Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology, Carson International Cancer Center, Shenzhen University Medical School, Shenzhen, Guangdong, 518055, China.
BMC Cancer. 2023 Apr 4;23(1):307. doi: 10.1186/s12885-023-10788-4.
The kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear.
The expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. The degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C.
KIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer.
KIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.
驱动蛋白-13 家族成员 2C（KIF2C）是一种多功能蛋白，参与多种生物学过程。KIF2C 在多种类型的癌症中频繁上调，与癌症的发生发展有关。然而，KIF2C 在肿瘤微环境免疫细胞浸润和乳腺癌免疫治疗中的作用尚不清楚。
利用肿瘤免疫估计资源（TIMER）数据库分析 KIF2C 的表达，并通过免疫组织化学染色在人乳腺癌组织中进一步验证。利用 TCGA 数据库、Kaplan-Meier 绘谱器、单变量和多变量 Cox 分析分别分析 KIF2C 表达与临床参数的相关性、KIF2C 对临床预后的影响和独立预后因素。根据独立预后因素构建列线图，并通过 C 指数、校准曲线、ROC 曲线和决策曲线分析进行验证。通过基因集富集分析（GSEA）探索 KIF2C 的潜在分子机制。利用 ESTIMATE 算法和单样本 GSEA（ssGSEA）评估肿瘤组织中基质和免疫细胞的浸润程度。利用肿瘤突变负担和肿瘤免疫功能障碍和排斥（TIDE）分析免疫治疗效率。最后，构建 KIF2C 相关竞争性内源 RNA（ceRNA）网络，预测 KIF2C 的潜在调控机制。
KIF2C 在 18 种不同类型的癌症中，包括乳腺癌，均显著上调。Kaplan-Meier 生存分析表明，高 KIF2C 表达与总生存期（OS）不良相关。KIF2C 表达与年龄、TMN 分期、T 状态和分子亚型等临床参数相关。我们确定年龄、分期、雌激素受体（ER）和 KIF2C 表达是乳腺癌 OS 相关的独立预后因素。基于这些独立预后因素开发了一个 OS 相关的列线图，该列线图对乳腺癌患者的 OS 具有良好的预测能力。最后，我们的结果表明，KIF2C 与乳腺癌患者的免疫细胞浸润、肿瘤突变负担和免疫治疗显著相关。
KIF2C 在乳腺癌中过度表达，与免疫细胞浸润和免疫治疗反应呈正相关。因此，KIF2C 可以作为乳腺癌预后和免疫治疗的潜在生物标志物。
