Dek gene rearrangement in advanced stage squamous cell carcinoma of the lung the relationship with prognosis and immunotherapy treatment

Non-small cell lung carcinomas are the most common type of lung cancer. Squamous cell carcinoma, adenocarcinoma and large cell carcinoma constitute the majority of non-small cell lung carcinomas. Other types are seen less frequently. The most important parameter in prognosis and treatment in nonsmall cell lung carcinomas is the stage of the disease. While surgical resection is recommended for early-stage tumors, immunotherapy and treatments targeting the driver oncogene have come to the fore in recent years in addition to chemoradiotherapy for advanced-stage tumors. The discovery of specific targetable genetic changes suitable for therapeutic agents in non-small cell lung carcinomas has increased the importance of molecular diagnostic tests that detect these genetic changes by routine practice. Tyrosine kinase inhibitors targeting genetic changes in EGFR, ALK, ROS1, RET, BRAF V600E, MET Exon 14, and NTRK genes have been approved for certain subtypes of non-small cell carcinomas. United States Food and Drug Administration (FDA) for some subtypes of lung carcinomas has received approval. Recently, a new entity in the sinonasal region has been described as squamous cells containing DEK::AFF2 fusion. cell carcinomas are beginning to be identified. Head and neck area DEK::AFF2 nonkeratinizing squamous cell carcinomas have aggressive clinical behavior. However, its sensitivity to immunotherapy is limited in some HPV-negative carcinomas. It is a reported tumor [1, 2]. However, in squamous cell carcinomas of the lung, this gene is not detected. The number of relevant studies is very limited. The DEK gene is a potential biomarker and oncogene reported in many cancers. Until oncogene, transcriptional regulation, signal transduction, differentiation, apoptosis, RNA processing and the SAP domain to direct various important nuclear processes such as DNA replication. It binds to DNA. It has recently been revealed that increased expression of DEK protein is associated with a variety of neoplasms, including breast cancer, cervical cancer, neuroendocrine prostate cancer, hepatocellular carcinoma, hematological malignancies, gastric adenocarcinoma, and lung cancer. This suggests that DEK protein may be a potential biomarker and determinant for tumor progression and treatment. However, the role of protein in lung cancer is not fully known [3]. The AFF2 gene is an X-linked gene located on the long arm of the X chromosome (Xq28). This gene AFF gene including AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 belongs to his family. The AFF2 gene is expressed mainly in the brain and the protein encoded by synaptic. It plays a role in plasticity. AFF2 protein, an RNA that functions as a transcription activator binding protein. AFF2 rearrangements are associated with many malignant neoplasias [4]. On the other hand, therapeutic opportunities in thoracic malignancies have changed significantly with multiple phase III studies of immune checkpoint inhibitors in the treatment of advanced lung cancer. It is now possible to use immunotherapy over cytotoxic chemotherapy in at least a subgroup of patients. Its superiority has been proven. In addition, the combination of immunotherapy and chemotherapy in first-line. There is also evidence of the treatments used. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy, lung It has become an effective option in the treatment of cancer. There is also evidence of first-line treatments using a combination of immunotherapy and chemotherapy. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become an effective option in the treatment of lung cancer. Essentially, binding of PD-1 ligand to its receptors, PD-L1 or PD-L2, can prevent the innate cytotoxic T cell response against the tumor by inhibiting kinases involved in T cell activation [5]. Expression of PD-L1 protein in lung cancer is expected to be a prognostic factor or predict response to PD-1 blocking antibodies [6]. In this study, we evaluated fluorescence in situ in advanced squamous cell carcinoma of the lung. To determine the frequency of DEK rearrangement by hybridization technique (FISH), reverse transcriptase to identify cases with DEK:AFF2 fusion by polymerase chain reaction test (rt-PCR), The effect of gene alteration on prognosis, its relationship with PDL1 positivity and immunotherapy response. We planned to research. Our study included patients diagnosed with squamous cell carcinoma between 2017 and 2023 at Pamukkale University Faculty of Medicine, Department of Medical Pathology; We recruited 128 randomly selected patients from bronchoscopic biopsy or needle biopsy materials. DEK gene in all cases rearrangement, PD-L1 immunohistochemical expression and clinicopathological parameters and we examined the relationship between prognosis. We investigated the DEK::AFF2 fusion using the rt-PCR method and appropriate primers in 29 cases in which DEK gene rearrangement was detected. Ventana SP 263 clone was detected in all of our cases (n=128) by immunohistochemical method. We applied PD-L1 using Tumor proportion score (TPS) in tumor cells; PD-L1 15.8% cases with membranous staining below 1%, 62.4% cases with 1-50%, 50% with 21.8% of the cases were found to have staining. PD-L1 staining and gender, age, tumor diameter,between groups according to tumor stage, lymph node metastasis, distant metastasis, recurrence and death.No statistically significant difference was observed (p>0.05). Disease-free life with PD-L1 scoring. There was no statistically significant difference between duration and total survival (p>0.05). DEK rearrangement was investigated in all 128 cases included in the study using the FISH method.TEC rearrangement was detected in 21.8% of the patients. With DEK rearrangement, gender, age,tumor diameter, tumor stage, lymph node metastasis, distant metastasis, recurrence and survival status. No statistically significant difference was observed between them (p>0.05). DEK gene rearrangement positive and in terms of disease-free survival and total survival among negative cases. There was no statistically significant difference (p>0.05). rt-PCR using appropriate primers for 29 cases in which DEK rearrangement was detected by FISH method. DEK::AFF2 fusion was detected in all 29 cases. No statistically significant difference was observed between AFF2 fusion and gender, age, tumor diameter, tumor stage, lymph node metastasis, distant metastasis, recurrence and survival (p>0.05). There was no statistically significant difference in disease-free survival and total survival between AFF2 fusion positive and negative cases (p>0.05). PD-L1 expression is less than 1% in cases with DEK rearrangement/DEK::AFF2 fusion. The rate of being under was significantly higher (p:0.010; p<0.05). DEK protein is overexpressed in squamous cell carcinomas in many organs and it plays an active role in tumor initiation and maintenance. Although there are still many open questions regarding the regulation and function of this protein, high DEK protein expression may be useful as a novel prognostic factor and a new therapeutic target [7]. In conclusion, this is the first lung squamous cell carcinoma series in which DEK rearrangement/DEK::AFF2 fusion has been investigated. In addition, our study is a first in the literature, as the relationship between PD-L1 and DEK rearrangement/DEK::AFF2 fusion has never been compared in squamous cell carcinoma cases of the lung. We think that our findings may help in the selection of patients to receive immunotherapy, their prognosis, and to explain the pathogenesis of their squamous cell carcinomas.