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Basic Science
Expression and Humoral Response of A-Kinase Anchor Protein 4 in Cervical Cancer
  1. Sumit Agarwal, MSc*,
  2. Shikha Saini, MSc*,
  3. Deepak Parashar, MSc*,
  4. Archana Verma, MSc*,
  5. Nirmala Jagadish, PhD*,
  6. Aruna Batra, MD†,
  7. Sushma Suri, MD†,
  8. Amar Bhatnagar, MS‡,
  9. Anju Gupta, MD§,
  10. Abdul S. Ansari, PhD∥,
  11. Nirmal K. Lohiya, PhD∥ and
  12. Anil Suri, PhD*
  1. *Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg;
  2. †Department of Obstetrics and Gynecology, Safdarjung Hospital and Vardhman Mahavir Medical College;
  3. ‡Department of Cancer Surgery, Safdarjung Hospital and Vardhman Mahavir Medical College;
  4. §NMC Imaging and Diagnostic Centre, Vidyasagar Institute of Mental Health and Neuro-Sciences, New Delhi; and
  5. ∥Centre for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, India.
  1. Address correspondence and reprint requests to Anil Suri, PhD, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India. E-mail: anil@nii.res.in.

Abstract

Background Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer.

Methods In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA).

Findings Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades.

Conclusions Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.

  • AKAP4
  • Biomarker
  • Early detection and diagnosis
  • Immunotherapy
  • CT antigen

https://doi.org/10.1097/IGC.0b013e31828a0698

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    Footnotes

    • Shikha Saini has equal contribution as first author.

    • This work was supported by grants from Indo-UK Cancer Research Program, Centre for Molecular Medicine, NII-core funding, Department of Biotechnology, Government of India.

    • The authors declare no conflicts of interest.