Background/Objectives: Autophagy is a conserved self-degradation process by which cells break down and recycle their cellular constituents. This process is activated by various stressors, including nutrient deprivation and DNA damage, and has also been associated with tumor progression. In the present study, we aimed to determine the expression patterns, clinicopathological significance, and prognostic value of the autophagy marker microtubule-associated protein 1 light chain 3 alpha (LC3A)—an essential component of autophagic vacuoles—in rectal cancer.Methods: LC3A reactivity was measured by immunohistochemistry in tumor samples from 243 patients who underwent surgery for rectal cancer.Results: Three distinct patterns of LC3A expression were identified: diffuse cytoplasmic, perinuclear, and stone-like structures (SLS). In Kaplan–Meier survival analyses, patients positive for the SLS pattern of LC3A staining in the tumor periphery (TP) had worse overall survival (OS;p= 0.001) and disease-free survival (DFS;p= 0.030) than those without SLSs in this region, as determined by the log–rank test. When patients were stratified by tumor stage, this result was significant in those with stage T3–T4 (OS,p< 0.001; DFS,p= 0.001) but not T1–T2 disease. Multivariate Cox regression analysis further showed an association between TP-localized LC3A SLS positivity and reduced OS for the overall cohort (hazard ratio [HR] = 2.6313, 95% confidence interval [CI]: 1.090–6.349,p= 0.031) and specifically those in the T3–T4 subgroup (HR = 3.347, 95% CI: 1.657–6.760,p= 0.001).Conclusions: Our findings suggest that positivity for SLSs in the TP may hold clinical value as a biomarker for survival prognosis in rectal cancer patients.
背景/目的：自噬是一种保守的自我降解过程，细胞通过该过程分解并回收其细胞成分。这一过程由多种应激因素激活，包括营养剥夺和DNA损伤，并与肿瘤进展相关。本研究旨在探讨自噬标志物微管相关蛋白1轻链3α（LC3A）——自噬囊泡的关键组分——在直肠癌中的表达模式、临床病理学意义及预后价值。方法：通过免疫组织化学方法检测243例接受直肠癌手术患者的肿瘤样本中LC3A的反应性。结果：共识别出三种不同的LC3A表达模式：弥漫性胞质表达、核周表达及石样结构（SLS）。Kaplan-Meier生存分析显示，经对数秩检验证实，肿瘤周边区域（TP）存在LC3A染色SLS模式阳性的患者，其总生存期（OS；p=0.001）和无病生存期（DFS；p=0.030）均较该区域无SLS的患者更差。按肿瘤分期分层分析后，该结果在T3-T4期患者中具有显著性（OS，p<0.001；DFS，p=0.001），而在T1-T2期患者中不显著。多变量Cox回归分析进一步表明，TP区域LC3A SLS阳性与整体队列（风险比[HR]=2.6313，95%置信区间[CI]：1.090–6.349，p=0.031）及T3-T4亚组患者（HR=3.347，95% CI：1.657–6.760，p=0.001）的总生存期降低相关。结论：我们的研究结果表明，TP区域SLS阳性可能作为直肠癌患者生存预后的生物标志物具有临床价值。
Prognostic Value of LC3A Protein Expression Patterns in Rectal Cancer Tumors
肿瘤(癌症)患者之家