Xu Junming, Zhang Jinyan, Li Lei, Mao Jieqi, You Tiangeng, Li Yang
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University Shanghai, China.
Am J Transl Res. 2020 Dec 15;12(12):8162-8174. eCollection 2020.
The sex-determining region Y-box 12 (SOX12) is implicated in several oncogenic signaling pathways of multiple types of cancer; however, the biological effects of SOX12 on breast cancer has yet to be elucidated. Here, we assessed SOX12 expression using real-time quantitative PCR in 142 pairs of breast cancer and adjacent normal tissues (ANTs) and immunohistochemistry in 524 breast cancer and 147 ANTs. The effects of SOX12 on breast cancer progression, clinicopathological variables, and prognostic value were then investigated. SOX12 expression was markedly elevated in breast cancer tissues relative to that in ANTs at both mRNA and protein levels. Positive SOX12 expression was correlated to tumor size ( = 0.005), estrogen receptor (ER) ( = 0.018) and human epidermal growth factor receptor (HER2) ( = 0.004) status, lymph node metastasis ( < 0.001), and the tumor-node-metastasis (TNM) stage ( < 0.001). Notably, the positive rate of SOX12 expression gradually increased with breast cancer progression. Multivariate analysis indicated that SOX12 was an independent prognostic factor for overall survival (OS, = 0.023) and distant metastasis-free survival (DMFS, = 0.012). Subgroup analysis revealed that luminal and HER2 patients with positive SOX12 expression had a shorter OS period than those with negative SOX12 expression. Moreover, SOX12 expression was associated with a high risk of distant metastasis in invasive carcinoma with the lymph node metastasis subgroup. In summary, SOX12 correlates with progression and poor prognosis in human breast cancer, suggesting that SOX12 is a potential target for breast cancer treatment and warrants further functional research.
性别决定区Y盒12(SOX12)与多种类型癌症的多个致癌信号通路有关;然而,SOX12对乳腺癌的生物学影响尚未阐明。在此,我们通过实时定量PCR检测了142对乳腺癌组织和癌旁正常组织(ANTs)中SOX12的表达,并通过免疫组织化学检测了524例乳腺癌组织和147例ANTs中SOX12的表达。随后研究了SOX12对乳腺癌进展、临床病理变量和预后价值的影响。与ANTs相比,乳腺癌组织中SOX12在mRNA和蛋白质水平上均显著升高。SOX12阳性表达与肿瘤大小(P = 0.005)、雌激素受体(ER)(P = 0.018)和人表皮生长因子受体(HER2)(P = 0.004)状态、淋巴结转移(P < 0.001)以及肿瘤-淋巴结-转移(TNM)分期(P < 0.001)相关。值得注意的是,SOX12表达的阳性率随乳腺癌进展而逐渐升高。多变量分析表明,SOX12是总生存期(OS,P = 0.023)和无远处转移生存期(DMFS,P = 0.012)的独立预后因素。亚组分析显示,SOX12表达阳性的管腔型和HER2型患者的OS期短于SOX12表达阴性的患者。此外,在有淋巴结转移亚组的浸润性癌中,SOX12表达与远处转移的高风险相关。总之,SOX12与人乳腺癌的进展和不良预后相关,表明SOX12是乳腺癌治疗的潜在靶点,值得进一步进行功能研究。