Clinicopathological and prognostic importance of immunohistochemical CMTM6 and PD-L1 in non-small cell lung cancers

Lung cancer is the second most common cancer worldwide and the most common cause of cancer-related death. With the detection of immune checkpoints and the development of immunotherapy, promising developments have occurred in the treatment of lung cancer. The programmed death 1 ( PD-1) / programmed death ligand 1 ( PD-L1) pathway controls the initiation and maintenance of immune tolerance within the tumor microenvironment. CKLF- like MARVEL transmembrane domain containing 6 (CMTM6) is a type 3 transmembrane protein and acts as a PD-L1 protein regulator. In our study, 100 non-small cell lung carcinoma (NSCLC) cases diagnosed between 2015-2021 in the Department of Pathology of Meram Faculty of Medicine were evaluated. Immunohistochemical CMTM6 and PD-L1 stains were applied to the cases, and the data were statistically compared with clinicopathological parameters. Included in the study the median of the H-PD-L1 score of all patients was 10.00 (1st quartile: 0.00-3rd quartile: 70.00), and the median of the H-CMTM-6 score was 40.00 (1st quartile: 10.00-3rd quartile:100.00). The H-PD-L1 and H-CMTM6 scores of patients with tumor diameter ≥5 cm were statistically significantly higher than patients with tumor diameter <5 cm ( p=0.014, p=0.013). Both H-PD-L1 and H-CMTM6 scores of patients with histological type of adenocarcinoma were found to be statistically significantly lower than squamous cell carcinoma and other carcinoma types (p=0.004, p=0.001). For all NSCLC cases, H-PD-L1 and H-CMTM6 scores of Grade 1 patients were found to be statistically significantly lower than Grade 2 and Grade 3 patient groups (p=0.011, p=0.043). The H-PD-L1 score of the clinical stage 1 patients was found to be statistically significantly lower than the other stage (stage 2-3-4) patients (p=0.020). There was a good positive correlation between H-PD-L1 and H-CMTM6 scores (r=0.636, p<0.00 1). It was determined that patients with visceral pleural invasion had a 2,478 times (%95 GA=1,086-5,658, p=0,031) higher risk of death than patients without visceral pleura invasion, while patients with distant metastases had a 2.202 times (95% CI=1.026-4.727, p=0.043) higher risk of death than patients without distant metastasis. There are many studies on PD-L1 in the literature, and there is limited information on the regulation of PD-L1. In our study, a good positive correlation was found between H-PDL1 and H-CMTM6 scores. It is important to carry out more comprehensive studies in order to use CMTM6 as a prognostic marker or a therapeutic agent in lung cancer.