KIF2C is a prognostic biomarker associated with immune cell infiltration in breast cancer

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors

“…MAPK and JAK1/2 inhibitors, and STAT3 silencing, have led to S100A9 expression inhibition [44,46] but to our knowledge no direct link was yet established between Lapatinib and downregulation of S100A9 expression. The overexpression of KIF2C in many cancers has led to proliferation, EMT activation, invasion, and metastasis via PI3K/AKT, mTORC1, and MAPK/ERK signaling [47][48][49]. Due to its multifunctional role in cell cycle related processes and genomic stability, it was reported that the suppression of KIF2C inhibits mitosis [47].…”

“…As such, investigating the behavior of infiltrating immune cells under Lapatinib treatment or Lapatinib/immunotherapy combinations could lead to new and more effective therapeutic applications of Lapatinib. Lastly, both S100A9 and KIF2C, as being an integral part of the tumor microenvironment, have been reported as suitable markers for evaluating immunotherapy response [49][50][51].…”

“…Due to its multifunctional role in cell cycle related processes and genomic stability, it was reported that the suppression of KIF2C inhibits mitosis [47]. Yet, an important and less studied aspect is the involvement of KIF2C in immune responses, where the role of KIF2C in immune cell infiltration leading to tumor inhibition is either positively or negatively associated, depending on the cancer type [48,49]. Liu et al reported that in breast cancer increased expression of KIF2C is associated with higher immune cell infiltration [49].…”

“…Yet, an important and less studied aspect is the involvement of KIF2C in immune responses, where the role of KIF2C in immune cell infiltration leading to tumor inhibition is either positively or negatively associated, depending on the cancer type [48,49]. Liu et al reported that in breast cancer increased expression of KIF2C is associated with higher immune cell infiltration [49]. As such, investigating the behavior of infiltrating immune cells under Lapatinib treatment or Lapatinib/immunotherapy combinations could lead to new and more effective therapeutic applications of Lapatinib.…”

Differential whole-genome doubling based signatures for improvement on clinical outcomes and drug response in patients with breast cancer

“…The treatment of breast cancer is a long-term process, and patients can develop drug resistance over time, making it challenging to improve long-term survival rates [ 17 ]. Previous studies on molecular research in breast cancer have made significant contributions to clinical diagnosis and prognosis [ 18 ]. The heterogeneity of breast cancer subtypes has also been explained through various genomic events including large-scale somatic calls [ 19 ].…”