Academic Unit of Surgery, School of Medicine, University of Glasgow, Royal Infirmary, Alexandria Parade, Glasgow, United Kingdom.
Unit of Molecular Pathology, School of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garscube Estate, Glasgow, United Kingdom.
Histol Histopathol. 2024 Feb;39(2):177-200. doi: 10.14670/HH-18-655. Epub 2023 Jul 31.
Prognostic significance and gene signatures associated with carbonic anhydrase IX (CAIX) was investigated in triple negative breast cancer (TNBC) patients.
Immunohistochemistry (IHC) for CAIX was performed in tissue microarrays (TMAs) of 136 TNBC patients. In a subset of 52 patients Digital Spatial Profiler (DSP) was performed in tumour (pan-cytokeratin+) and stroma (pan-cytokeratin-). Differentially expressed genes (DEGs) with P<0.05 and and log2 fold change (FC)>(±0.25 and ±0.3, for tumour and stromal compartment, respectively) were identified. Four genes were validated at the protein level.
Cytoplasmic CAIX expression was independently associated with poor recurrence free survival in TNBC patients [hazard ratio (HR)=6.59, 95% confidence interval (CI): 1.47-29.58, P=0.014]. DEG analysis identified 4 up-regulated genes (CD68, HIF1A, pan-melanocyte, and VSIR) in the tumour region and 9 down-regulated genes in the stromal region (CD86, CD3E, MS4A1, BCL2, CCL5, NKG7, PTPRC, CD27, and FAS) when low versus high CAIX expression was explored. Employing IHC, high CD68 and HIF-1α was associated with poorer prognosis and high BCL2 and CD3 was associated with good prognosis.
DSP technology identified DEGs in TNBC. Selected genes validated by IHC showed involvement of CD3 and BCL2 expression within stroma and HIF-1α, and CD68 expression within tumour. However, further functional analysis is warranted.
研究碳酸酐酶 IX（CAIX）与三阴性乳腺癌（TNBC）患者的预后意义和基因特征。
对 136 例 TNBC 患者的组织微阵列（TMA）进行 CAIX 的免疫组织化学（IHC）检测。在 52 例患者的肿瘤（泛细胞角蛋白+）和基质（泛细胞角蛋白-）中进行了数字空间分析器（DSP）。鉴定出差异表达基因（DEGs），P 值<0.05，对数倍数变化（FC）＞（±0.25 和 ±0.3，分别为肿瘤和基质区）。在蛋白水平上验证了 4 个基因。
细胞质 CAIX 的表达与 TNBC 患者无复发生存率独立相关[风险比（HR）=6.59，95%置信区间（CI）：1.47-29.58，P=0.014]。DEG 分析在肿瘤区域中发现了 4 个上调基因（CD68、HIF1A、泛黑色素细胞和 VSIR）和 9 个下调基因在基质区域（CD86、CD3E、MS4A1、BCL2、CCL5、NKG7、PTPRC、CD27 和 FAS）中，当低 CAIX 表达与高 CAIX 表达比较时。采用 IHC，高 CD68 和 HIF-1α与预后不良相关，而高 BCL2 和 CD3 与预后良好相关。
DSP 技术鉴定了 TNBC 中的 DEGs。通过 IHC 验证的选定基因显示 CD3 和 BCL2 表达与基质有关，HIF-1α和 CD68 表达与肿瘤有关。然而，还需要进一步的功能分析。
