KDM5D expression in lung carcinoma and its association with clinicopathologic parameters and survival

Globally, lung cancer is the most common malignancy among males, with higher incidence and mortality rates than in females. Sex chromosome analyses may provide insights into these disparities. KDM5D, located on the Y chromosome, is recognized as a tumor suppressor. Ongoing studies explore KDM5D's role in malignancies and therapeutic pathways. We evaluated the association of immunohistochemical expression with clinicopathologic parameters and survival.

A total of 102 male lung carcinoma patients who underwent trucut or resection procedures between June 1, 2014, and October 31, 2023, at a tertiary care center were analyzed. Evaluated parameters included age, tumor type, TNM stage, tumor-infiltrating lymphocytes, and KDM5D expression. Additional parameters were also assessed for resections. The JAD1D (KDM5D) antibody was applied to unstained slides, expression levels were quantified using the Q score method, and a cut-off was determined by the ROC curve.

A cut-off value of 8 was calculated for mortality, but no significant value was found for recurrence or progression. Patients with high expression (>8) had significantly lower overall survival. Higher levels were associated with increased maximum tumor diameter, involvement of pN1, M1 and above, stage IVA-IVB disease, and mild to moderate tumor-infiltrating lymphocytes. These features and elevated KDM5D were significantly higher in the exitus group.

KDM5D expression showed an unadjusted association with mortality in univariate Cox regression. However, this association was not significant after adjusting for clinicopathological variables or correcting for multiple comparisons. Given conflicting findings in the literature, further studies, methodological standardization, and deeper exploration of KDM5D and the KDM5 family are warranted.