2023 World Conference on Lung Cancer (Posters)-P1.24. Clinicopathological Characteristics of Pulmonary Squamous Cell Carcinoma with KDM5D Copy Number Loss

P1.24. Clinicopathological Characteristics of Pulmonary Squamous Cell Carcinoma with KDM5D Copy Number Loss - PDF(Abstract)

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This abstract is about a study that investigates the clinicopathological characteristics of pulmonary squamous cell carcinoma (SCC) with KDM5D copy number loss. KDM5D is a gene located on the Y chromosome and its loss defines a subset of cancer cells sensitive to ATR inhibition. The purpose of this study is to determine the frequency of KDM5D loss in lung SCCs and understand the characteristics of SCCs with KDM5D loss.<br /><br />The researchers evaluated KDM5D copy number loss in 174 surgically resected SCCs from males using fluorescence in situ hybridization (FISH). They also analyzed PD-L1 expression and oncogene alterations. In addition, they performed gene expression analysis and gene set enrichment analysis (GSEA) in a subset of 22 patients. Multiplexed fluorescent immunohistochemistry was used to examine the immune cell infiltration within tumors.<br /><br />The results showed that KDM5D copy number loss was detected in 43% of the SCC tumors. SCCs with KDM5D copy number loss were significantly associated with lymph node metastasis, late pathological stage, and high stromal content. There were no significant differences in other clinicopathological features between cases with and without KDM5D copy number loss.<br /><br />GSEA analysis revealed that up-regulated genes in tumors with KDM5D copy number loss were associated with cell division, while down-regulated genes were associated with immune response. Immunohistochemistry showed that CD8 and T-bet T cells infiltrated less in tumors with KDM5D copy number loss. Patients with KDM5D copy number loss tended to have worse overall survival and recurrence-free survival rates.<br /><br />In conclusion, the study found that approximately 40% of SCC in males exhibited KDM5D copy number loss, making them potentially sensitive to ATR inhibitors. The findings suggest that the DNA damage response pathway is a promising therapeutic target for lung cancer, especially for male patients with SCCs who do not have targetable genomic alterations.

Asset Subtitle

Takuo Hayashi

Meta Tag

Speaker Takuo Hayashi

Topic Pathology & Biomarkers: Prognostic Biomarkers

Keywords

pulmonary squamous cell carcinoma

KDM5D copy number loss

gene

Y chromosome

ATR inhibition

clinicopathological characteristics

frequency

lung SCCs

PD-L1 expression

oncogene alterations