盐诱导激酶<strong>2</strong>与结直肠癌伴慢性血吸虫病淋巴结转移的相关性研究

doi:10.3724/zdxbyxb-2021-0157

浙江大学学报（医学版）

2021, Vol. 50

Issue (5): 607-613 DOI: 10.3724/zdxbyxb-2021-0157

原著

盐诱导激酶2与结直肠癌伴慢性血吸虫病淋巴结转移的相关性研究

吴超¹,王羽²,高红亮¹,张逸³,戴敏^3,*(

),李曙^1,*(

)

1.皖南医学院基础医学院，安徽芜湖 241002
2.皖南医学院第二附属医院肾内科，安徽芜湖 241002
3.芜湖市第二人民医院病理科，安徽芜湖 241002

Relationship between salt-inducible kinase 2 (SIK2) and lymph node metastasis in colorectal cancer patients complicated with chronic schistosomiasis

WU Chao¹,WANG Yu²,GAO Hongliang¹,ZHANG Yi³,DAI Min^3,*(

),LI Shu^1,*(

)

1. Department of Basic Medical School, Wannan Medical College, Wuhu 241002, Anhui Province, China;
2. Hemodialysis Center, the Second Affiliated Hospital of Wannan Medical College, Wuhu 241002, Anhui Province, China;
3. Department of Pathology, Wuhu Second People’s Hospital, Wuhu 241002, Anhui Province, China

全文: PDF(17121 KB)

HTML( 13 )

摘要：

目的：探究慢性血吸虫病影响结直肠癌的发生发展是否与盐诱导激酶2（SIK2）相关。方法：标本来自于2015年6月至2020年6月在芜湖市第二人民医院就诊并经临床和病理检查诊断为结直肠癌的363例手术患者，其中结直肠癌伴慢性血吸虫病（CRC-S）患者56例，结直肠癌不伴慢性血吸虫病（CRC-NS）患者307例。对患者临床资料和病理诊断结果进行统计，分析慢性血吸虫病与结直肠癌的相关性。利用免疫组化和蛋白质印迹法检测SIK2在各组结直肠癌标本中的分布和表达情况，分析SIK2与CRC-S患者肿瘤淋巴结转移的相关性。结果：CRC-S组淋巴结转移率（62.5%）高于CRC-NS组（47.2%）（P<0.05）。CRC-S伴淋巴结转移患者血吸虫卵主要分布在肿瘤组织（25/35，71.4%），CRC-S不伴淋巴结转移患者血吸虫卵主要分布在癌旁组织（17/21，81.0%），差异有统计学意义（χ²=14.243，P<0.01）。SIK2主要位于胞质溶胶，其在肿瘤组织中的表达高于癌旁组织。与CRC-NS组比较，CRC-S组SIK2表达显著增加，且伴淋巴结转移的患者SIK2表达水平高于不伴淋巴结转移的患者，虫卵位于肿瘤组织的患者SIK2表达水平高于虫卵位于癌旁组织的患者（均P<0.01）。结论：CRC-S患者淋巴结转移率更高，且虫卵位于肿瘤组织时，更容易发生淋巴结转移。SIK2的表达水平与是否伴发慢性血吸虫病、虫卵分布部位以及淋巴转移具有相关性。

关键词： 结直肠癌; 血吸虫病; 淋巴结转移; 盐诱导激酶2; 血吸虫卵

Abstract:

Objective:To investigate the relationship between salt-inducible kinase 2 (SIK2) and lymph node metastasis in colorectal cancer patients complicated with chronic schistosomiasis. Methods:Tissue specimens were collected from 363 patients who were diagnosed as colorectal cancer by clinical and pathological examination in Wuhu Second People’s Hospital from June 2015 to June 2020. Fifty-six patients were colorectal cancer complicated with schistosomiasis (CRC-S) and 307 patients were colorectal cancer not complicated with schistosomiasis (CRC-NS). The clinical and pathological data of the patients were analyzed to explore the relationship between chronic schistosomiasis and colorectal cancer. Immunohistochemistry and Western blotting were used to detect the distribution and expression of SIK2 in colorectal cancer specimens. The relationship between SIK2 and lymph node metastasis of CRC-S was analyzed. Results:The rate of lymph node metastasis in CRC-S group was significantly higher than that in CRC-NS group (62.5% vs. 47.2%, P<0.05). In CRC-S patients with lymph node metastasis, schistosome eggs were distributed mainly in tumor tissues (25/35, 71.4%), while in patients with CRC-S without lymph node metastasis, schistosome eggs were distributed mainly in paracancerous tissues (17/21, 81.0%) (χ²=14.243, P<0.01). The SIK2 was mainly located in cytosol, and its expression in tumor tissues was higher than that in paracancerous tissues. Compared with CRC-NS patients, the expression of SIK2 in CRC-S patients was significantly increased; the expression of SIK2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis; and the expression of SIK2 in patients with schistosome eggs in cancer tissues was higher than that in patients with schistosome eggs in paracancerous tissues (allP<0.01).Conclusions:Lymph node metastasis is more likely to be occurred in colorectal cancer patients with schistosomiasis, especially in those with schistosome eggs in tumor tissues. The expression of SIK2 may be correlated with chronic schistosomiasis, egg distribution and lymphatic metastasis.

Key words: Colorectal cancer Schistosomiasis Lymph node metastasis Salt-inducible kinase 2 Schistosome egg

收稿日期: 2021-06-02 出版日期: 2021-12-29

R735.3

基金资助: 安徽省高校科学研究项目（KJ2020ZD55，KJ2020A0604）；安徽省重点研究与开发计划（S202104j07020117）；皖南医学院校级重点项目（22040219001）

通讯作者: 戴敏,李曙 E-mail: 453812523@qq.com

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	吴超
	王羽
	高红亮
	张逸
	戴敏
	李曙

引用本文:

吴超,王羽,高红亮,张逸,戴敏,李曙. 盐诱导激酶2与结直肠癌伴慢性血吸虫病淋巴结转移的相关性研究[J]. 浙江大学学报（医学版）, 2021, 50(5): 607-613.

WU Chao,WANG Yu,GAO Hongliang,ZHANG Yi,DAI Min,LI Shu. Relationship between salt-inducible kinase 2 (SIK2) and lymph node metastasis in colorectal cancer patients complicated with chronic schistosomiasis. J Zhejiang Univ (Med Sci), 2021, 50(5): 607-613.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0157 或 https://www.zjujournals.com/med/CN/Y2021/V50/I5/607

表 1 CRC-S组与CRC-NS组病理学诊断结果比较

图 1 结直肠癌伴慢性血吸虫病患者肠组织血吸虫卵分布（苏木精–伊红染色）红色箭头指示血吸虫卵，蓝色箭头指示肿瘤组织，黑色圈标记为放大区域.

图 2 盐诱导激酶2在结直肠癌患者组织中的表达情况A：CRC-NS伴淋巴结转移；B：CRC-NS不伴淋巴结转移；C：CRC-S伴淋巴结转移（虫卵位于肿瘤组织）；D：CRC-S不伴淋巴结转移（虫卵位于肿瘤组织）；E：CRC-S伴淋巴结转移（虫卵位于癌旁组织）；F：CRC-S不伴淋巴结转移（虫卵位于癌旁组织）. 红色箭头指示正常腺体，蓝色箭头指示肿瘤组织，黑色圈标记为放大区域（各组图中上图标尺=500 μm，下图标尺=100 μm）. CRC-NS：结直肠癌不伴慢性血吸虫病；CRC-S：结直肠癌伴慢性血吸虫病.

图 3 结直肠癌患者组织中SIK2蛋白表达电泳图A：CRC-NS伴淋巴结转移；B：CRC-NS不伴淋巴结转移；C：CRC-S伴淋巴结转移（虫卵位于肿瘤组织）；D：CRC-S不伴淋巴结转移（虫卵位于肿瘤组织）；E：CRC-S伴淋巴结转移（虫卵位于癌旁组织）；F：CRC-S不伴淋巴结转移（虫卵位于癌旁组织）. CRC-NS：结直肠癌不伴慢性血吸虫病；CRC-S：结直肠癌伴慢性血吸虫病；SIK2：盐诱导激酶2；GAPDH：甘油醛-3-磷酸脱氢酶.

1	STOFFELE M, MURPHYC C. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults[J]Gastroenterology, 2020, 158( 2): 341-353. doi: 10.1053/j.gastro.2019.07.055
2	NFONSAMV N, JECIUSH, CHEND, et al.Increasing incidence of colon cancer in the young: assessing the tumor biology[J]J Am Coll Surg, 2019, 229( 1): 79-90. doi: 10.1016/j.jamcollsurg.2019.03.022
3	AUYEUNGK K, KOJ K. Angiogenesis and oxidative stress in metastatic tumor progression: pathogenesis and novel therapeutic approach of colon cancer[J]Curr Pharm Des, 2017, 23( 27): 3952-3961. doi: 10.2174/1381612823666170228124105
4	BENSONA B, VENOOKA P, AL-HAWARYM M, et al.NCCN guidelines insights: colon cancer, version 2.2018[J]J Natl Compr Canc Ne, 2018, 16( 4): 359-369. doi: 10.6004/jnccn.2018.0021
5	SOLIMANN A, KESHKW A, SHOHEIBZ S, et al.Inflammation, oxidative stress and L-fucose as indispensable participants in schistosomiasis-associated colonic dysplasia[J]Asian Pac J Cancer Prev, 2014, 15( 3): 1125-1131. doi: 10.7314/APJCP.2014.15.3.1125
6	WUC, DUX, TANGL, et al.Protein promotes tumor development via the receptor for advanced glycation end products (RAGE)[J]Front Immunol, 2020, 1767. doi: 10.3389/fimmu.2020.01767
7	HAMIDH K S. Schistosoma japonicum-associated colorectal cancer: a review[J]Am J Tropical Med Hyg, 2019, 100( 3): 501-505. doi: 10.4269/ajtmh.18-0807
8	CHENF, CHENL, QINQ, et al.Salt-inducible kinase 2: an oncogenic signal transmitter and potential target for cancer therapy[J]Front Oncol, 2019, 18. doi: 10.3389/fonc.2019.00018
9	张祎婕. HIPPO信号通路在血吸虫病肝纤维化中的调控机制研究[D]. 武汉: 华中科技大学, 2019 ZHANG Yijie. The role of HIPPO pathway in liver fibrosis caused by Schistosoma japonicum infection [D]. Wuhan: Huazhong University of Science and Technology, 2019. (in Chinese)
10	王子健, 杨江华. 日本血吸虫病对胃癌和结直肠癌发生的影响[J]. 中国血吸虫病防治杂志, 2020, 32(2): 148-153 WANG Zijian, YANG Jianghua. Effect of schistosomiasis japonica on the development of gastric and colorectal cancer[J]. Chinese Journal of Schistosomiasis Control, 2020, 32(2): 148-153. (in Chinese)
11	杨兴广, 杨继武, 赵鹏举, 等. Bcl-2与Bax基因在结直肠癌合并血吸虫病患者体内表达及临床病理意义[J]. 中国血吸虫病防治杂志, 2021, 33(2): 148-153 YANG Xingguang, YANG Jiwu, ZHAO Pengju, et al. Expression and clinicopathological significance of Bcl-2 and Bax genes in colorectal cancer patients complicated with schistosomiasis[J]. Chinese Journal of Schistosomiasis Control, 2021, 33(2): 148-153. (in Chinese)
12	WANGM, ZHANGY C, YANGX Y, et al.Prognostic analysis of schistosomal rectal cancer[J]Asian Pac J Cancer Prev, 2014, 15( 21): 9271-9275. doi: 10.7314/APJCP.2014.15.21.9271
13	LI S, MARTIN A. Mismatch repair and colon cancer: mechanisms and therapies explored[J]. Trends Mol Med, 2016, 22(4): 274-289
14	陈寅波, 刘卓, 钱俊, 等. DNA错配修复基因hMLH1与hMSH2在结直肠癌合并慢性血吸虫肠病与散发型结直肠癌中表达的差异研究[J]. 中华胃肠外科杂志, 2016, 19(1): 75-79 CHEN Yinbo, LIU Zhuo, QIAN Jun, et al. Expression difference of DNA mismatch repair gene hMLH1 and hMSH2 between schistosomiasis-associated colorectal cancer and sporadic colorectal cancer[J]. Chinese Journal of Gastrointestinal Surgery, 2016, 19(1): 75-79. (in Chinese)
15	LIUY, GAOS, CHENX, et al.Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2)[J]Tumour Biol, 2016, 37( 9): 12231-12239. doi: 10.1007/s13277-016-5066-2
16	ZHAOJ, ZHANGX, GAOT, et al.SIK2 enhances synthesis of fatty acid and cholesterol in ovarian cancer cells and tumor growth through PI3K/Akt signaling pathway[J]Cell Death Dis, 2020, 11( 1): 25. doi: 10.1038/s41419-019-2221-x
17	ZHANGM X, WANGH, SUNG P. Tumor‐suppressor Fbxw7 targets SIK2 for degradation to interfere with TORC2‐AKT signaling in pancreatic cancer[J]Cell Biol Int, 2020, 44( 9): 1900-1910. doi: 10.1002/cbin.11396
18	SIK2 promotes ovarian cancer spread[J]. Cancer Discov. 2016, 6(10): OF1
19	韩连秀, 杨江华. 血吸虫病与结直肠肿瘤关系的研究现状[J]. 中国病原生物学杂志, 2018, 13(2): 210-212 HAN Lianxiu, YANG Jianghua. Study on the relationship between schistosomiasis and colorectal tumors[J]. Chinese Journal of Pathogen Biology, 2018, 13(2): 210-212. (in Chinese)
20	WANG W, JING H, LIU J, rt al. Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer[J]. World J Surg Oncol, 2021, 19(1): 321
21	DASGUPTAB, CHHIPAR R. Evolving lessons on the complex role of AMPK in normal physiology and cancer[J]Trends Pharmacol Sci, 2016, 37( 3): 192-206. doi: 10.1016/j.tips.2015.11.007

[1]	张冉,刘云,张翠,马梦尧,李曙,洪云. 盐诱导激酶2对脑缺血再灌注大鼠脑组织能量代谢的影响[J]. 浙江大学学报（医学版）, 2021, 50(3): 352-360.
[2]	周卉卉;吕炳建;来茂德. 遗传性MUTYH基因突变与结直肠癌[J]. 浙江大学学报（医学版）, 2007, 36(4): 406-411.
[3]	来茂德，黄琼，Parwaresch Reza. 一种可能的结直肠癌早期病变[J]. 浙江大学学报（医学版）, 2004, 33(2): 115-117.
[4]	鲁裕玉，沈朋，陈丽荣. 喉癌微血管密度与细胞DNA含量参数的定量研究[J]. 浙江大学学报（医学版）, 2001, 30(2): 73-75.
[5]	林善钦, 林建灿. 245例晚期血吸虫病巨脾切除的体会[J]. 浙江大学学报（医学版）, 1993, 22(6): 276-277.
[6]	林瑞炮, 马亦林. 慢性血吸虫病患者周围血淋巴细胞亚群测定[J]. 浙江大学学报（医学版）, 1992, 21(5): 217-219.
[7]	吴志良, 张悟澄, 陈碧珍, 叶爱民. 五种抗原用酶联免疫吸附试验诊断血吸虫病的研究[J]. 浙江大学学报（医学版）, 1991, 20(4): 164-165.
[8]	陈碧珍, 林筱勇, 黄天威, 张才康, 周晓音. 肝卵组织石蜡切片间接荧光抗体试验诊断日本血吸虫病的进一步研究[J]. 浙江大学学报（医学版）, 1990, 19(2): 61-63.
[9]	吴德仁, 邵毓文, 马新源, 卜静华. 嘉善县1977~1987年大肠癌流行病学研究[J]. 浙江大学学报（医学版）, 1989, 18(5): 214-217.
[10]	林筱勇, 陈碧珍, 黄天威, 张才康, 周晓音. 荧光素标记金葡菌A蛋白作间接荧光抗体试验检测日本血吸虫抗体[J]. 浙江大学学报（医学版）, 1989, 18(3): 110-111.
[11]	张才康, 陈碧珍, 黄天威, 周晓音, 林筱勇. 肝卵石蜡切片酶联葡萄球菌A蛋白免疫酶染色检测血吸虫病抗体[J]. 浙江大学学报（医学版）, 1988, 17(6): 245-247.
[12]	陈金泉, 郁金声, 胡颖坚, 蔡卫民, 傅宝珍. 晚期血吸虫病39例放射性核素肝脏扫描图象初步分析[J]. 浙江大学学报（医学版）, 1987, 16(4): 169-169.

Viewed

Full text

Abstract

Cited

Shared

Discussed