Squamous cell carcinoma antigen is a new member of the serine protease inhibitors

doi:10.1016/S0006-291X(05)81380-4

Biochemical and Biophysical Research Communications

Volume 181, Issue 1, 27 November 1991, Pages 51-58

https://doi.org/10.1016/S0006-291X(05)81380-4 Get rights and content

Summary

We have cloned cDNA of squamous cell carcinoma antigen. Sequence analysis of the complete 1711 basepairs SCC antigen cDNA revealed that it coded 390 amino acids and no typical signal sequence in the NH₂-terminus. Northern blot analysis of human squamous cell poly (A)⁺ RNA using this cDNA insert as the probe showed a single RNA species of about 1.7 kilobases. The cDNA was expressed in Escherichia coli and the product was detected by immunological methods using antibodies against SCC antigen, indicating that this cDNA encodes the entire SCC antigen sequence. The amino acid homology search revealed that SCC antigen was a member of the serine protease inhibitors family.

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Cited by (200)

The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma
2019, Auris Nasus Larynx
Citation Excerpt :
SCC antigen was first isolated biochemically from SCC tissue of the uterine cervix and is transcribed by two highly homologous genes, SCCA1 and SCCA2 [6,7]. These genes encode for members of the high molecular weight serine protease inhibitor (serpin) family [8]. Previous studies have shown that the mRNA copy number of SCCA2 was higher in malignant cervical tissues than in normal tissues [9], whereas SCCA1 protein is overexpressed in benign diseases, such as atopic dermatitis, bronchial asthma and sinonasal inverted papilloma [4,5,10,11].
The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC.
Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA.
Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15.
The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.
SERPINB3 and B4: From biochemistry to biology
2017, Seminars in Cell and Developmental Biology
Human SERPINB3 and SERPINB4 are evolutionary duplicated serine/cysteine protease inhibitors. Genomic analysis indicates that these paralogous genes were encoded from independent loci arising from tandem gene duplication. Although the two molecules share 92% identity of their amino acid sequences, they are distinct in the Reactive Center Loop (RCL) including a hinge region and catalytic sequences which accounts for altered substrate specificity. Elevated expression of the two molecules has been reported to contribute to numerous pathological conditions such as inflammatory diseases and cancer. In this review, we focus on summarizing the biochemical features of SERPINB3/B4 and discussing the mechanistic basis for their biological functions and implications in human diseases.
Squamous cell carcinoma antigen (SCC-Ag) during follow-up of cervical cancer patients: Role in the early diagnosis of recurrence
2016, Gynecologic Oncology
The aim of this study was to assess the potential benefit of routine squamous cell carcinoma antigen (SCC-Ag) assessment during follow-up of patients after treatment for early cervical cancer with regard to early diagnosis of cancer recurrence before clinical signs and symptoms occur.
All clinical, pathological, and serological data of patients referred to the Department of Gynecologic Oncology between July 1999 and June 2014, were retrospectively collected and analyzed. The SCC-Ag levels of 197 patients with diagnosis of stage I or II cervical squamous carcinoma, were performed.
In the univariate analysis, serum SCC-Ag was not significantly associated with grading (p = 0.85), LVSI (p = 0.95) and FIGO stage (p = 0.83) but it was significantly associated with recurrence of disease (p < 0.001). The Cox multivariate analyses showed that serum SCC-Ag level was an independent and statistically significant prognostic factor for OS and PFS. The median time interval between SCC-Ag test and diagnosis of recurrence were 0.3 and 1.8 months for positive and negative SCC-Ag groups respectively (p = 0.01). Considering patients with recurrence, no significant difference in terms of DFS and OS was found between women with high or low SCC-Ag levels.
Serum SCC-Ag reflects the response to treatment, and rising antigen levels often precede the clinical detection of recurrent disease, and may lead to early diagnosis. However such an advantage does not seem to improve the cure rate of patients with elevated SCC-Ag levels, most likely due to the lack of curative salvage treatments.
Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time?
2015, Clinica Chimica Acta
Citation Excerpt :
Recent molecular studies revealed that the squamous cell carcinoma antigen (SCCA) actually consists of two highly homologous proteins (SCCA1 and SCCA2) belonging to the serine protease inhibitors family. These proteins are encoded by two 1711 bp-long, tandemly arranged genes (SCCA1 and SCCA2) located on chromosome 18q21.3, and alternatively known as serpin peptidase inhibitor, clade B (ovalbumin), member 3 gene (SERPINB3) or serpin peptidase inhibitor, clade B (ovalbumin), member 4 gene (SERPINB4) [11]. These two genes, which share a high degree of homology (up to 98%), encode for two 45 kDa, 390 amino acid-long proteins of the same name, which are 92% identical at the amino acid level.
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third cause of cancer deaths. The leading predisposing condition is represented by an underlying viral hepatitis, mainly sustained by hepatitis B and C viruses. Since the cumulative risk of developing HCC can be as high as 30-fold in patients with infectious cirrhosis, a timely diagnosis is necessary for establishing an appropriate treatment in these patients. The armamentarium of diagnostic and prognostic biomarkers in patients with HCC currently entails alpha-fetoprotein (AFP) and a limited number of innovative biomarkers, among which squamous cell carcinoma antigen (SCCA) and its immune complexes are among the most widely investigated. The clinical data published so far and reviewed in this article seemingly suggest that neither total serum SSCA or its isoform 1 (i.e., SCCA1) may be ready for the prime time for management of patients with HCC. More interesting evidence has emerged from studies investigating the serum values of SCCA–IgM, since the diagnostic performance of this biomarker was found to be frequently superior to that of AFP and, even more importantly, the combination of SCCA–IgM and AFP was characterized by a much better sensitivity than either biomarker alone, with only a modest decrease of specificity. Larger studies are needed before these preliminary findings can be generalized, but the combined use of AFP and SCCA–IgM represents an appealing perspective in diagnosis and prognostication of HCC.
Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma
2023, Frontiers in Oncology
Role of squamous cell carcinoma antigen in prognostication, monitoring of treatment response, and surveillance of locally advanced cervical carcinoma
2023, Journal of Cancer Research and Therapeutics

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Squamous cell carcinoma antigen is a new member of the serine protease inhibitors

Summary

Am. J. Obstet. Gynecol.

Trends Biochem. Sci.

Anal. Biochem.

J. Biol. Chem.

Gene

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

Cancer

Gynecol. Obstet. Invest.

Cancer

Cancer

Cancer Res.

Nature