HDAC10 Is Positively Associated With PD-L1 Expression and Poor Prognosis in Patients With NSCLC

Abstract

Currently, non-small cell lung carcinoma (NSCLC) is a major worldwide health problem. Meanwhile accumulating evidence indicates that histone deacetylase (HDAC) activation could induce PD-L1 expression in various types of cancer, especially in myeloma and B-cell lymphomas. Therefore, we hypothesized that high-level expression of HDAC10 is associated with PD-L1 induction and poor prognosis in patients with NSCLC. In total 180 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection were enrolled from April 2004 to August 2009. The patients with integrated clinicopathological records were followed up. The expression level of HDAC10 and PD-L1 in tissue samples was determined by immunohistochemistry. We observed that HDAC10 expression in lung cancer tissue is significantly higher than that in corresponding paracancer tissue. Moreover, HDAC10 expression positively correlated with the expression level of PD-L1 (r = 0.213, P < 0.05) in NSCLC patients. Subgroup, multivariate analysis showed that the expression level of HDAC10 can be an independent prognostic factor and high-level expression of HDAC10 indicated poor overall survival for pulmonary carcinoma (r = 0.540, P < 0.001). Our findings suggest that the expression level of HDAC10 is positively associated with PD-L1 expression and may predict the outcome of patients with NSCLC.

Histone deacetylase 10, a potential epigenetic target for therapy

“…Up-regulated HDAC10 is associated with favorable overall survival (OS) in colon cancer, gastric cancer, RCC and NSCLC patients [ 31 , 92 , 98 , 99 ]. However, it should be noted that Liu et al [ 100 ] studied the OS data of 180 NSCLC patients and found that up-regulated HDAC10 predicted poor OS. Moreover, HDAC10 is also an independent predictor of treatment-free survival (TFS) as well.…”

“…PD-L1 is expressed in various cancers and its clinical therapeutic value has been validated [ 105 ]. Due to enhanced PD-L1 expression in NSCLC patients with high HDAC10 expression, HDAC10 could function as a biomarker for the evaluation of PD-L1 treatment [ 100 ]. The elevated radiosensitization caused by inhibiting HDAC10 involves down-regulation of Rad51a, a component of DNA repair pathways [ 106 ].…”

Characterization of Histone Deacetylase Mechanisms in Cancer Development

“…In addition, HDAC3 contributes to cell progression and proliferation by modulating the signal transducer and activator of transcription3 signalling pathway in liver cancers ( 152 ). Moreover, HDAC10 participates in G2/M transition by regulating the transcription of cyclin A2 protein depending on let-7 and HMGA2 ( 153 ). HDAC10 plays a crucial role in unchecked cell progression, since deletion of HDAC10 induces blockade at mitotic entry and thus restrains cell proliferation in human lung cancers ( 154 ).…”

“…Knocking down HDAC4 resulted in low levels of 53BP1 and inactivation of the DNA damage-induced G2 checkpoint ( 184 ). HDAC9 and HDAC10 were shown to play roles in homologous recombination ( 153 , 185 ). Furthermore, Doctor Zhang reported that the DNA mismatch repair protein MutS protein homologue 2 (MSH2) is associated with class IIb HDACs.…”

Unraveling the Epigenetic Role and Clinical Impact of Histone Deacetylases in Neoplasia

“…Although the role of multiple HDACis has been tested in non-small cell lung carcinoma (NSCLC), no significant research has been performed on correlations of HDAC isoforms with clinicopathological parameters and patient outcomes. Evidence from the various studies performed indicated that HDAC-1, -3, -5 and -10 were found to hold a significant role in the NSCLC progression [55][56][57][58][59][60][61] (Table 4). HDAC-1 mRNA was predominantly expressed in higher-stage (T3 or T4) lung cancer cases [55,58], and the strong HDAC-1 immunohistochemical expression (in terms of percentage and intensity) was associated with a remarkably poorer patient OS [55,58].…”