背景和目的:结直肠癌(CRC)是胃肠道系统最常见的恶性疾病,并且需要新的诊断和预后标志物来阐明完整的肿瘤谱。材料和方法:我们使用了43例患者的CRC肿瘤组织(Dukes\'A-D)和邻近的非癌组织。免疫组织化学用于检测磷酸二酯酶4B(PDE4B)的表达,磷酸二酯酶4D(PDE4D),和分泌的卷曲相关蛋白5(SFRP5)标记。我们还分析了PDE4B的表达水平,PDE4D,使用来自UCSCXena浏览器的RNA测序数据,与对照组织相比,CRC组织中的SFRP5。结果:在CRC阶段,PDE4B阳性细胞的分布各不相同,上皮和固有层之间的百分比不同。在健康对照组和所有CRC分期之间的PDE4B阳性上皮细胞数量存在统计学上的显着差异。以及不同的CRC阶段之间。同样,观察到健康对照和所有CRC分期之间固有层中PDE4B阳性细胞的数量存在显着差异,以及不同的CRC阶段之间。与CRCDukes'B阶段相比,CRCDukes'C阶段固有层中的PDE4B阳性细胞数量显着增加。健康对照和CRCDukes'A阶段之间的PDE4D阳性上皮细胞数量存在显着差异,B,D,以及在CRC阶段Dukes\'C和阶段A之间,B,与D.CRC阶段相比,Dukes\'A在固有层中的PDE4D阳性细胞明显多于D阶段。在健康对照和所有CRC阶段之间,固有层中的SFRP5阳性细胞数量也观察到显着差异。以及在CRC阶段Dukes\'A和D之间。虽然PDE4D的表达在CRC阶段之间有所不同,SFRP5的表达在上皮和固有层中始终保持强烈,主要在固有层出现显著差异。PDE4B的表达水平,PDE4D,和SFRP5揭示了CRC患者和健康对照之间这些基因表达的显着差异,对患者预后有显著影响。即,我们的结果表明PDE4B,PDE4D,与对照组织相比,和SFRP5在CRC组织中显著低表达。Kaplan-Meier生存分析和log-rank(Mantel-Cox)检验揭示了不同的预后意义,其中SFRP5表达水平较低的患者表现出明显更长的总生存期。数据与我们的免疫组织化学结果一致,可能表明这些基因在CRC中具有潜在的肿瘤抑制作用。结论:考虑到显著降低的基因表达,与我们在肿瘤组织中的免疫组织化学数据相比,对照组织,以及在其较高表达的情况下存活率明显较差,我们可以假设SFRP5是观察到的蛋白质中最有希望的CRC生物标志物。这些发现表明PDE4B的改变,PDE4D,和SFRP5在CRC进展过程中的表达,以及CRC的不同阶段之间,对理解CRC发生和进展的分子机制具有潜在的意义。
Background and Objectives: Colorectal cancer (CRC) is the most frequently diagnosed malignant disease of the gastrointestinal system, and new diagnostic and prognostic markers are needed to elucidate the complete tumor profile. Materials and Methods: We used CRC tumor tissues (Dukes\' A-D) and adjacent noncancerous tissues of 43 patients. Immunohistochemistry was used to examine the expression of phosphodiesterase 4B (PDE4B), phosphodiesterase 4D (PDE4D), and secreted frizzled related protein 5 (SFRP5) markers. We also analyzed the expression levels of PDE4B,
PDE4D, and SFRP5 in CRC tissues compared to control tissues using RNA-sequencing data from the UCSC Xena browser. Results: In CRC stages, the distribution of PDE4B-positive cells varied, with differing percentages between epithelium and lamina propria. Statistically significant differences were found in the number of PDE4B-positive epithelial cells between healthy controls and all CRC stages, as well as between different CRC stages. Similarly, significant differences were observed in the number of PDE4B-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between different CRC stages. CRC stage Dukes\' C exhibited a significantly higher number of PDE4B-positive cells in the lamina propria compared to CRC stage Dukes\' B. Significant differences were noted in the number of PDE4D-positive epithelial cells between healthy controls and CRC stages Dukes\' A, B, and D, as well as between CRC stage Dukes\' C and stages A, B, and D. CRC stage Dukes\' A had significantly more
PDE4D-positive cells in the lamina propria compared to stage D. Significant differences were also observed in the number of SFRP5-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between CRC stages Dukes\' A and D. While the expression of
PDE4D varied across CRC stages, the expression of SFRP5 remained consistently strong in both epithelium and lamina propria, with significant differences noted mainly in the lamina propria. The expression levels of PDE4B,
PDE4D, and SFRP5 reveal significant differences in the expression of these genes between CRC patients and healthy controls, with notable implications for patient prognosis. Namely, our results demonstrate that PDE4B,
PDE4D, and SFRP5 are significantly under-expressed in CRC tissues compared to control tissues. The Kaplan-Meier survival analysis and the log-rank (Mantel-Cox) test revealed distinct prognostic implications where patients with lower expression levels of SFRP5 exhibited significantly longer overall survival. The data align with our immunohistochemical results and might suggest a potential tumor-suppressive role for these genes in CRC. Conclusions: Considering significantly lower gene expression, aligned with our immunohistochemical data in tumor tissue in comparison to the control tissue, as well as the significantly poorer survival rate in the case of its higher expression, we can hypothesize that SFRP5 is the most promising biomarker for CRC out of the observed proteins. These findings suggest alterations in PDE4B, PDE4D, and SFRP5 expression during CRC progression, as well as between different stages of CRC, with potential implications for understanding the molecular mechanisms involved in CRC development and progression.