HTR1D作为结直肠癌治疗靶点和预后指标的筛选及鉴定

胡奕炀; 姚刘旭; 李薇薇; 何柳; 李玉红

doi:10.16766/j.cnki.issn.1674-4152.004403

HTR1D作为结直肠癌治疗靶点和预后指标的筛选及鉴定

doi: 10.16766/j.cnki.issn.1674-4152.004403

胡奕炀^{1, 2},
姚刘旭^{1, 2},
李薇薇³,
何柳⁴,
李玉红^5, ,

1.
浙江省人民医院(杭州医学院附属人民医院)麻醉科，浙江杭州 310014
2.
杭州医学院麻醉与围手术期医学研究所，浙江杭州 310014
3.
绍兴市人民医院消化内科，浙江绍兴 312000
4.
绍兴市人民医院医学研究中心
5.
浙江树人大学，树兰国际医学院，树兰(杭州)医院麻醉科，浙江杭州 310014

基金项目:

浙江省医药卫生科技项目 2024KY680

详细信息

通讯作者:
李玉红，E-mail：yuh_li@zju.edu.cn

中图分类号: R735.3 R730.7
计量
- 文章访问数: 14
- HTML全文浏览量: 6
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2025-03-16
- 网络出版日期: 2026-06-02

Identification of HTR1D as a therapeutic target and prognostic indicator for colorectal cancer

HU Yiyang^{1, 2},
YAO Liuxu^{1, 2},
LI Weiwei³,
HE Liu⁴,
LI Yuhong^{5
, ,}

1.
Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China

摘要

摘要: 目的通过生物信息学方法筛选鉴定结直肠癌差异基因，探讨5-羟色胺受体1D(5-HTR1D)在结直肠癌中的作用及价值。方法利用GEO数据集识别结直肠癌和癌旁正常组织中的差异表达基因(DEGs)。建立蛋白质互作网络，鉴定与结直肠癌相关的关键基因。收集结直肠癌及癌旁组织进行免疫组化，对不同的结直肠癌细胞系进行Western blotting验证HTR1D的差异。通过GO和KEGG富集分析探讨与HTR1D相关的信号通路。采用Kaplan-Meier生存分析和多因素Cox回归分析研究HTR1D表达与结直肠癌患者临床病理特征和预后的关系。建立小鼠异种移植模型，体内实验验证HTR1D作为CRC治疗靶点的有效性。结果 HTR1D在结直肠癌组织中表达显著上调，且主要表达于肿瘤细胞胞质中。Western blotting检测证实在结直肠癌中，HTR1D在低分化细胞系中高表达。临床病理分析证实HTR1D的表达与CRC患者的肿瘤大小(P=0.044)、高血压(P=0.039)显著相关。Kaplan-Meier生存分析[(18.9±2.5)月vs. (26.7±1.9)月，P=0.033]和多因素Cox回归分析表明HTR1D的表达是CRC患者预后的影响因素(P=0.019，HR=1.159，95% CI：1.024~1.312)。体内实验显示抑制HTR1D表达可降低肿瘤的质量和体积。结论 HTR1D可作为结直肠癌的治疗靶点和预后指标。
- 结直肠癌 /
- 差异表达基因 /
- 5-羟色胺受体1D /
- 治疗靶点 /
- 预后
Abstract: Objective To screen and identify differential genes in colorectal cancer by bioinformatics, and to explore the role and value of 5-hydroxytryptamine receptor 1D (5-HTR1D) in colorectal cancer. Methods The differentially expressed genes (DEGs) between colorectal cancer and adjacent normal tissues were identified in this study by using GEO data set. Subsequently, a protein-protein interaction network and key genes related to colorectal cancer were established. Tissue samples from colorectal cancer and adjacent tissues were collected for immunohistochemistry, and different colorectal cancer cell lines were subjected to Western blotting to verify the differences of HTR1D. The potential mechanism of HTR1D was discussed by GO and KEGG enrichment analysis. Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to verify the correlation between HTR1D expression and the clinicopathological features and prognosis of patients with colorectal cancer. A mouse xenotransplantation model was established, and the effectiveness of HTR1D as a target for CRC treatment was verified by in vivo experiments. Results The results of the present study demonstrated that the expression of HTR1D was considerably upregulated in CRC tissue, and was principally expressed in the cytoplasm of tumor cells. Western blotting assay was performed to detect HTR1D expression in CRC cell lines: HTR1D was highly expressed in poorly differentiated cell lines. From clinical aspects, HTR1D expression was significantly correlated with tumor size (P=0.044)and hypertension(P=0.039) in CRC. Kaplan-Meier survival analysis [(18.9±2.5) mouths vs. (26.7±1.9) mouths, P=0.033] and multivariate Cox regression analysis indicated that the expression of HTR1D was closely associated with the prognosis of patients (P=0.019, HR=1.159, 95% CI: 1.024-1.312). In vivo experiments demonstrate that the inhibition of HTR1D expression results in a reduction of expression level in a reduction in the mass and volume of tumors. Conclusion HTR1D has been identified as both a viable therapeutic target and a prognostic indicator in colorectal cancer cases.
- Colorectal cancer /
- Differentially expressed genes /
- 5-hydroxytryptamine receptor 1D /
- Therapeutic target /
- Prognosis

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图 1 CRC中差异基因筛选及生物信息学分析

注：A为DEGs火山图，红色代表上调的基因，绿色代表下调的基因。HTR1D: log(FC)=2.297，P=0.048；B为DEGs的KEGG分析；C为DEGs的PPI网络分析；D为HTR1D在CRC细胞中的表达。

Figure 1. Screening of differential genes in CRC and bioinformatics analysis

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图 2 CRC患者HTR1D的免疫组织化学染色(×200)

注：A为HTR1D高表达的癌组织；B为HTR1D高表达的配对癌旁组织；C为HTR1D低表达的癌组织；D为HTR1D低表达的配对癌旁组织。

Figure 2. Immunohistochemical staining of HTR1D in CRC patients (×200)

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图 3 不同HTR1D表达情况CRC患者KM生存分析

注：红色和蓝色分别代表低和高表达组(P=0.033)。

Figure 3. KM survival analysis of CRC patients with different HTR1D expression

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表 1 不同临床病理特征CRC患者HTR1D表达情况比较(例)

Table 1. Comparison of HTR1D expression in CRC patients with different clinicopathological features (cases)

项目	例数	HTR1D高表达 (n=17)	HTR1D低表达 (n=19)	P值^a
性别				0.158
男性	24	9	15
女性	12	8	4
年龄				0.192
>69岁	21	12	9
≤69岁	15	5	10
高血压				0.039
无	22	7	15
有	14	10	4
糖尿病				0.434
无	29	13	16
有	7	4	3
心肺疾病				0.999
无	29	14	15
有	7	3	4
ASA分级				0.629
1	13	6	7
2	15	6	9
3	8	5	3
远处转移				0.999
无	26	12	14
有	10	5	5
CEA				0.335
阳性(≥5 ng/mL)	20	11	9
阴性(< 5 ng/mL)	16	6	10
CA199				0.706
阳性(≥37 U/mL)	9	5	4
阴性(< 37 U/mL)	27	12	15
肿瘤最大径				0.044
>4.5 cm	18	12	6
≤4.5 cm	18	5	13
分化程度				0.413
高分化	10	4	6
中分化	19	8	11
低分化	7	5	2
淋巴结转移				0.505
>2个	18	7	11
≤2个	18	10	8
病理分期				0.552
Ⅰ期	2	2	0
Ⅱ期	5	2	3
Ⅲ期	19	8	11
Ⅳ期	10	5	5
术前白蛋白				0.177
阳性(< 40 g/L)	13	4	9
阴性(≥40 g/L)	23	13	10
Ki67				0.684
>80%	7	4	3
≤80%	29	13	16
注：^a组间比较均使用Fisher精确检验。

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表 2 各变量赋值情况

Table 2. Assignment methods of variables

变量	赋值方法
死亡	否=0，是=1
性别	男性=0，女性=1
年龄	≤69岁=0，＞69岁=1
CA199	＜5 ng/mL=0，≥5 ng/mL=1
CEA	＜37 U/mL=0，≥37 U/mL=1
淋巴结转移	＜2个=0，≥2个=1
病理分期	Ⅰ期=0，Ⅱ期=1，Ⅲ期=2，Ⅳ期=3
肿瘤位置	左半结肠=0，右半结肠=1
HTR1D	低表达=0，高表达=1

下载: 导出CSV

表 3 影响结肠癌患者预后的多因素Cox回归分析

Table 3. Cox regression multivariate analysis of prognosis of colon cancer patients

变量	SE	Waldχ²	P值	HR值	95% CI
性别	0.457	2.254	0.133	0.503	0.206~1.233
年龄	0.023	0.002	0.963	0.999	0.955~1.045
CA199	0.001	7.608	0.006	1.002	1.001~1.003
CEA	0.018	0.133	0.716	1.007	0.971~1.043
淋巴结转移	0.062	1.690	0.194	1.084	0.960~1.224
病理分期	0.310	0.575	0.448	1.265	0.689~2.320
肿瘤位置	0.535	3.876	0.049	2.869	1.005~8.195
HTR1D	0.063	5.459	0.019	1.159	1.024~1.312

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