PO.PS01.01 · 人群科学
RalA 和 RalB 在结直肠癌进展与生存中的作用
Contribution of RalA and RalB in colorectal cancer progression and survival
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：RalA 和 RalB 是 Ras 超家族成员，已被证实在多种癌症的肿瘤生长、侵袭和转移中发挥作用。然而，其在结直肠癌（CRC）中的蛋白水平表达及临床病理相关性，尤其是在南亚人群中，仍未得到充分描述。本研究旨在评估 CRC 肿瘤组织与配对正常组织中 RalA 和 RalB 的蛋白表达，并确定其与临床病理特征及患者生存的关联。
方法：经伦理批准后，从卡拉奇的阿迦汗大学医院共获取 123 例福尔马林固定石蜡包埋（FFPE）的 CRC 肿瘤样本和 43 例配对正常组织。构建组织芯片，并采用标准方案对 RalA 和 RalB 进行免疫组化。表达采用免疫反应评分（IRS；范围 0-9）进行量化。根据 IRS 中位数将患者分为高表达组和低表达组。采用 Spearman's rho 评估与临床病理参数的相关性。采用 Kaplan-Meier 曲线和 log-rank 检验评估与总生存期（OS）的关联。
结果：RalA 在肿瘤样本中表达升高，但无统计学意义（IRS 中位数 6 对 4；p = 0.499）。RalB 在肿瘤组织中显著高于正常组织（IRS 中位数 4 对 2；p = 0.028）。RalB 高表达与 OS 缩短密切相关（在 150 个月内从约 95% 下降至约 50%；log-rank p = 0.05），而 RalA 表达未显示出显著的预后效应（p = 0.428）。两种蛋白均与肿瘤分级呈显著负相关（RalA ρ = -0.316；RalB ρ = -0.310；p = 0.002），但与疾病分期、核周浸润和淋巴管侵犯无关联。
结论：与 RalA 相比，RalB 在结直肠肿瘤中显著上调，并可作为总生存期的强负性预后标志物。Ral 蛋白与肿瘤分级的负相关值得进一步研究。然而，这些发现支持 RalB 作为 CRC 中风险分层的潜在生物标志物及治疗靶点候选。
查看英文原文 English abstract
Background: RalA and RalB, members of the Ras superfamily, have been implicated in tumor growth, invasion, and metastasis across multiple cancers. However, their protein-level expression and clinicopathological relevance in colorectal cancer (CRC), particularly in South Asian populations, remain insufficiently characterized. This study aimed to evaluate RalA and RalB protein expression in CRC tumor versus matched normal tissues and to determine their associations with clinicopathological features and patient survival.
Methods: A total of 123 formalin-fixed paraffin-embedded (FFPE) CRC tumor samples and 43 matched normal tissues were obtained from the Aga Khan University Hospital, Karachi, following ethics approval. Tissue microarrays were constructed, and immunohistochemistry for RalA and RalB was performed using standard protocols. Expression was quantified using the Immunoreactivity Score (IRS; range 0-9). Patients were stratified into high- and low-expression groups based on median IRS. Correlations with clinicopathological parameters were assessed using Spearman's rho. Kaplan-Meier curves and log-rank tests evaluated associations with overall survival (OS).
Results: RalA expression was increased in tumor samples albeit not significantly (median IRS 6 vs. 4; p = 0.499). RalB was significantly higher in tumor tissue than in normal (median IRS 4 vs. 2; p = 0.028). High RalB expression was strongly associated with reduced OS (decline from ~95% to ~50% over 150 months; log-rank p = 0.05), whereas RalA expression showed no significant prognostic effect (p =0.428). Both proteins demonstrated significant negative correlations with tumor grade (RalA ρ = -0.316; RalB ρ = -0.310; p = 0.002), but no associations with disease stage, perinuclear invasion and lymph vascular invasion.
Conclusion: RalB, more than RalA, is significantly upregulated in colorectal tumors and serves as a strong negative prognostic marker for overall survival. The inverse correlation of Ral proteins with tumor grade warrants further investigation. However, these findings support RalB as a potential biomarker for risk stratification and as a candidate for therapeutic targeting in CRC.
利益披露 Disclosure
A. Shafiq, None..
N. Jan, None..
M. Rehman, None.