Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Abstract

New tools for diagnostic of HCC remain to further investigate. We have evaluated the expression of SCCA1, 2 mRNA and their prognostic value in hepatocellular carcinoma (HCC).Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing were performed to evaluate the mRNA expression of SCCA1 and SCCA2 in 93 HCCs, and 93 paired adjacent non-cancerous tissues (PNT), 16 cirrhosis livers and 9 normal livers. The correlation of SCCA variants expression with the clinical parameters and the factors affecting survival were analyzed statistically.Total SCCA was detected in 33.3% of HCCs (31/93), in 9.68% of PNT (9/93) and 22.2% of normal livers (2/9). No expression was found in cirrhosis livers (0/16). The frequencies of total SCCA expression were significantly higher in HCCs than that in PNT and liver cirrhosis (p = 0.000, 0.006). From mRNA sequencing of HCCs, a new SCCA1 variant (presenting a T357A mutation) was identified in 16 specimens, while wild type SCCA1 was identified in 11 specimens and SCCA2 in 27 specimens. Clinicopathological analysis showed that the frequency of SCCA1 was significantly higher in poorly differentiated HCC, compared with moderately and well differentiated tumors (p = 0.021). T357A variant has a significantly higher frequency in nonencapsulated tumors than wild type SCCA1 (p = 0.034).The SCCA1, 2 mRNA is effective for detecting HCC and could be potentially applied in HCC diagnosis. Key words: hepatocellular carcinoma, liver diseases, prognosis, squamous cell carcinoma antigenNeoplasma 61, 6, 2014 doi:10.4149/neo_2014_087 Liver cancer is the fifth most frequently diagnosed cancer but the second most frequent cause of cancer death in men worldwide (half of these cases and deaths are estimated to occur in China), and approximately, 70-85% of the total liver cancer are classified as hepatocellular carcinoma (HCC) [1]. Early detection enables us to provide the patients with more therapeutic options, which can improve survival rate of patients and reduce medical costs [2]. Despite the fact that serum AFP is still the golden standard amongst diagnostic markers for HCC, its diagnostic value is more and more questioned, because of its poor sensitivity and specificity [3,4]. Therefore, investigators are seeking for better HCC biomarkers.Squamous cell carcinoma antigen (SCCA), originally isolated from SCC tissue of the uterine cervix, is a member of the family of serine protease inhibitors [5]. The neutral and acidic isoforms of SCCA are encoded by 2 separate, but highly homologous genes, SCCA1 and SCCA2, at chromosome 18q21.3 [6]. Although SCCA1 and SCCA2 are with 91% identity at the amino acid concentration, they have distinct properties and substrate specificities. SCCA1 also known as SERPINB3, a papain-like cysteine proteinase inhibitor, inhibits cathepsins K, L and S [7]. SCCA2 also known as SERPINB4, a chymotrypsin-like serine proteinase inhibitor, inhibits proteolytic activity of endogenous cathepsin G and mast cell chymase [8]. The biological role of this serpin in carcinoge...

Salivary Scca1, Scca2 and Trop2 in Oral Cancer Patients—A Cross-Sectional Pilot Study

“…The majority of salivary SCCA1 values in the control group, both in UWS and SWS, were below the limit of detection of the ELISA kit. These results are in line with the allegation that SCCA1 is present in stratified squamous epithelium of healthy individuals but not in the circulation [7].…”

“…2022, 10, 70 2 of 10 isoform, inhibits the cysteine proteinases cathepsin K, L and S, while SCCA2 (SERPIN B4), the acidic isoform, inhibits the chymotrypsin-like proteinases, cathepsin G and mast cell chymase. Both SCCA1 and SCCA2 are present in the stratified squamous epithelium of healthy individuals and in squamous cell carcinomas, but not in the circulation of healthy individuals [7]. Mainly, SCCA2 is measurable and detected in the serum of patients with squamous cell carcinomas [10].…”

“…Squamous cell carcinoma antigen (SCCA) has been described in the literature as a diagnostic biomarker for squamous cell carcinomas of the uterine, cervix, hepatocellular, esophagus, lung, uterine cervix, head and neck cancer and colon [5][6][7][8] with the possibility of reflecting tumour stage, size, stromal, lymph node and vessel invasion and overall prognosis. Two genes, located at the 18q21.3, encode the two isoforms of SCCA [9].…”

Epitope-Specific Anti-SerpinB3 Antibodies for SerpinB3 Recognition and Biological Activity Inhibition

“…Originally discovered in 1970s by Kato and Torigoe in squamous cell carcinoma of the cervix, the SerpinB3/4 isoforms have been detected in the immune, nervous, muscular, secretory, and reproductive systems and in internal organs [6][7][8]. Upregulation of SB3/4 has been reported in several types of cancer [9][10][11][12][13][14][15][16][17][18]. Although it was initially reported that the two isoforms are cytosolic proteins, passively released from dying cells [19], additional cytoplasmic and nuclear localizations have been subsequently described [20].…”