Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70456, Taiwan.
National Institute of Cancer Research, National Health Research Institutes, Zhunan 35053, Taiwan.
Aging (Albany NY). 2024 May 3;16(9):7889-7901. doi: 10.18632/aging.205791.
Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.
尽管新辅助放化疗(CRT)是治疗晚期直肠癌的既定标准,但临床结果仍不理想,需要确定预测生物标志物以做出更好的治疗决策。先前的研究表明 Fc 片段 IgG 结合蛋白(FCGBP)在各种癌症中具有致癌特性;然而,其在直肠癌中的临床意义尚不清楚。在这项研究中,我们首先对包含 46 名直肠癌患者的公共转录组进行了分析。在数据挖掘过程中关注细胞黏附,我们确定 为与 CRT 耐药性最相关的上调基因。随后,我们使用 343 个直肠癌组织块的免疫组织化学染色评估了 FCGBP 免疫强度。在治疗前,FCGBP 免疫强度升高与淋巴结受累相关(p = 0.001),治疗后肿瘤侵袭和淋巴结受累相关(均 p < 0.001),血管侵犯(p = 0.001),神经侵犯(p = 0.041),以及肿瘤消退减少(p < 0.001)。单因素分析显示,高 FCGBP 免疫表达与疾病特异性生存、局部无复发生存和无转移生存不良显著相关(均 p ≤ 0.0002)。此外,在多因素分析中,高 FCGBP 免疫表达独立成为所有三种生存结果的不利预后因素(均 p ≤ 0.025)。富集通路分析证实了 FCGBP 在赋予直肠癌对辐射抵抗中的作用。总之,我们的研究结果表明,直肠癌中 FCGBP 免疫表达升高与 CRT 反应不良和患者生存时间缩短显著相关。FCGBP 有望成为接受 CRT 的直肠癌患者有价值的预后生物标志物。