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Small Cell Carcinomas of the Uterine Cervix and Lung: Proteomics Reveals Similar Protein Expression Profiles
  1. Tomomi Egawa-Takata, MD, PhD*,,
  2. Kiyoshi Yoshino, MD, PhD*,,
  3. Kosuke Hiramatsu, MD, PhD*,§,
  4. Satoshi Nakagawa, MD*,§,
  5. Satoshi Serada, PhD§,
  6. Aya Nakajima, MD, PhD,#,
  7. Hiroko Endo, PhD,
  8. Satoshi Kubota, MD*,,
  9. Shinya Matsuzaki, MD, PhD*,
  10. Eiji Kobayashi, MD, PhD*,
  11. Yutaka Ueda, MD, PhD*,
  12. Eiichi Morii, MD, PhD**,
  13. Masahiro Inoue, MD, PhD,††,
  14. Tetsuji Naka, MD, PhD§, and
  15. Tadashi Kimura, MD, PhD*
  1. *Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine;
  2. Department of Obstetrics and Gynecology, Osaka Police Hospital, Osaka;
  3. Department of Obstetrics and Gynecology, University Occupational and Environmental Health Japan, Fukuoka;
  4. §Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka;
  5. Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi;
  6. Department of Biochemistry, Osaka International Cancer Institute, Osaka;
  7. #Department of Radiation Therapy, Shiga Medical Center for Adults, Shiga;
  8. **Department of Pathology, Osaka University Graduate School of Medicine, Osaka;
  9. ††Department of Clinical Bio-Resource Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  1. Address correspondence and reprint requests to Tomomi Egawa-Takata, MD, PhD, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2–2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: takata{at}


Objective The phenotypic and pathological features of small cell cervical carcinoma (SMCC) and small small cell lung cancer (SCLC) are very similar; thus, the chemotherapy regimens used for the rare SMCC have been routinely based on regimens used for common SCLC. We set out to explore the protein expression profile similarities between these 2 cancers to prove that linking their therapeutic regimens is justified, with a secondary aim of finding tumor-specific proteins to use as additional biomarkers for more accurate diagnosis of SMCC, and potentially to use as therapeutic targets.

Methods Protein expression analysis was performed for 3 cases of SMCC and 1 example each of SCLC, mucinous adenocarcinoma of the cervix (MACC), lung mucinous adenocarcinoma (MACL), and squamous cell carcinoma of the cervix (SCC). We used cancer tissue–originated spheroids (CTOS) and isobaric tags for relative and absolute quantitation (iTRAQ)–based comprehensive and quantitative protein expression profile analysis. Expression in corresponding clinical samples was verified by immunohistochemistry.

Results Rather than organ of origin–specific patterns, the SMCC and SCLC samples revealed remarkably similar protein expression profiles—in agreement with their matching tumor pathology phenotypes. Sixteen proteins were expressed at least 2-fold higher in both small cell carcinomas (SMCC and SCLC) than in MACC or SCC. Immunohistochemical analysis confirmed higher expression of creatine kinase B-type in SMCC, compared with MACC and SCC.

Conclusions We demonstrate a significant overlapping similarity of protein expression profiles of lung and cervical small cell carcinomas despite the significant differences in their organs of origin.

  • Small cell carcinoma
  • Small cell lung cancer
  • Cervical cancer
  • iTRAQ
  • Cluster analysis

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  • This work was supported by MEXT KAKENHI (grant no. JP26861326) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

  • The authors declare no conflicts of interest.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.