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结直肠癌(CRC)是全球第三大最常见的癌症,也是癌症相关死亡的第二大常见原因。结直肠癌肝转移(CRLM)是导致CRC患者死亡的主要原因,根治性肝切除术是目前有望治愈CRLM的唯一途径,但大部分患者不能进行根治性肝切除术。通过早期发现并进行针对性干预,能够改善患者的治疗效果及预后。文章通过综述CRLM的发病机制、诊疗现状及最新纳米诊疗方法,为深入探索高效诊疗方法提供思路。
Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related death worldwide.Colorectal cancer liver metastases(CRLM)are the leading cause of death in patients with CRC.Radical hepatectomy is the only way to cure CRLM so far,while most patients cannot undergo radical hepatectomy.CRLM treatment efficacy and prognosis can be improved by early diagnosis and specialized intervention.This paper reviews the pathogenesis,diagnosis,and treatment status of CRLM and the latest nano-diagnosis and treatment methods so as to provide ideas for in-depth exploration of efficient diagnosis and treatment methods.
目的 探讨转录因子E盒结合锌指蛋白1(ZEB1)、溶酶体相关膜蛋白5(LAMP5)在结直肠癌组织中的表达水平分析及预后预测价值。方法 选取驻马店市中心医院2018年1月—2020年1月收治的120例结直肠癌患者,分别采取所有患者的结直肠癌组织及癌旁组织进行免疫组化染色,对比ZEB1、LAMP5阳性率。对比不同病理特征结直肠癌患者ZEB1、LAMP5表达水平差异。对所有患者进行4年随访,依照随访结果将患者分为2个亚组,即预后不良组(n=35)和预后良好组(n=85),对比两组患者一般临床特征及ZEB1、LAMP5表达水平,应用Logistic回归分析ZEB1、LAMP5对结直肠癌预后的预测价值。结果 结直肠癌组织ZEB1、LAMP5相对表达量(38.26±5.49、26.77±3.85)与ZEB1、LAMP5阳性率(86.67%、72.22%)高于癌旁组织(15.46±2.54、8.04±1.59、23.33%、15.56%],对比差异有统计学意义(t=41.280,χ2=25.437;t=49.255,χ 2 =16.071;P<0.05)。不同TNM分期[Ⅰ~Ⅱ期(35.55±4.13)、Ⅲ~Ⅳ期(42.32±4.75)]、淋巴结转移患者[是(44.37±4.28)、否(35.84±3.77)]、肿瘤分化程度[低分化(35.27±4.57)、中高分化(41.34±4.60)]ZEB1相对表达量对比差异有统计学意义(t=-8.281,P<0.001;t=10.746,P<0.001;t=-7.253,P<0.001);不同TNM分期[Ⅱ期(24.88±3.37)、Ⅲ~Ⅳ期(29.61±2.57)]、淋巴结转移[是(30.72±2.19)、否(25.21±3.19)]、肿瘤分化程度[低分化(24.57±3.62)、中高分化(29.04±2.55)]患者LAMP5相对表达量对比差异有统计学意义(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001);预后良好组与预后不良组患者性别、年龄、大体类型、肿瘤大小对比差异无统计学意义(P>0.05),预后良好组与预后不良组患者TNM分期、淋巴结转移、肿瘤分化程度、ZEB1、LAMP5阳性比例对比差异有统计学意义(P<0.05);Logistic回归分析显示:淋巴结转移、ZEB1阳性、LAMP5阳性为结直肠癌预后不良独立预测因素(P<0.05)。结论 ZEB1、LAMP5在结直肠癌组织中呈现高表达状态,且与结直肠癌的发生有关,同时ZEB1、LAMP5是结直肠癌预后的独立预测因素,两者有希望成为结直肠癌的治疗靶点。
Objective To investigate the expression levels and prognostic value of transcription factor E-box binding to zinc finger protein 1(ZEB1)and lysosomal associated membrane protein 5(LAMP5)in colorectal cancer tissues.Methods A total of 120 colorectal cancer patients admitted to a hospital from January 2018 to January 2020 were selected.Immunohistochemical staining was performed on the colorectal cancer tissues and adjacent tissues of all patients,and the positivity rates of ZEB1 and LAMP5 were compared.The expression levels of ZEB1 and LAMP5 in colorectal cancer patients with different pathological characteristics were compared.All patients were followed up for 4 years and divided into two subgroups based on the follow-up results,namely the poor prognosis group(n=35)and the good prognosis group(n=85).The general clinical characteristics and expression levels of ZEB1 and LAMP5 were compared between the two groups.Logistic regression analysis was used to evaluate the predictive value of ZEB1 and LAMP5 for the prognosis of colorectal cancer.Results The relative expression level of ZEB 1 and LAMP 5 in colorectal cancer tissues [(38.26±5.49),(26.77±3.85)] and the positive rate of ZEB 1 and LAMP 5(86.67%,72.22%)were significantly higher than that of adjacent tissues [(15.46±2.54),(8.04±1.59),23.33%,15.56%],the contrast difference was statistically significant(t=41.280,χ2=25.437;t=49.255,χ 2 =16.071;P<0.05).Relative ZEBI expression levels in different TNM stages [I-Ⅱstage(35.55±4.13),Ⅲ-Ⅳstage(42.32±4.75)],lymph node metastasis[Yes(44.37±4.28),No(35.84±3.77)],degree of tumor differentiation [hypodifferentiated(35.27±4.57),and middle or high differentiated (29.04±2.55)],those differences were statistically significant(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001).The relative expression of LAMP 5 between different TNM stages [I-Ⅱstage(24.88±3.37),Ⅲ-Ⅳstage(29.61±2.57)],lymph node metastasis [yes(30.72±2.19),no(25.21±3.19)],degree of tumor differentiation [hypodifferentiated(24.57±3.62),and middle or high differentiated(29.04±2.55)],the contrast was statistically significant(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001).There were no differences in gender,age,gross type,and tumor size between the good prognosis group and the poor prognosis group(P>0.05),while there were differences in TNM stages,lymph node metastasis,tumor differentiation degrees,ratio of ZEB 1 and LAMP 5(P<0.05).Logistic regression analysis showed that TNM stage,lymph node metastasis,ZEB 1 positive,and LAMP 5 positive were independent predictive factors of poor prognosis in colorectal cancer(P<0.05).Conclusions ZEB1 and LAMP5 are highly expressed in colorectal cancer tissues and closely related to the occurrence and development of colorectal cancer.ZEB1 and LAMP5 are independent prognostic factors for colorectal cancer,and they have the potential to become therapeutic targets for colorectal cancer.