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| 结直肠癌组织中钙通道蛋白α2δ1表达与肿瘤相关成纤维细胞浸润的关系 |
| Relationship between calcitonin α2δ1 expression and carcinoma associated fibroblasts infiltration in colorectal cancer tissues |
| 投稿时间：2025-02-28 |
| DOI：10.3969/j.issn.1000-0399.2026.04.007 |
| 中文关键词: 结直肠癌 钙通道蛋白α2δ1 肿瘤相关成纤维细胞 预后doi:10.3969/j.issn.1000-0399.2026.04.007 |
| 英文关键词: Colorectal cancer Calcitonin α2δ1 Carcinoma-associated fibroblasts Prognosis |
| 基金项目:吕梁市重点研发项目（编号：2021SHFZ-2-43） |
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| 摘要点击次数: 364 |
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| 中文摘要: |
| 目的 探讨结直肠癌组织中钙通道蛋白α2δ1（CACNA2D1）表达与肿瘤相关成纤维细胞（CAFs）浸润的关系。方法 收集2020年1月至2022年6月吕梁市第一人民医院（山西医科大学附属吕梁医院）手术切除的98对结直肠癌组织及对应的癌旁组织，采用免疫组化检测直肠癌组织和癌旁组织中CACNA2D1、波形蛋白（Vimentin）、α-平滑肌肌动蛋白（α-SMA）的表达水平，计算CAFs阳性率；采用荧光定量聚合酶链式反应（PCR）检测CACNA2D1的mRNA表达水平，采用免疫印迹检测CACNA2D1及CAFs标志物α-SMA、成纤维细胞活化蛋白（FAP）的蛋白表达水平。分析CACNA2D1与CAFs及结直肠癌临床病理特征的关系，记录CACNA2D1高表达和低表达患者的随访生存结局（随访截止至患者死亡或2024年10月），分析结直肠癌预后的影响因素。结果 结直肠癌组织中CACNA2D1的蛋白高表达率、mRNA相对表达水平、蛋白相对表达水平均高于癌旁组织（P<0.05）；CACNA2D1高表达的结直肠癌患者淋巴结转移发生率、Ⅲ期比例均高于CACNA2D1低表达的结直肠癌患者（P<0.05）；CACNA2D1蛋白相对表达水平与CAFs阳性率、α-SMA和FAP的蛋白相对表达水平均呈正相关（r=0.385、0.423、0.371，P<0.05）。CACNA2D1高表达的结直肠癌组织中CAFs阳性率、α-SMA和FAP的蛋白相对表达水平均高于CACNA2D1低表达的结直肠癌组织；Cox回归分析结果显示，CACNA2D1表达水平、CAFs阳性率是结直肠癌的独立预后因素（P=0.007、0.018）。结论 结直肠癌组织中CACNA2D1表达增加与CAFs浸润增多相关，CACNA2D1表达及CAFs浸润共同影响结直肠癌的预后。 |
| 英文摘要: |
| Objective To investigate the relationship between calcium voltage-gated channel auxiliary subunit alpha 2/delta 1 (CACNA2D1) expression and carcinoma associated fibroblasts (CAFs) infiltration in colorectal cancer tissues. Methods A total of 98 pairs of colorectal cancer tissues and corresponding paracancer tissues resected in T the First People’s Hospital of Lyuliang by surgery during January 2020 to June 2022 were collected. The expression levels of CACNA2D1, Vimentin and α-smooth muscle actin (α-SMA) were detected by immunohistochemistry. CAFs positive rate was calculated by (number of α -SMA positive staining cells/number of Vimentin positive staining cells)×100%. The mRNA expression levels of CACNA2D1 were detected by fluorescence quantitative PCR. The protein expression levels of CACNA2D1 as well as CAFs markers α-SMA and fibroblast activation protein (FAP) were detected by Western blot. To analyze the relationship between CACNA2D1 and cancer-associated fibroblasts (CAFs) with clinical pathological features of colorectal cancer was anayzed; the to document follow-up survival outcomes in two patient cohorts (with follow-up ending at patient death or October 2024) were documented, and the to investigate prognostic factors influencing colorectal cancer outcomes were investigated. Results The protein high expression rate, mRNA relative expression level and protein relative expression level of CACNA2D1 in colorectal cancer tissues were higher than those in paracancer tissues (P<0.05). The incidence of lymph node metastasis and the proportion of stage Ⅲ of colorectal cancer patients with high expression of CACNA2D1 were higher than those with low expression of CACNA2D1 (P<0.05). Relative expression levels of the CACNA2D1 protein showed positive correlations with CAFs positivity rate and the relative expression levels of α-SMA and FAP proteins, with correlation coefficients of 0.385, 0.423, and 0.371, respectively (P<0.05) . The positive rate of CAFs and the protein relative expression levels of α-SMA and FAP in colorectal cancer tissues with high CACNA2D1 expression were higher than those in colorectal cancer tissues with low CACNA2D1 expression. Cox regression analysis showed that CACNA2D1 expression level and CAFs positive rate were independent prognostic factors for colorectal cancer (P=0.007、0.018). Conclusion Increased expression of CACNA2D1 in colorectal cancer tissues is associated with increased infiltration of CAFs, and the expression of CACNA2D1 and infiltration of CAFs jointly affect the prognosis of colorectal cancer. |
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