Expression Of PD-L1 And CMTM6 Genes In Triple-negative Breast Cancer Malignancy And Its Clinical Significance

BackgroundTriple negative breast cancer(TNBC)has a poor prognosis,and systemic treatment options are limited.However,TNBC is more likely to receive immune control point suppression treatment than other sub-types of breast cancer due to its higher immunogenicity.PD-1/PD-L1 inhibitors can improve the therapeutic effect of TNBC patients,but some toxic and side effects still exist.CMTM6 is a chemokine-like factor containing the MARVEL transmembrane domain that involved vesicular transportation and membrane binding function.Studies have highlighted that CMTM6 in advanced NSCLC can stabilize PD-L1 and improve its immune suppressive effect.However,the role of CMTM6 in TNBC is not entirely clear,and further research is needed to assist in the selection and formulation of clinical treatment strategies.The screening of biomarkers that can predict the clinical benefits of PD-1/ PD-L1 inhibitors provides a certain theoretical basis for the realization of a clinical precision treatment.ObjectivesThis study detected the expression of CMTM6 and PD-L1 in TNBC patients,analyzed their relationship with prognosis,and explored the correlation between CMTM6 and PD-L1,in order to provide a basis for clinical treatment and medication.Methods1.We use Oncomine online tools to analyze the expression of CMTM6 and PD-L1 genes in breast cancer tissues and normal breast tissues,and conduct a meta-analysis of multiple sets of data from studies done by multiple institutions to count the relevant information of each sample.Then we use Graph Pad Prism5 to statistically analyze the data and make graphs.2.Linked Omics online tool was used to analyze the correlation between CMTM6 and PD-L1 and patient survival.We select tumor type as "Mammary gland malignancy",data type as "RNAseq",sample type as "ER Negative & PR Negative & HER2 Negative",target gene as "CMTM6" or "PD-L1",and target data type as " Clinical",select "Non-Parametric Test(Attribute Dependent)" as the statistical method.Then submit the analysis,view and download the analysis results.3.The GEPIA database was used to analyze the correlation between CMTM6 and PD-L1.4.We collected 52 breast cancer tissue specimens and 52 normal breast tissue specimens from February 2017 to February 2020 from the Affiliated Hospital of Huanghuai University,and further detected TNBC tissue samples by immunohistochemical staining and q RT-PCR The expression of CMTM6.Results1.Bioinformatics results: The expression levels of CMTM6 and PD-L1 in breast cancer tissues are higher than those in normal breast tissues(**P<0.01).In addition,the expression levels of CMTM6 and PD-L1 in TNBC tissues were higher than those in normal breast tissues(*P<0.05).2.Through bioinformatics analysis of survival time,it is found that the overall survival time of TNBC patients with high CMTM6 expression is significantly lower than that of TNBC patients who do not express CMTM6.We further analyzed PD-L1 and found that the overall survival of TNBC patients with high PD-L1 expression was lower than that of the non-expressing group.3.The online analysis tool GEPIA was used to detect the correlation between the CMTM6 gene and the PD-L1 gene.The results showed that the expression of the CMTM6 gene and PD-L1 gene was positively correlated(**P<0.01).4.Histological test results: We detected the expression of CMTM6 protein in breast cancer tissues by immunohistochemical staining.The results showed that the expression of CMTM6 in breast cancer tissues was significantly higher than that in normal breast tissues.At the same time,we performed q RT-PCR on the collected TNBC samples and found that the expression of CMTM6 in TNBC was significantly higher than that in normal tissues(***P < 0.001).We further used immunohistochemical staining and found that the expression of CMTM6 in TNBC tissue was also higher than that in normal tissues.ConclusionCMTM6 and PD-L1 are highly expressed in TNBC tissues,and are related to poor prognosis,and the two are positively correlated.The combined detection of CMTM6 and PD-L1 is of great significance for the treatment selection and prognosis evaluation of triple negative breast cancer.