Elevated expression of SerpinA1 and SerpinA3 in HLA‐positive cervical carcinoma

Abstract

In cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune elimination. To investigate this hypothesis, genome-wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial, and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defence response (n = 27) and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be up-regulated in HLA-positive tumours (3.6- and 8.2-fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). Thus, HLA-positive tumours are characterized by higher expression of genes associated with an inflammatory profile. In addition, expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA-positive tumours is associated with worse prognosis.

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

“…Recently, SerpinA1 and SerpinA3 have been shown to be overexpressed in tumors of a subpopulation of cervical cancer patients. In this study overexpression of these proteins correlated with a poorer survival [64]. Since SerpinA1 and SerpinA3 both have been implicated in inhibition of apoptosis [65,66], overexpression of these proteins may render the tumor cells insensitive for immune mediated apoptosis.…”

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

“…Previously, we have performed a cDNA microarray analysis on 32 tumor specimens. 32 All the cervical cancer samples examined in that study expressed versican (data not shown). In the present study, we have investigated the versican isoforms expressed in 20 tumor samples.…”

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…33 Furthermore, expression of SerpinA3 has been documented in lung adenocarcinoma 34 and in tandem with SerpinA1 in human leukocyte antigen-positive cervical carcinoma. 35 In this study, in an effort to discover novel biomarkers for the progression of cutaneous SCC, we analyzed expression of the entire serpin family in skin SCC cells using an oligonucleotide-based microarray technique. These results showed that SerpinA1 is markedly overexpressed in primary and metastatic cutaneous SCC cell lines compared with NHEKs.…”