Alpha-1-antichymotrypsin expression in lung adenocarcinoma and its possible association with tumor progression

Abstract

Background. Alpha‐1‐antichymotrypsin (ACT) is a serine protease inhibitor, expression of which has been shown in various tumor types, but its biologic and clinical implications in tumor tissues are obscure. The authors examined ACT expression in lung adenocarcinoma to determine its clinicopathologic and prognostic significance. Methods. First, reverse transcriptase–polymerase chain reaction (RT–PCR) using oligonucleotide primers specific for ACT and Western blotting and immunohistochemical methods using anti‐ACT antibodies were performed in several lung adenocarcinoma cell lines. Secondly, ACT expression in clinical materials was examined immunohistochemically. Results. By RT–PCR, Western blotting, and immunohistochemical methods, ACT synthesis was confirmed in several lung adenocarcinoma cell lines. Seventy‐five (52%) of 170 surgically resected lung adenocarcinomas showed positive staining for ACT mainly in the cytoplasm, and the incidence of ACT expression was significantly higher in advanced T classification tumors (P = 0.009) or large sized tumors (P = 0.004). Tumors with a higher rate of mitosis were significantly positive for ACT expression (P = 0.023). Patients with ACT‐positive adenocarcinoma had a shorter disease free survival (DFS) and a poor prognosis compared with those who were ACT–negative, most significantly among Stage I tumors (DFS, P = 0.003; overall survival, P = 0.006). In a multivariate analysis, the P value of ACT expression status in Stage I tumors was marginally significant (overall survival, P = 0.058). Conclusions. These results using cell lines suggest the potential productivity of ACT by lung adenocarcinoma cells. The data in clinical materials, combined with results of the previous report that ACT in breast cancer acts as a minor growth factor‐like substance, suggest that ACT expression in lung adenocarcinoma also may be associated closely with tumor progression and especially with tumor growth. Alpha‐1‐antichymotrypsin expression status in Stage I tumors may be a potential independent prognostic factor.

Comparative analysis of the human urinary proteome by 1D SDS-PAGE and chip-HPLC-MS/MS identification of the AACT putative urinary biomarker

“…By RT-PCR, western blotting, and immunohistochemical methods, AACT synthesis were confirmed in several lung adenocarcinoma cell lines and surgically resected lung adenocarcinomas tissues. The data in clinical materials, combined with results of the previous report that AACT in breast cancer acts as a minor growth factor-like substance, suggested that AACT expression in lung adenocarcinoma also may be associated closely with tumor progression and especially with tumor growth [24]. Combined with our finding, we strongly proposed AACT to be a candidate biomarker for objective and non-invasive diagnosis of NSCLC in urine.…”

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

“…32 Elevated levels of AAT have been detected in the serum of patients with SCC of the oral cavity. 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.…”

Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast Cancer

“…AAT is known to down regulate tumor necrosis factor-induced apoptosis, elevated levels may therefore promote cell survival and growth of tumors [30]. AACT expression in lung adenocarcinomas was significantly higher in advanced tumors with a higher rate of mitosis [31], and was inversely correlated with shorter disease free survival (DFS) and prognosis. Both Higashiyama, et al [31], and Laursen and Lykkesfeldt [32] concluded that AACT acts as a minor growth factor-like substance in breast cancer, in concordance with its association of poor prognosis in breast cancer patients.…”