569	1.477-8.621	0.005
MSI (MSS vs MSI)	0.047	0.000-3055.106	0.588
Recurrence (absent vs present)	8.038	3.070-21.050	0.001
Lung metastasis (absent vs present)	2.141	0.776-5.911	0.142
Liver metastasis (absent vs present)	2.216	0.734-6.689	0.158
DCLK1 (low vs high)	4.167	1.491-11.644	0.006
Lgr5 (low vs high)	2.575	1.030-6.438	0.043
DCLK1/Lgr5 (others¹vs high/high)	3.273	1.297-8.262	0.012
Multivariate
Tumor stage (TNM) (II vs III)	6.087	1.647-22.499	0.007
Differentiation (well/moderate vs poor/mucinous)	2.706	0.989-7.406	0.053
CEA (normal vs high)	4.363	1.346-14.136	0.014
CA19-9 (normal vs high)	1.078	0.362-3.208	0.893
Recurrence (absent vs present)	12.002	3.066-46.988	0.001
DCLK1 (low vs high)	4.272	1.005-18.167	0.049
Lgr5 (low vs high)	7.088	0.582-86.342	0.125
DCLK1/Lgr5 (others¹vs high/high)	0.593	0.039-9.085	0.708

Citation: Kang XL, He LR, Chen YL, Wang SB. Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage II/III colorectal cancer: Cancer progression and prognosis. World J Gastroenterol 2020; 26(43): 6853-6866
URL: https://www.wjgnet.com/1007-9327/full/v26/i43/6853.htm
DOI: https://dx.doi.org/10.3748/wjg.v26.i43.6853