Wang Zhi, Wu Di, Dong Menglu, Xia Yu, Xu Tao
Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.
Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of HUST, Wuhan, China.
Transl Cancer Res. 2021 Jan;10(1):261-272. doi: 10.21037/tcr-20-2099.
Annually, breast cancer (BC) is the most common newly diagnosed cancer in females. The relatively crude measures of the molecular phenotypes of BC have not provided a comprehensive understanding of its molecular architecture. To a certain extent, this has resulted in many patients being over- or undertreated. Therefore, novel biomarkers that help to improve patients' outcomes are required. The potassium channel tetramerization domain containing 12 (KCTD12) is one such candidate.
Ribonucleic acid-sequencing (RNA-Seq) filings along with corresponding clinical information of BC samples were obtained from The Cancer Genome Atlas (TCGA) program databases to evaluate the associations between KCTD12 expression levels and clinical features. The prognostic value of KCTD12 in patients was examined by Kaplan-Meier survival analysis and PrognoScan database analysis. To identify the main functions of KCTD12 in BC, we performed gene set enrichment analysis (GSEA) in BC samples and cell lines. The correlations between KCTD12 expression and tumor-infiltrating lymphocyte quantities was confirmed using two online tools: Tumor Immune Estimation Resource and the Gene Expression Profiling Interaction Analysis 2.
KCTD12 expression was significantly decreased in cancer samples compared to normal samples, and was lowly expressed in aggressive disease relative to initial disease. Patients with lower KCTD12 expression levels showed a shorter overall survival and a shorter recurrence-free survival, indicating a worse prognosis. We found that genes of BC in the high-KCTD12 expression group were enriched in immune response pathways. Finally, the positive correlations between the expression of tumor-infiltrating lymphocytes, programmed cell-death ligand 1 (PD-L1), and programmed cell-death protein 1 (PD-1), and KCTD12 expression were confirmed.
KCTD12 can be considered a biomarker to predict the prognosis of BC patients. KCTD12 may also help to predict patient response to PD-L1 or PD-1 inhibitor treatment.
乳腺癌（BC）是女性每年新诊断出的最常见癌症。对BC分子表型的相对粗略测量未能全面了解其分子结构。在一定程度上，这导致许多患者接受了过度治疗或治疗不足。因此，需要有助于改善患者预后的新型生物标志物。含钾通道四聚化结构域12（KCTD12）就是这样一个候选标志物。
从癌症基因组图谱（TCGA）项目数据库中获取BC样本的核糖核酸测序（RNA-Seq）文件及相应临床信息，以评估KCTD12表达水平与临床特征之间的关联。通过Kaplan-Meier生存分析和PrognoScan数据库分析来检验KCTD12对患者的预后价值。为确定KCTD12在BC中的主要功能，我们在BC样本和细胞系中进行了基因集富集分析（GSEA）。使用两个在线工具：肿瘤免疫估计资源和基因表达谱相互作用分析2，确认了KCTD12表达与肿瘤浸润淋巴细胞数量之间的相关性。
与正常样本相比，癌症样本中KCTD12表达显著降低，相对于早期疾病，侵袭性疾病中KCTD12表达较低。KCTD12表达水平较低的患者总生存期较短，无复发生存期也较短，表明预后较差。我们发现高KCTD12表达组中BC的基因在免疫反应途径中富集。最后，确认了肿瘤浸润淋巴细胞、程序性细胞死亡配体1（PD-L1）和程序性细胞死亡蛋白1（PD-1）的表达与KCTD12表达之间呈正相关。
KCTD12可被视为预测BC患者预后的生物标志物。KCTD12也可能有助于预测患者对PD-L1或PD-1抑制剂治疗的反应。
