Abstract
ObjectiveTo investigate the clinical significance of the expression of MHC class I chain-related gene A (MICA) in patients with advanced non-small cell lung cancer and explore the relationship between MICA expression and the efficacy of cytokine-induced killer cell (CIK) therapy for treating advanced non-small cell lung cancer.MethodsWe obtained data on 222 patients with advanced non-small cell lung cancer, including data on MICA expression, age, gender, ECOG score, pathological type, stage, treatment history (including 38 patients who were given autologous CIK cell infusion), and overall survival (OS). MICA expression in lung cancer tissue was evaluated by immunohistochemical staining. Analyses of MICA expression, and CIK therapy association with survival outcomes were performed using Cox proportional models, Kaplan-Meier methods, and the log-rank test.Result s MICA was expressed in both membrane and cytoplasm. MICA expression correlated with the stage of lung cancer, ECOG score, gender and age. Multivariate COX regression analysis showed that the expression of MICA was an independent prognostic factor of advanced non-small cell lung cancer (p = 0.002). In subgroup analysis, we divided the 222 patients into CIK and control groups. In the CIK group, the medium OS (mOS) of patients with a high expression of MICA was longer than in those with low expression of MICA (27 months vs. 13 months). In the control group, the mOS in patients with a high expression of MICA was shorter than in patients with low MICA expression (9 months vs. 18 months). COX regression analysis showed that the MICA expression affects the effect of CIK therapy (p<0.0001).Conclusion1) The high expression of MICA is one of the indicators of a poor prognosis for advanced non-small cell lung cancer patients. 2) The high expression of MICA might be one of the predictive factors for successful CIK therapy.
Highlights
Lung cancer is still the leading cause of cancer-related mortality in the world, and about 1.4 million people are diagnosed with lung cancer every year [1]
They share similar structure to classical class I heavy chains, MHC class I chain-related gene A (MICA) and MICB do not associate with b2-microglobulin or with the transporter associated with antigen processing (TAP) [7]
Extracellular matrix, or nuclei was observed, whereas tumor infiltrating leukocytes stained positive for MICA (Figure 1)
Summary
Lung cancer is still the leading cause of cancer-related mortality in the world, and about 1.4 million people are diagnosed with lung cancer every year [1]. The theory of ‘‘immunoediting’’ has attempted to describe the complex interaction of a developing tumor with an evolving immune response. This is thought to include three phases; an elimination phase where the immune system destroys the tumor, an equilibrium phase where the tumor and immune system coexist, and an escape phase where the tumor evolves mechanisms to evade destruction by the immune system. The major histocompatibility complex class I chain-related (MIC) proteins represent a novel family of highly glycosylated, membraneanchored MHC class I-like molecules. They share similar structure to classical class I heavy chains, MICA and MICB do not associate with b2-microglobulin or with the transporter associated with antigen processing (TAP) [7].
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