Expression Of MACC1 In Lung Adenocarcinoma And Its Correlation With Immune Cell Infiltration In TME

BackgroundsLung cancer is one of the most common malignant tumors worldwide,with lung adenocarcinoma as its main histological subtypes.In recent years,anti-PD-1/PD-Ll immunotherapy have been approved for the treatment of specific lung cancer patients,which greatly improved their survival.As we all know,anti-PD-1/PD-L1 therapy can block the immunosuppressive pathway in the tumor microenvironment(Tumor microenvironment,TME),which restores the anti-tumor immune response.In the TME,immune cell infiltration is a common feature,which includes tumor-related lymphocytes such as T lymphocytes,B lymphocytes,tumor-associated macrophages and natural killer cells.The type,number and location of these immune cells are closely related to the immune status of tumors,which play a key role in tumorigenesis,tumor development and the outcome of patients with lung cancer.Therefore,further study is needed to characterize the level of immune cell infiltration and the regulatory factors of its function in the tumor microenvironment of lung cancer.MACC1(metastasis-associated in colon cancer 1)gene has been found to contributed to the development of many tumors,such as colon cancer and liver cancer.Studies have discovered that MACC1 had a great predictive significance for the prognosis of lung cancer.The subgroup with elevated MACC1 expression has a higher postoperative recurrence rate and a poorer survival.It remains unclear whether the level of MACC1 in lung adenocarcinoma affects the immune cell infiltration in the tumor microenvironment.ObjectiveTo evaluate the correlation between MACC1 and the tumor microenvironment of lung adenocarcinoma,this article analyzed the correlation between MACC1 and the clinicopathological characteristics of lung adenocarcinoma,and explored the influence of MACC1 on the infiltration of various immune cells in the TME of lung adenocarcinoma.MethodsTo assess the expression of MACC1 in a variety of tumors,the mRNA expression profile and the corresponding clinical data and survival data were downloaded from the TCGA database.And the expression of MACC1 in multiple tumors,incuding lung adenocarcinoma,and its clinical relevance were further investigated.The gene expression data of lung adenocarcinoma from TCGA was divided into two groups based on the expression of MACC1.Using the online tool ImmuneCell AI,the infiltration of 18 T cell subsets and 6 other types of immune cells(B cells,NK cells,monocytes,macrophages,neutrophils and DC cells)was scored.And the influence of MACC1 expression level on the infiltration of different immune cells was analyzed.Lung adenocarcinoma tissues and matched normal lung tissues were collected from patients who underwent surgery and analyzed for the expression of MACC1 and CD8a by immunohistochemistry.The demographic data,diagnostic information and followup information of the corresponding patients were also collected.Then,we studied the relationship between the expression of MACC1,clinical-pathological features and the level of tumor infiltrating CD8+T cells in the TME.Results(1)TCGA:MACC1 was significantly upregulated(P<0.05)in many malignant tumors.Patients with high levels of MACC1 have a shorter overall survival(P<0.05).The gene expression data of lung adenocarcinoma and its paired normal tissues also suggested that MACC1 was up-regulated in lung adenocarcinoma(P<0.05).(2)IHC:Compared with normal lung tissue,the expression of MACC1 was significantly increased(P<0.05)in lung adenocarcinoma tissue;MACC1 expression intensity was significantly correlated with the patient’s tumor stage and lymph node metastasis(P<0.05).(3)The immune infiltration profiles showed that the infiltration of CD8+T lymphocytes,NK cells,cytotoxic T cells,Th1 cells,and neutrophils decreased dramatically,while CD4+T lymphocytes and DC cells increased in lung adenocarcinoma with higher MACC1 expression(P<0.05).IHC-based assays also confirmed that the density tumor infiltrating CD8+T cells was negatively correlated with the expression of MACC1.Conclusions(1)MACC1 is upregulated in most tumors.High expression of MACC1 was associated with poor prognosis;(2)MACC1 expression is significantly upregulated in lung adenocarcinoma;MACC1 expression intensity is positively correlated with the patient’s tumor stage and lymph node metastasis.(3)The expression level of MACC1 is correlated with different levels of immune cell infiltration.It may affect the development of tumors by shaping the pattern of tumor immune landscape.