Expression and clinical significance of STRA6, CYP24A1, and NXPH4 in colorectal cancer liver metastasis

doi:10.3877/cma.j.issn.2095-3224.2026.01.006

Abstract

Abstract:

Objective

This study aimed to investigate the expression of stimulated by retinoic acid 6(STRA6), cytochrome P450 family 24 subfamily A member 1(CYP24A1), and neurexophilin 4(NXPH4) proteins in colorectal cancer liver metastasis and their correlations with clinicopathological characteristics, prognosis, and diagnostic significance.

Methods

A total of 80 patients with colorectal cancer initially diagnosed and undergoing surgery at the First Affiliated Hospital of Hebei North University between January 2017 and December 2019 were enrolled. Among them, thirty patients developed liver metastasis, while 50 did not. Immunohistochemistry was used to detect the expression levels of STRA6, CYP24A1, and NXPH4. The relationships between these proteins and clinicopathological parameters were analyzed. The Kaplan-Meier method was applied to evaluate the prognostic significance of these proteins in colorectal liver metastasis patients. Univariate and multivariate logistic regression analyses were conducted to identify influencing factors for liver metastasis in colorectal cancer patients. Receiver operating characteristic (ROC) curve analysis was utilized to assess the predictive value of individual and combined detection of these proteins for colorectal liver metastasis.

Results

The expression levels of STRA6, CYP24A1, and NXPH4 were significantly higher in the liver metastasis group compared to the non-metastasis and paracancerous tissue groups (P<0.05). In colorectal liver metastasis patients, high expression of STRA6 and NXPH4 was correlated with lymph node metastasis and depth of invasion, while high expression of CYP24A1 was associated with lymph node metastasis, depth of invasion, and tumor differentiation (P<0.05). Survival analysis showed that colorectal liver metastasis patients with high expression of STRA6, CYP24A1, and NXPH4 had a lower 5-year survival rate (HR=2.690, 4.279, and 2.784, respectively; P<0.05). Liver metastasis in colorectal cancer patients was correlated with lymph node metastasis, depth of invasion, and degree of differentiation, and CEA (P<0.05). Multivariate analysis identified lymph node metastasis, CEA≥5 ng/mL, and elevated levels of STRA6, CYP24A1, and NXPH4 as independent risk factors for liver metastasis (P<0.05). ROC curve analysis demonstrated that the AUC values for predicting colorectal liver metastasis were 0.722 (95%CI: 0.602~0.843) for STRA6, 0.797 (95%CI: 0.696~0.898) for CYP24A1, and 0.696 (95%CI: 0.577~0.814) for NXPH4. The sensitivities and specificities were 46.70% and 94.00% for STRA6, 56.70% and 92.00% for CYP24A1, and 86.70% and 52.00% for NXPH4, respectively. The combined detection of these proteins achieved an AUC of 0.820 (95%CI: 0.719~0.921), with a sensitivity of 66.70% and specificity of 90.00%.

Conclusion

High expression of STRA6, CYP24A1, and NXPH4 indicates an increased risk of liver metastasis and poor prognosis in colorectal cancer patients. These proteins may serve as potential biomarkers for risk stratification and prognosis of colorectal cancer liver metastasis, providing references for early clinical intervention.

Key words: Colorectal cancer, Livermetastases, Clinicopathological features, Prognostic analysis

Ziqing Yu, Duo Li, Huan Wang, Xueliang Wu, Jianchun Fan, Xiao Han. Expression and clinical significance of STRA6, CYP24A1, and NXPH4 in colorectal cancer liver metastasis[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2026, 15(01): 58-66.

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References 23

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组别	STRA6平均光密度	CYP24A1平均光密度	NXPH4平均光密度
癌旁组（n=80）	0.122±0.033	0.120±0.028	0.137±0.030
结直肠癌未转移组（n=50）	0.140±0.028	0.143±0.047	0.182±0.045
结直肠癌肝转移组（n=30）	0.175±0.051	0.218±0.078	0.218±0.055
F值	20.273	36.704	35.971
P值	<0.001	<0.001	<0.001

组别	STRA6平均光密度	CYP24A1平均光密度	NXPH4平均光密度
癌旁组（n=80）	0.122±0.033	0.120±0.028	0.137±0.030
结直肠癌未转移组（n=50）	0.140±0.028	0.143±0.047	0.182±0.045
结直肠癌肝转移组（n=30）	0.175±0.051	0.218±0.078	0.218±0.055
F值	20.273	36.704	35.971
P值	<0.001	<0.001	<0.001

临床病理因素	例数	STRA6			CYP24A1			NXPH4
临床病理因素	例数	平均光密度值	t值	P值	平均光密度值	t值	P值	平均光密度值	t值	P值
年龄（岁）			−1.469	0.153		−0.588	0.561		−1.233	0.228
≤60	14	0.189±0.057			0.227±0.079			0.231±0.052
>60	16	0.162±0.042			0.210±0.078			0.207±0.056
性别			−0.822	0.418		0.868	0.622		−0.464	0.646
男性	17	0.182±0.052			0.212±0.077			0.222±0.056
女性	13	0.166±0.050			0.226±0.080			0.213±0.055
浸润深度			3.317	0.003		2.421	0.022		0.159	0.014
T₁~T₂	14	0.147±0.045			0.184±0.081			0.192±0.044
T₃~T₄	16	0.200±0.043			0.248±0.062			0.241±0.055
淋巴结转移			2.487	0.019		2.435	0.022		3.244	0.003
有	21	0.189±0.053			0.239±0.080			0.237±0.054
无	9	0.143±0.026			0.169±0.045			0.175±0.029
肿瘤分化程度			1.166	0.253		2.406	0.023		1.257	0.219
中-高分化	10	0.160±0.044			0.174±0.071			0.201±0.032
低分化	20	0.183±0.053			0.240±0.072			0.227±0.062
原发肿瘤直径（cm）			1.108	0.277		0.031	0.975		0.943	0.354
<5	19	0.167±0.036			0.218±0.078			0.211±0.052
≥5	11	0.188±0.069			0.219±0.080			0.231±0.061
CEA（ng/mL）			−0.457	0.652		−1.614	0.118		−1.559	0.130
<5	5	0.165±0.021			0.168±0.049			0.184±0.033
≥5	25	0.177±0.055			0.228±0.079			0.225±0.056
CA19-9（U/mL）			−1.821	0.079		−0.286	0.777		−1.134	0.266
<35	11	0.154±0.039			0.213±0.089			0.203±0.050
≥35	19	0.187±0.053			0.221±0.073			0.227±0.057

临床病理因素	例数	STRA6			CYP24A1			NXPH4
临床病理因素	例数	平均光密度值	t值	P值	平均光密度值	t值	P值	平均光密度值	t值	P值
年龄（岁）			−1.469	0.153		−0.588	0.561		−1.233	0.228
≤60	14	0.189±0.057			0.227±0.079			0.231±0.052
>60	16	0.162±0.042			0.210±0.078			0.207±0.056
性别			−0.822	0.418		0.868	0.622		−0.464	0.646
男性	17	0.182±0.052			0.212±0.077			0.222±0.056
女性	13	0.166±0.050			0.226±0.080			0.213±0.055
浸润深度			3.317	0.003		2.421	0.022		0.159	0.014
T₁~T₂	14	0.147±0.045			0.184±0.081			0.192±0.044
T₃~T₄	16	0.200±0.043			0.248±0.062			0.241±0.055
淋巴结转移			2.487	0.019		2.435	0.022		3.244	0.003
有	21	0.189±0.053			0.239±0.080			0.237±0.054
无	9	0.143±0.026			0.169±0.045			0.175±0.029
肿瘤分化程度			1.166	0.253		2.406	0.023		1.257	0.219
中-高分化	10	0.160±0.044			0.174±0.071			0.201±0.032
低分化	20	0.183±0.053			0.240±0.072			0.227±0.062
原发肿瘤直径（cm）			1.108	0.277		0.031	0.975		0.943	0.354
<5	19	0.167±0.036			0.218±0.078			0.211±0.052
≥5	11	0.188±0.069			0.219±0.080			0.231±0.061
CEA（ng/mL）			−0.457	0.652		−1.614	0.118		−1.559	0.130
<5	5	0.165±0.021			0.168±0.049			0.184±0.033
≥5	25	0.177±0.055			0.228±0.079			0.225±0.056
CA19-9（U/mL）			−1.821	0.079		−0.286	0.777		−1.134	0.266
<35	11	0.154±0.039			0.213±0.089			0.203±0.050
≥35	19	0.187±0.053			0.221±0.073			0.227±0.057

影响因素	结直肠癌未转移组（n=50）	结直肠癌肝转移组（n=30）	χ^²值	P值
年龄（岁）			0.166	0.684
≤60	21（42.0）	14（46.7）
>60	29（58.0）	16（53.3）
性别			0.054	0.816
男性	27（54.0）	17（56.7）
女性	23（46.0）	13（43.3）
浸润深度			4.301	0.038
T₁~T₂	35（70.0）	14（46.7）
T₃~T₄	15（30.0）	16（53.3）
淋巴结转移			9.744	0.002
有	17（34.0）	21（70.0）
无	33（66.0）	9（30.0）
肿瘤分化程度			4.566	0.033
中-高分化	29（58.0）	10（33.3）
低分化	21（42.0）	20（66.7）
原发肿瘤直径（cm）			1.469	0.226
<5	38（76.0）	19（63.3）
≥5	12（24.0）	11（36.7）
CEA（ng/mL）			4.752	0.029
<5	20（40.0）	5（16.7）
≥5	30（60.0）	25（83.3）
CA19-9（U/mL）			0.979	0.323
<35	24（48.0）	11（36.7）
≥35	26（52.0）	19（63.3）

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