转钴胺素1在结肠癌及肺转移瘤中的表达水平及与患者临床特征和预后的关系

doi:10.3877/cma.j.issn.1674-0785.2021.11.018

中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (11) : 904 -910. doi: 10.3877/cma.j.issn.1674-0785.2021.11.018

基础研究

转钴胺素1在结肠癌及肺转移瘤中的表达水平及与患者临床特征和预后的关系

刘广杰¹, 于淼², 张娟³, 马洪庆³, 胡旭华³, 邓明坤⁴, 潘红梅⁴, 王贵英⁵^,^†(

)

^1. 050011　石家庄，河北医科大学第四医院胸外科
^2. 050017　石家庄，河北医科大学基础医学院
^3. 050011　石家庄，河北医科大学第四医院第二外科
^4. 054800　河北邢台，河北省邢台市清河中心医院外科
^5. 050011　石家庄，河北医科大学第四医院第二外科；050001　石家庄，河北医科大学第三医院胃肠外科

收稿日期:2021-08-23 出版日期:2021-11-15
通信作者: 王贵英
基金资助:
国家癌症中心肿瘤科研专项课题(NCC2017A23)

TCN1 expression in colon cancer and metastatic tumor tissues and its relationship with clinical features and prognosis

Guangjie Liu¹, Miao Yu², Juan Zhang³, Hongqing Ma³, Xuhua Hu³, Mingkun Deng⁴, Hongmei Pan⁴, Guiying Wang⁵^,^†()

^1. Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
^2. School of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China
^3. Second Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
^4. Department of Surgery, Qinghe Central Hospital, Xingtai 054800, China
^5. Second Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China; Department of Gastrointestinal Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang 050001, China

Received:2021-08-23 Published:2021-11-15
Corresponding author: Guiying Wang

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引用本文：

刘广杰, 于淼, 张娟, 马洪庆, 胡旭华, 邓明坤, 潘红梅, 王贵英. 转钴胺素1在结肠癌及肺转移瘤中的表达水平及与患者临床特征和预后的关系[J]. 中华临床医师杂志(电子版), 2021, 15(11): 904-910.

Guangjie Liu, Miao Yu, Juan Zhang, Hongqing Ma, Xuhua Hu, Mingkun Deng, Hongmei Pan, Guiying Wang. TCN1 expression in colon cancer and metastatic tumor tissues and its relationship with clinical features and prognosis[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(11): 904-910.

目的

探讨转钴胺素1（TCN1）在结肠癌组织、癌旁对照组织及肺移瘤组织中的表达水平及与患者临床特征和预后的关系。

方法

选取2013年1月至2014年6月在河北医科大学第四医院第二外科经手术切除的212例结肠癌患者蜡块标本制作病理芯片，采用免疫组化SP法测定结肠癌组织、癌旁对照组织及转移瘤组织中的TCN1表达水平并利用结肠腺癌（COAD）生信数据库进行TCN1 mRNA表达水平验证，结合随访资料探讨TCN1表达水平与患者临床特征和预后的关系。

结果

TCN1在结肠癌组织中的阳性表达率为71.70%（152/212），明显高于癌旁对照组织3.77%（8/212），两者比较差异有统计学意义（P＜0.001）。生信数据挖掘发现结肠癌中TCN1mRNA水平呈高表达（结肠癌：5.829±3.336 vs 正常黏膜组织：1.298±1.085）。TCN1在肺转移组织中阳性表达率为100%。新辅助化疗后患者TCN1表达水平下降（5.29±3.06 vs 3.88±1.78，P=0.009）。TCN1表达水平与分期及肿瘤位置相关，分期增加阳性表达率升高（P＜0.05），与患者性别（P=0.601）、年龄（P=0.376）、消化道病史（P=0.240）、吸烟史（P=0.068）、饮酒史（P=0.512）及病理类型（P=0.319）无关。单因素Cox回归分析显示，M分期（P=0.035）、TNM分期（P=0.014）及TCN1表达水平（P=0.042）是结肠癌预后相关因素。全组患者5年生存率为64.62%，TCN1阴性组为76.67%，阳性组为59.87%，差异有统计学意义（P=0.031）。多因素Cox回归分析显示，M分期（P=0.044）和TCN1（P=0.047）表达水平是结肠癌预后独立影响因素。

结论

TCN1在结肠癌及其转移组织中高表达且与预后相关，可以作为预后评价的生物学标志物。

关键词: 结肠癌, 转钴胺素1, 预后, 临床特征

Objective

To reveal the TCN1 expression status in colon cancer tissues, adjacent control tissues, and metastatic tumor tissues and discuss the relationship of TCN1 expression level with the clinical characteristics and prognosis of colon cancer patients.

Methods

A total of 212 patients with colon cancer who underwent tumor resection were enrolled from January 2013 to June 2014 at the Second Department of Surgery of Fourth Hospital of Hebei Medical University. Surgically resected specimens were selected to make pathological chips and for immunohistochemistry. The TCN1 expression colon adenocarcinoma (COAD) bioinformatics database was selected and bioinformatics technology was used to verify the TCN1 mRNA expression level in colon cancer tissues. Follow-up data was employed to discuss the relationship between the expression level of TCN1 and clinical characteristics and prognosis of colon cancer.

Results

The positive expression rate of TCN1 in colon cancer tissues was 71.70% (152/212), which was significantly higher than that in adjacent tissues (3.77% [8/212]; P＜0.001). Bioinformatics analysis of the COAD database verified that TCN1 was highly expressed in colon cancer tissues at the mRNA level (colon cancer tissues: 5.829±3.336 vs normal colon mucosal tissues:1.298±1.085). The positive expression rate of TCN1 in lung metastasis tissue was 100%, which was consistent with the expression level in primary colon cancer. After neoadjuvant chemotherapy, the expression of TCN1 decreased (5.29±3.06 vs 3.88±1.78, P=0.009). The expression level of TCN1 was positively correlated with clinical stage and caner location, and the positive expression rate increased with advanced stage (P＜0.05). In contrast, TCN1 expression level was not related with sex (P=0.601), age (P=0.376), history of diseases of the digestive system (P=0.240), smoking history (P=0.068), drinking history (P=0.512), or pathologic type (P=0.319). Univariate Cox regression analysis showed that M stage (P=0.035), TNM stage (P=0.014), and TCN1 expression level (P=0.042) were prognostic factors for colon cancer. The 5-year survival rate was 64.62% in the whole cohort, 76.67% in the TCN1 negative expression group, and 59.87% in the positive expression group (P=0.031); there was a significant difference between the two group (P=0.031). Cox multiple regression analysis showed that M stage (P=0.044) and TCN1 expression status (P=0.047) were independent prognostic factors.

Conclusion

TCN1 is highly expressed in colon cancer and colon cancer metastatic tissues, and the expression level is related to prognosis and can be used as a prognostic biomarker.

Key words: Colon cancer, Transcobalamin 1, Prognosis, Clinical features

图1 不同组织中转钴胺素1（TCN1）表达情况（免疫组化，×200）。图a为正常结肠黏膜；图b~d为结肠癌组织中TCN1表达情况，其中图b为阴性，图c为低表达，图d为高表达；图e为正常肺组织；图f为结肠癌肺转移瘤组织

表1 转钴胺素1（TCN1）表达水平与结肠癌患者临床特征的关系（例）

项目	例数	TCN1表达状态		χ²值	P值
项目	例数	阳性	阴性	χ²值	P值
性别				0.274	0.601
男	105	77	28
女	107	75	32
年龄				0.783	0.376
＜60岁	95	71	24
≥60岁	117	81	36
肿瘤位置				5.538	0.019
右半结肠	107	69	38
左半结肠	105	83	22
消化道病史				1.379	0.240
无	109	82	27
有	103	70	33
吸烟史				3.347	0.068
无	99	65	34
有	113	87	26
饮酒史				0.437	0.512
无	103	76	27
有	109	76	33
消化道梗阻				0.376	0.540
无	136	87	49
有	66	55	11
T分期				13.026	0.005
T1	3	1	2
T2	15	6	9
T3	50	33	17
T4	144	112	32
N分期				10.501	0.005
N0	127	82	45
N1	71	56	15
N2	14	14	0
M分期				9.201	0.002
M0	191	131	60
M1	21	21	0
TNM分期				22.446	＜0.001
Ⅰ期	18	6	12
Ⅱ期	107	74	33
Ⅲ期	67	52	15
Ⅳ期	20	20	0
病理类型				0.663	0.319
腺癌	168	123	45
黏液腺癌	14	7	7
其他类型	30	22	8
肺组织				1.086	0.025
肺转移组织	37	37	0
正常肺组织	37	6	31

表1 转钴胺素1（TCN1）表达水平与结肠癌患者临床特征的关系（例）

项目	例数	TCN1表达状态		χ²值	P值
项目	例数	阳性	阴性	χ²值	P值
性别				0.274	0.601
男	105	77	28
女	107	75	32
年龄				0.783	0.376
＜60岁	95	71	24
≥60岁	117	81	36
肿瘤位置				5.538	0.019
右半结肠	107	69	38
左半结肠	105	83	22
消化道病史				1.379	0.240
无	109	82	27
有	103	70	33
吸烟史				3.347	0.068
无	99	65	34
有	113	87	26
饮酒史				0.437	0.512
无	103	76	27
有	109	76	33
消化道梗阻				0.376	0.540
无	136	87	49
有	66	55	11
T分期				13.026	0.005
T1	3	1	2
T2	15	6	9
T3	50	33	17
T4	144	112	32
N分期				10.501	0.005
N0	127	82	45
N1	71	56	15
N2	14	14	0
M分期				9.201	0.002
M0	191	131	60
M1	21	21	0
TNM分期				22.446	＜0.001
Ⅰ期	18	6	12
Ⅱ期	107	74	33
Ⅲ期	67	52	15
Ⅳ期	20	20	0
病理类型				0.663	0.319
腺癌	168	123	45
黏液腺癌	14	7	7
其他类型	30	22	8
肺组织				1.086	0.025
肺转移组织	37	37	0
正常肺组织	37	6	31

图2 COAD数据库中验证转钴胺素1（TCN1）mRNA在结肠癌患者不同组织中的表达水平

图3 转钴胺素1（TCN1）不同表达状态的结肠癌患者生存曲线

表2 结肠癌患者预后影响因素的单因素Cox回归分析

项目	例数	5年生存率（%）	HR值	95%CI	P值
性别			0.968	0.648~1.448	0.876
男	105	63.81
女	107	65.42
年龄			0.997	0.981~1.014	0.754
＜60岁	107	60.78
≥60岁	105	68.18
肿瘤部位			0.803	0.537~1.201	0.285
右半结肠	107	57.14
左半结肠	105	71.96
消化道病史			0.746	0.472~1.179	0.209
无	109	60.55
有	103	68.93
吸烟史			0.754	0.479~1.187	0.223
无	109	60.61
有	103	68.14
饮酒史			0.785	0.499~1.235	0.295
无	103	61.17
有	109	67.89
消化道梗阻			0.558	0.268~1.162	0.119
无	136	61.93
有	66	77.78
病理类型			0.789	0.519~1.073	0.131
腺癌	168	64.29
黏液腺癌	14	66.67
其他	30	65.52
T分期			1.128	0.833~1.529	0.437
T1	3	100.00
T2	15	66.67
T3	50	68.00
T4	144	62.50
N分期			1.117	0.815~1.532	0.491
N0	127	68.50
N1	71	56.34
N2	14	71.43
M分期			1.878	1.044~3.380	0.035
M0	191	42.86
M1	21	67.02
TNM分期			1.236	0.951~1.608	0.014
Ⅰ	18	72.22
Ⅱ	107	67.29
Ⅲ	67	65.67
Ⅳ	20	40.00
TCN1表达			1.560	0.961~2.534	0.042
阳性	152	76.67
阴性	60	59.87

表2 结肠癌患者预后影响因素的单因素Cox回归分析

项目	例数	5年生存率（%）	HR值	95%CI	P值
性别			0.968	0.648~1.448	0.876
男	105	63.81
女	107	65.42
年龄			0.997	0.981~1.014	0.754
＜60岁	107	60.78
≥60岁	105	68.18
肿瘤部位			0.803	0.537~1.201	0.285
右半结肠	107	57.14
左半结肠	105	71.96
消化道病史			0.746	0.472~1.179	0.209
无	109	60.55
有	103	68.93
吸烟史			0.754	0.479~1.187	0.223
无	109	60.61
有	103	68.14
饮酒史			0.785	0.499~1.235	0.295
无	103	61.17
有	109	67.89
消化道梗阻			0.558	0.268~1.162	0.119
无	136	61.93
有	66	77.78
病理类型			0.789	0.519~1.073	0.131
腺癌	168	64.29
黏液腺癌	14	66.67
其他	30	65.52
T分期			1.128	0.833~1.529	0.437
T1	3	100.00
T2	15	66.67
T3	50	68.00
T4	144	62.50
N分期			1.117	0.815~1.532	0.491
N0	127	68.50
N1	71	56.34
N2	14	71.43
M分期			1.878	1.044~3.380	0.035
M0	191	42.86
M1	21	67.02
TNM分期			1.236	0.951~1.608	0.014
Ⅰ	18	72.22
Ⅱ	107	67.29
Ⅲ	67	65.67
Ⅳ	20	40.00
TCN1表达			1.560	0.961~2.534	0.042
阳性	152	76.67
阴性	60	59.87

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TCN1 expression in colon cancer and metastatic tumor tissues and its relationship with clinical features and prognosis

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TCN1 expression in colon cancer and metastatic tumor tissues and its relationship with clinical features and prognosis