Sebzda Tadeusz, Karwacki Jakub, Cichoń Anna, Modrzejewska Katarzyna, Heimrath Jerzy, Łątka Mirosław, Gnus Jan, Gburek Jakub
Department of Pathophysiology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
Cancers (Basel). 2024 Jul 6;16(13):2471. doi: 10.3390/cancers16132471.
Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's -test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB ( = 0.04), LE ( = 0.01), and TSA ( = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival ( = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival ( = 0.041), notwithstanding ATA's lack of significance in univariate analysis ( = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.
结直肠癌（CRC）给全球医疗保健带来了沉重负担，在全球范围内导致了显著的发病率和死亡率。尽管筛查方法有所进步，但其发病率仍然很高，因此有必要继续努力进行早期检测和治疗。肿瘤侵袭和转移是结直肠癌致死率的主要决定因素，这凸显了理解其潜在机制以制定有效治疗策略的紧迫性。本研究旨在探讨血清生物标志物在预测CRC患者生存结局方面的潜力，重点关注组织蛋白酶B（CB）、白细胞弹性蛋白酶（LE）、总唾液酸（TSA）、脂质相关唾液酸（LASA）、抗胰蛋白酶活性（ATA）、C反应蛋白（CRP）和胱抑素C（CC）。我们招募了185例CRC患者和35名健康对照，评估了人口统计学变量、肿瘤特征以及7种血清生物标志物水平，包括（1）CB，（2）LE，（3）TSA，（4）LASA，（5）ATA，（6）CRP，和（7）CC。统计分析包括用于连续变量的方差分析（ANOVA）及Tukey事后检验和多变量方差分析（MANOVA）。配对样本使用学生t检验，而对于偏离正态分布的变量则应用非参数检验，如Mann-Whitney U检验和Wilcoxon符号秩检验。分类变量使用卡方检验和Kruskal-Wallis检验进行评估。使用Spearman等级相关系数来检验变量之间的相关性。生存分析采用Kaplan-Meier方法并进行对数秩检验以比较各组之间的生存时间。在CRC患者中，观察到CB（P = 0.04）、LE（P = 0.01）和TSA（P = 0.008）水平与生存结局之间存在显著关联。Dukes分期也与生存显示出显著相关性（P = 0.001）。然而，未发现LASA、ATA、CRP和CC有显著关联。对LE、TSA和ATA的多变量分析显示与生存有显著相关性（P = 0.041），尽管ATA在单变量分析中无显著性（P = 0.13）。CB、LE和TSA成为结直肠癌中有预后价值的有前景的诊断标志物，可能有助于早期诊断和治疗规划。需要进一步研究来验证这些发现并探索其他预后指标。
