Abstract:
Background Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell Lung cancer. Previous studies have revealed various genetic and pathway alterations in lung squamous cell carcinoma. However, targeted therapy for LUSC has not yet been successful so far, and the treatment options are limited. Therefore, it is crucial to identify new targets to improve the survival prognosis of patients with LUSC.
Objective To explore the relationship between the expression of Histone deacetylase 11 (HDAC11) in tumor tissues and the clinicopathological characteristics of LUSC patients and its effect on prognosis.
Methods LUSC patients diagnosed at Tangdu Hospital of the Fourth Military Medical University from May 2009 to January 2014 were selected, and LUSC tissue and adjacent normal tissue samples were collected. Immunohistochemical staining was used to statistically analyze the expression of HDAC11 in these tissues. The survival status of the patients was followed up, and Kaplan-Meier survival curves were constructed to analyze the relationship between HDAC11 expression and the overall survival (OS) of LUSC patients. Furthermore, the data of LUSH cases in the GEPIA 2 database was utilized to further validate the association between HDAC11 gene and the survival and prognosis of LUSC patients, and related genes and proteins were also analyzed.
Results A total of 77 LUSC patients were enrolled. Pathological results showed that the expression of HDAC11 in LUSC tissues was higher than that in adjacent non-cancer tissues, and the difference was statistically significant (P<0.05). As of November 1, 2022, 50 patients had died, with an overall survival (OS) of 2.4 years for the patient cohort. LUSC patients with high expression of HDAC11 had poor median survival (1.9 95% CI: 1.7 - 3.3 yrs vs 3.2 95% CI: 2.7 - 4.0 yrs). Cox regression analysis showed that high HDAC11 expression was independently associated with risk of poor prognosis (HR=2.275, 95% CI: 1.256 - 4.120, P=0.007). Survival analysis of LUSC cases from the GEPIA 2 database also confirmed that HDAC11 expression was associated with OS (HR=1.709, 95% CI: 1.525 - 1.956). In addition, we identified genes with similar expression to HDAC11 in the GEPIA 2 database, which were involved in physiological processes such as cell migration and transport, and were significantly associated with oncogenes such as STAT3 and MDM2, which suggested that HDAC11 might affect tumorigenesis by regulating these genes.
Conclusion The high expression of HDAC11 is associated with the poor prognosis in LUSC patients, which is expected to become a new therapeutic target and efficacy evaluation standard for LUSC patients.