Medical Genetic Diagnosis and Therapy Center, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, Fujian, China.
World J Surg Oncol. 2024 Jan 20;22(1):22. doi: 10.1186/s12957-024-03301-z.
Transforming growth factor β (TGFβ) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFβ stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFβ stimulated genes in breast cancer.
TGFβ stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through "ESTIMATE" and "TIMER".
TGFBI was up-regulated by TGFβ treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFβ signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer.
TGFβ-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.
转化生长因子 β（TGFβ）是乳腺癌肺转移的关键调节因子，与乳腺癌的预后相关。然而，并非所有 TGFβ 刺激的基因在乳腺癌肺转移进展中都是功能性和预后性的。在本研究中，我们试图确定 TGFβ 刺激基因在乳腺癌中的预后。
通过基因表达微阵列鉴定 MDA-MB-231 细胞中的 TGFβ 刺激基因和 LM2-4175 细胞中的肺转移相关基因。通过生物信息学分析和组织微阵列验证来确定乳腺癌中诱导基因（TGFBI）的预后。通过“ESTIMATE”和“TIMER”确定乳腺癌的免疫浸润。
TGFBI 被 TGFβ 处理上调，并在 LM2-4175 细胞中过度表达。通过生物信息学分析，我们发现 TGFBI 的高表达与乳腺癌的肺转移无复发生存、无复发生存、无病生存和总生存时间缩短相关。此外，我们在 139 例中国乳腺癌患者中验证了 TGFBI 的预后。中国乳腺癌患者中 TGFBI 表达较高者总生存率较低。相应地，TGFBI 甲基化程度较高的乳腺癌患者总生存率较高。TGFBI 与乳腺癌中 TGFβ 信号通路和多种免疫相关信号通路的评分相关。乳腺癌中 TGFBI 的表达与基质评分、免疫评分和免疫细胞浸润也相关。
TGFβ 诱导的基因 TGFBI 与乳腺癌的预后和免疫浸润相关。
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