手术标本中生物活性分子表达对结直肠癌腹腔镜术后早期复发转移的预警价值

郭俊宇; 廖驰林; 郭厚基

doi:10.7619/jcmp.20244869

手术标本中生物活性分子表达对结直肠癌腹腔镜术后早期复发转移的预警价值

1.
右江民族医学院附属医院肛肠科, 广西百色, 533000
2.
百色市人民医院心血管内科, 广西百色, 533000

基金项目:

2021年度百色科学研究与技术开发课题百科20213214

2022年度广西高校中青年教师科研基础能力提升项目 2022KY0530

详细信息

通讯作者:
廖驰林

中图分类号: R735.3;R730.1;R446.11
计量
- 文章访问数: 49
- HTML全文浏览量: 9
- PDF下载量: 5
出版历程
- 收稿日期: 2024-10-15
- 修回日期: 2024-12-23
- 刊出日期: 2025-01-27

Warning value of bioactive molecule expression in surgical specimens for early recurrence and metastasis of colorectal cancer after laparoscopic surgery

1.
Anorectal Department, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000
2.
Cardiovascular Department, Baise People's Hospital, Baise, Guangxi, 533000

摘要

摘要:
目的
探讨联合检测手术标本中磷酸甘油酸变位酶1(PGAM1)、微小核糖核酸-433-3p(miR-433-3p)、细胞周期蛋白依赖性激酶1(CDK1)表达对结直肠癌(CRC)腹腔镜术后早期复发转移的预警价值。
方法
回顾性分析120例CRC腹腔镜手术患者的临床资料, 根据术后1年复发转移发生情况分为发生组31例和未发生组89例。比较2组临床资料及手术标本中PGAM1、miR-433-3p、CDK1表达; 采用Logistic回归分析探讨PGAM1、miR-433-3p、CDK1对CRC腹腔镜术后复发转移的影响; 采用受试者工作特征(ROC)曲线分析PGAM1、miR-433-3p、CDK1单独及联合预测腹腔镜术后复发转移的价值，并进行外部验证。
结果
发生组PGAM1 mRNA、CDK1 mRNA水平高于未发生组, miR-433-3p水平低于未发生组，差异有统计学意义(P < 0.05)。Logistic回归分析显示, PGAM1 mRNA(OR=1.387, 95%CI: 1.025~1.877)、miR-433-3p(OR=0.543, 95%CI: 0.319~0.924)、CDK1 mRNA(OR=1.353, 95%CI: 1.108~1.651)均是CRC腹腔镜术后复发转移的独立影响因素(P < 0.05)。ROC曲线分析显示, PGAM1 mRNA、miR-433-3p、CDK1 mRNA联合预测CRC腹腔镜术后复发转移的曲线下面积(AUC)为0.904(95%CI: 0.836~0.950), 优于各指标单独预测效能。个体值预测结果显示，诊断准确率为84.17%的条件下, CRC患者在腹腔镜术后会发生早期复发转移; 外部验证显示，联合预测结果与临床实际结果的Kappa值为0.864(95%CI: 0.611~0.984), 一致性较好。
结论
手术标本中PGAM1、miR-433-3p、CDK1表达均是CRC患者腹腔镜术后早期复发转移的独立影响因素，联合检测对术后复发转移具有较高预测价值。
- 磷酸甘油酸变位酶1 /
- 微小RNA-433-3p /
- 细胞周期蛋白依赖性激酶1 /
- 结直肠癌 /
- 腹腔镜手术 /
- 复发 /
- 转移 /
- 预测价值
Abstract:
Objective
To explore the warning value of expression of phosphoglycerate mutase 1 (PGAM1), microRNA-433-3p (miR-433-3p) and cyclin-dependent kinase 1 (CDK1) in surgical specimens for early recurrence and metastasis after laparoscopic surgery for colorectal cancer (CRC).
Methods
Clinical materials of 120 patients with laparoscopic surgery for CRC were retrospectively analyzed. Based on the incidence status of recurrence and metastasis within one year after surgery, the patients were divided into recurrence group (n=31) and non-recurrence group (n=89). The clinical materials and the expression levels of PGAM1, miR-433-3p, and CDK1 in surgical specimens were compared between the two groups. Logistic regression analysis was conducted to explore the impacts of PGAM1, miR-433-3p and CDK1 on recurrence and metastasis after laparoscopic surgery for CRC. Receiver operating characteristic (ROC) curve was drawn to analyze the values of PGAM1, miR-433-3p and CDK1 alone as well as their combination for predicting recurrence andmetastasis after laparoscopic surgery, and external validation was performed.
Results
The levels of PGAM1 mRNA and CDK1 mRNA in the recurrence group were significantly higher than those in the non-recurrence group, while the level of miR-433-3p was significantly lower (P < 0.05). Logistic regression analysis showed that PGAM1 mRNA (OR=1.387, 95%CI, 1.025 to 1.877), miR-433-3p (OR=0.543, 95%CI, 0.319 to 0.924), and CDK1 mRNA (OR=1.353, 95%CI, 1.108 to 1.651) were all independent factors associated with recurrence and metastasis after laparoscopic surgery for CRC (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) for the combined prediction of recurrence and metastasis after laparoscopic surgery for CRC by PGAM1 mRNA, miR-433-3p, and CDK1 mRNA was 0.904 (95%CI, 0.836 to 0.950), which was superior to the predictive performance of each indicator alone. Individual value prediction results indicated that CRC patients would experience early recurrence and metastasis after laparoscopic surgery under the condition of a diagnostic accuracy rate of 84.17%. External validation showed that the Kappa value between the combined prediction result and the actual clinical result was 0.864 (95%CI, 0.611 to 0.984), indicating good consistency.
Conclusion
The expression levels of PGAM1, miR-433-3p, and CDK1 in surgical specimens are all independent factors influencing early recurrence and metastasis after laparoscopic surgery for CRC patients, and their combined detection has high predictive value for postoperative recurrence and metastasis.
- phosphoglycerate mutase 1 /
- microRNA-433-3p /
- cyclin dependent kinase 1 /
- colorectal cancer /
- laparoscopic surgery /
- recurrence /
- metastasis /
- predictive value

HTML全文

图 1 联合预测因子及各协变量预测术后复发转移的ROC曲线

下载: 全尺寸图片幻灯片

表 1 2组临床资料比较(x±s)[n(%)]

临床资料	分类	发生组(n=31)	未发生组(n=89)	t/χ²/U	P
年龄/岁		65.82±8.00	63.97±10.14	0.920	0.359
性别	男	18(58.06)	55(61.80)	0.134	0.714
	女	13(41.94)	34(38.20)
体质量指数/(kg/m²)		24.15±0.87	24.20±0.79	0.296	0.768
肿瘤位置	直肠	17(54.84)	53(59.55)	0.210	0.647
	结肠	14(45.16)	36(40.45)
肿瘤最大直径/cm		5.94±1.50	5.59±1.74	0.998	0.321
T分期	T₁期	1(3.22)	6(6.74)	0.075	0.784
	T₂+T₃期	30(96.78)	83(93.26)
N分期	N₀期	1(3.22)	5(5.62)	0.002	0.962
	N₁+N₂期	30(96.78)	84(94.38)
分化程度	低分化	6(19.35)	13(14.61)	0.512	0.609
	中分化	14(45.16)	41(46.07)
	高分化	11(35.49)	35(39.32)
肿瘤类型	隆起型	5(16.13)	10(11.23)	0.325	0.745
	溃疡型	25(80.65)	77(86.52)
	浸润型	1(3.22)	2(2.25)
组织学分型	腺癌	23(74.19)	66(74.16)	0.060	0.952
	黏液腺癌	5(16.13)	17(19.10)
	其他	3(9.68)	6(6.74)

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表 2 2组手术标本PGAM1 mRNA、miR-433-3p、CDK1 mRNA比较(x±s)

组别	PGAM1 mRNA	miR-433-3p	CDK1 mRNA
发生组(n=31)	1.04±0.34^**	0.43±0.14^**	1.69±0.55^**
未发生组(n=89)	0.75±0.21	0.68±0.22	0.91±0.30
PGAM1: 磷酸甘油酸变位酶1; CDK1: 细胞周期蛋白依赖性激酶1。与未发生组比较, * * P < 0.01。

下载: 导出CSV

表 3 联合预测模型的构建

变量	β	S. E.	Waldχ²	OR	95%CI		P
变量	β	S. E.	Waldχ²	OR	下限	上限	P
PGAM1 mRNA(X₁)	0.327	0.089	13.515	1.387	1.025	1.877	< 0.001
miR-433-3p(X₂)	-0.611	0.204	8.965	0.543	0.319	0.924	0.004
CDK1 mRNA(X₃)	0.302	0.108	7.818	1.353	1.108	1.651	0.013
常数项	-0.835	0.243	11.801	0.434	—	—	< 0.001

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表 4 联合预测因子及各协变量的预测参数

指标	AUC	95%CI	cut-off值	敏感度/%	特异度/%	P
PGAM1 mRNA(X₁)	0.777	0.692~0.848	0.77	77.42	69.66	< 0.001
miR-433-3p(X₂)	0.754	0.667~0.828	0.46	67.74	71.91	< 0.001
CDK1 mRNA(X₃)	0.758	0.671~0.831	1.32	80.65	64.04	< 0.001
联合预测因子	0.904	0.836~0.950	0.120	80.65	85.39	< 0.001

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表 5 联合预测价值的验证

临床实际	联合预测		总计	一致性	χ²	P	Kappa	95%CI
临床实际	发生	未发生	总计	一致性	χ²	P	Kappa	95%CI
发生	13	2	15
未发生	1	44	45	95.00%	40.248	< 0.001	0.864	0.611~0.984
总计	14	46	60

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参考文献(27)

[1]	SHIN A E, GIANCOTTI F G, RUSTGI A K. Metastatic colorectal cancer: mechanisms and emerging therapeutics[J]. Trends Pharmacol Sci, 2023, 44(4): 222-236. doi: 10.1016/j.tips.2023.01.003
[2]	DIJKSTRA E A, NILSSON P J, HOSPERS G A P, et al. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared with long-course chemoradiotherapy and surgery: a 5-year follow-up of the RAPIDO trial[J]. Ann Surg, 2023, 278(4): e766-e772. doi: 10.1097/SLA.0000000000005799
[3]	MAHMOUD N N. Colorectal cancer: preoperative evaluation and staging[J]. Surg Oncol Clin N Am, 2022, 31(2): 127-141. doi: 10.1016/j.soc.2021.12.001
[4]	LUO J Q, YANG T W, WU J, et al. Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1[J]. Cell Death Dis, 2023, 14(8): 502. doi: 10.1038/s41419-023-06007-4
[5]	ZHANG J, GUO Y H, MA Y R, et al. MiR-433-3p targets AJUBA to inhibit malignant progression of glioma[J]. Neuroimmunomodulation, 2022, 29(1): 44-54. doi: 10.1159/000518084
[6]	HAN Z T, JIA Q, ZHANG J, et al. Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis[J]. J Exp Clin Cancer Res, 2023, 42(1): 228. doi: 10.1186/s13046-023-02781-3
[7]	GUAN T M, LI M, SONG Y, et al. Phosphorylation of USP29 by CDK1 governs TWIST1 stability and oncogenic functions[J]. Adv Sci, 2023, 10(11): e2205873. doi: 10.1002/advs.202205873
[8]	中华医学会肿瘤学分会早诊早治学组. 中国结直肠癌早诊早治专家共识[J]. 中华医学杂志, 2020, 100(22): 1691-1698. doi: 10.3760/cma.j.cn112137-20190924-02103
[9]	IONESCU V A, GHEORGHE G, BACALBASA N, et al. Colorectal cancer: from risk factors to oncogenesis[J]. Medicina, 2023, 59(9): 1646. doi: 10.3390/medicina59091646
[10]	PATEL S G, KARLITZ J J, YEN T, et al. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection[J]. Lancet Gastroenterol Hepatol, 2022, 7(3): 262-274. doi: 10.1016/S2468-1253(21)00426-X
[11]	李忠发, 陈元龙, 李扬. 结直肠癌转录因子激活蛋白2α和2β表达与腹腔镜下根治术后复发的临床关系[J]. 中国内镜杂志, 2023, 29(11): 33-38.
[12]	HOU Y C, ZHANG X T, YAO H, et al. METTL14 modulates glycolysis to inhibit colorectal tumorigenesis in p53-wild-type cells[J]. EMBO Rep, 2023, 24(4): e56325. doi: 10.15252/embr.202256325
[13]	SUN X D, HE L F, LIU H, et al. The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity[J]. Cell Metab, 2023, 35(9): 1563-1579, e8. doi: 10.1016/j.cmet.2023.07.005
[14]	于文文, 李舒展, 王敏, 等. 磷酸甘油酸变位酶1在结直肠癌组织中的表达及其对患者预后和癌细胞恶性生物学行为的影响[J]. 中国肿瘤生物治疗杂志, 2023, 30(10): 862-867.
[15]	LIU M, LI R M, WANG M, et al. PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway[J]. Mol Oncol, 2022, 16(15): 2843-2860. doi: 10.1002/1878-0261.13259
[16]	MATTHEWS H K, BERTOLI C, DE BRUIN R A M. Cell cycle control in cancer[J]. Nat Rev Mol Cell Biol, 2022, 23(1): 74-88. doi: 10.1038/s41580-021-00404-3
[17]	金熠蓉, 储屹, 吴开春, 等. Sec62对结直肠癌细胞的增殖作用及其潜在机制[J]. 空军军医大学学报, 2022, 43 (4): 309-314.
[18]	王国强, 张纲, 唐建坡, 等. SOX4通过靶向调节miR-17表达水平对结直肠癌细胞免疫逃逸及细胞迁移的影响[J]. 检验医学与临床, 2024, 21(13): 1825-1830.
[19]	WANG Q S, BODE A M, ZHANG T S. Targeting CDK1 in cancer: mechanisms and implications[J]. NPJ Precis Oncol, 2023, 7(1): 58. doi: 10.1038/s41698-023-00407-7
[20]	ZENG K X, LI W H, WANG Y, et al. Inhibition of CDK1 overcomes oxaliplatin resistance by regulating ACSL4-mediated ferroptosis in colorectal cancer[J]. Adv Sci, 2023, 10(25): e2301088. doi: 10.1002/advs.202301088
[21]	LIU F, ZHU C M, MA H, et al. Curcumin targets miR-134-5p to suppress the progression of colorectal cancer through regulating the CDCA3/CDK1 pathway[J]. Naunyn Schmiedebergs Arch Pharmacol, 2024, 397(1): 109-122. doi: 10.1007/s00210-023-02584-5
[22]	DING L, XU Y J, XU L, et al. Programmed cell death 11 modulates but not entirely relies on p53-HDM2 loop to facilitate G2/M transition in colorectal cancer cells[J]. Oncogenesis, 2023, 12(1): 57. doi: 10.1038/s41389-023-00501-2
[23]	LU P F, YU Z N, WANG K N, et al. DDX21 interacts with WDR5 to promote colorectal cancer cell proliferation by activating CDK1 expression[J]. J Cancer, 2022, 13(5): 1530-1539. doi: 10.7150/jca.69216
[24]	LOBERA E S, VARELA M A, JIMENEZ R L, et al. miRNA as biomarker in lung cancer[J]. Mol Biol Rep, 2023, 50(11): 9521-9527. doi: 10.1007/s11033-023-08695-9
[25]	QU J X, CHEN Q Y, BING Z Q, et al. C. tropicalis promotes CRC by down-regulating tumor cell-intrinsic PD-1 receptor via autophagy[J]. J Cancer, 2023, 14(10): 1794-1808. doi: 10.7150/jca.79664
[26]	MAO Z H, LIN D P, XU J. Hsa_circ_0001535 regulates colorectal cancer progression via the miR-433-3p/RBPJ axis[J]. Biochem Genet, 2023, 61(3): 861-878. doi: 10.1007/s10528-022-10287-4
[27]	白雨微, 黄小齐, 刘航, 等. 微小RNA-433-3p靶向调控RAP1A对结直肠癌细胞生物学行为的影响[J]. 临床肿瘤学杂志, 2022, 27(12): 1092-1098.

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