论著

血清乳酸脱氢酶在中晚期肝细胞癌靶向及免疫治疗中的预后预测价值研究

The prognostic value of serum lactate dehydrogenase level as a predictor of prognosis in targeted therapy and immunotherapy for advanced hepatocellular carcinoma

:446-452
 
      目的 探讨血清乳酸脱氢酶(LDH)在中晚期肝癌患者接受靶向联合免疫治疗后的预后预测价值。方法 选取2022年1月—2024年8月在莆田学院附属医院肿瘤内科经病理和影像学检查确诊的中晚期肝癌患者作为研究对象。从医院的电子病历系统中收集患者的基线资料,随访截止2025年8月,并记录随访结果,包括患者的疾病缓解情况和死亡情况,以及无疾病进展生存期(PFS)、总生存期(OS)。采用Kaplan-Meier方法绘制不同基线LDH水平患者的OS生存曲线,并通过Log-rank检验比较生存曲线。同时,运用多因素Cox比例风险回归分析探讨影响中晚期肝癌患者在接受靶向联合免疫治疗后OS的相关因素。结果 结果显示,在50例肝癌患者中,基线LDH低于200 U/L的有15例,而高于200 U/L的有35例。与基线LDH<200 U/L组相比,基线 LDH≥200 U/L患者PFS、OS更短,差异均有统计学意义(χ2分别为5.51、15.6,P值分别为0.019、0.017)。治疗8周后,与LDH降低患者相比,LDH升高患者OS更短,差异有统计学意义(χ2=13.2,P=0.04)。多因素Cox比例风险回归分析结果表明,基线LDH水平超过200 U/L是中晚期肝癌患者接受靶向联合免疫治疗后OS的影响因素[P=0.035,HR(95%CI)=5.03(1.12,22.54)]。结论 基线LDH水平较低的患者表现出更好的OS。基线LDH水平可以作为预测中晚期肝癌患者在接受靶向联合免疫治疗时预后的指标。 
   Objective To evaluate the prognostic significance of serum lactate dehydrogenase(LDH)levels in patients with advanced hepatocellular carcinoma(HCC)undergoing targeted therapy combined immunotherapy.Methods Patients diagnosed with advanced HCC were selected in Putian College Affiliated Hospital from January 2022 to August 2024,diagnosed with pathological and imaging examinations results.Patient baseline data were collected from the hospital’s electronic medical records,with follow-up extending until August 2025.We documented outcomes such as disease response and mortality,along with progression-free survival(PFS)and overall survival(OS).Kaplan-Meier survival curves were constructed based on baseline LDH levels,and the Log-rank test was employed for comparison.Additionally,multivariate Cox proportional hazards regression analysis was conducted to identify factors influencing OS in patients receiving targeted therapy combined immunotherapy.Results Among the 50 patients,15 had baseline LDH levels below 200 U/L,while 35 had levels above.Patients with baseline LDH≥200 U/L had significantly shorter PFS and OS than those with baseline LDH <200 U/L(χ2=5.51 and 15.6 for PFS and OS,respectively;P=0.019 and 0.017,respectively).After 8 weeks of treatment,patients with increased LDH had significantly shorter OS compared with patients with decreased LDH(χ2=13.2,P=0.04).Multivariate Cox proportional hazards regression analysis indicated that a baseline LDH level exceeding 200 U/L is an independent prognostic factor for OS in patients with intermediate to advanced HCC receiving targeted therapy combined with immunotherapy(P=0.035,HR 5.03[1.12,22.54]).Conclusions Patients with lower baseline LDH levels demonstrated better OS,suggesting that baseline LDH can serve as an important prognostic indicator for advanced HCC patients undergoing targeted combined immunotherapy.
论著

ZEB1、LAMP5在结直肠癌组织中的表达水平分析及预后预测价值分析

Expression levels and prognostic value of ZEB1 and LAMP5 in colorectal cancer tissues

:228-234
 
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,χ2=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,<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,χ2=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.
论著

ZEB1、LAMP5 在结直肠癌组织中的表达水平分析及预后预测价值分析

Expression levels and prognostic value of ZEB1 and LAMP5 in colorectal cancer tissues

:228-234
 
       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.
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