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Twelve Serum Proteins Progressively Increase With Disease Stage in Squamous Cell Cervical Cancer Patients
  1. Wenbo Zhi, PhD*,,
  2. Daron Ferris, MD,
  3. Ashok Sharma, PhD*,
  4. Sharad Purohit, PhD*,
  5. Carlos Santos, MD§,
  6. Mingfang He, PhD*,,
  7. Sharad Ghamande, MD and
  8. Jin-Xiong She, PhD*,,
  1. *Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA;
  2. Sino-American Cancer Research Center and Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, Jiangsu Province, China;
  3. Department of Obstetrics and Gynecology, Cancer Center, Georgia Regents University, Augusta, GA; and
  4. §Department of Gynecologic Oncology, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
  1. Address correspondence and reprint requests to Jin-Xiong She, PhD, Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th St, Augusta, GA 30912. E-mail: jshe{at}


Objective This study aimed to reliably identify serum protein profile alterations that may be useful for elucidation of the disease mechanism and/or finding new targets for treatment and intervention.

Materials and Methods A total of 1057 women at 4 different squamous cell cervical cancer stages (noninvasive, invasive International Federation of Gynecology and Obstetrics stages I, II, and III) were included in this cross-sectional study. Forty-seven serum proteins were profiled using multiplex Luminex immunoassays.

Results Serum concentration of serum amyloid A (SAA), C-reactive protein (CRP), soluble tumor necrosis factor receptor I and II (sTNFRI and sTNFRII), soluble interleukin 2 receptor α (sIL2Rα), CXCL1, CXCL9, hepatocyte growth factor, squamous cell carcinoma antigen (SCCA), insulin-like growth factor binding protein 2, CA125, and carcinoembryonic antigen (CEA) were elevated significantly as disease progressed in cervical cancer patients. Serum levels are significantly different at early stage (I) for SAA, CRP, sIL2Rα, sTNFRII, SCCA, and CEA (P values ranged from 0.02 for CEA to 0.0001 for CRP and SCCA) and at late stages (II and III) for all 12 proteins (P values ranged from 8.78E-5 for CA125 to 3.49E-47 for SAA), as compared to the noninvasive stage. The areas under the curves of these proteins for disease state separation also improved with the advancement of the disease. The correlations between serum concentrations of these proteins also show different patterns at different clinical stages. These proteins are involved in multiple mechanisms including inflammation and immunity, angiogenesis, growth promotion, and metastasis.

Conclusions A number of serum proteins are significantly different between patients at different stages of cervical cancer.

  • Cervical cancer
  • Serum protein profile
  • Immunoassay
  • Inflammation
  • Angiogenesis

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  • This study was supported by a grant from the Georgia Cancer Coalition (Drs Ferris and She). Dr She was supported by the Georgia Research Alliance as an eminent scholar.

  • Wenbo Zhi, Daron Ferris, and Ashok Sharma contributed equally to the study.

  • The authors declare no conflicts of interest.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (