Neutrophils infiltration in the tongue squamous cell carcinoma and its correlation with CEACAM1 expression on tumor cells

PLoS One. 2014 Feb 27;9(2):e89991. doi: 10.1371/journal.pone.0089991. eCollection 2014.

Abstract

Objective: The present study aimed to explore the clinical significance of neutrophils infiltration and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) expression in the tongue squamous cell carcinoma (TSCC), and to probe the possible relationship between them.

Materials and methods: Tissue microarray and immunohistochemistry were used to detect neutrophils density and CEACAM1 expression in 74 cases of primary TSCC specimens and 17 cases of corresponding peritumoral tissues. The relationship of CEACAM1 expression and neutrophils density with clinicopathologic parameters and cancer-related survival of TSCC patients were evaluated. The correlation between CEACAM1 expression and neutrophils density was also evaluated. Real-time quantitative transcription polymerase chain reaction (qRT-PCR) was used to explore the possible molecular mechanisms between CEACAM1 expression and neutrophils infiltration.

Results: Immunohistochemistry evaluation revealed that there was more neutrophils infiltration in TSCC tissues than in peritumoral tissues. High neutrophil density was associated with LN metastasis (P=0.01), higher clinical stage (P=0.037) and tumor recurrence (P=0.024). CEACAM1 overexpression was also associated with lymph node metastasis (P=0.000) and higher clinical stage (P=0.001). Survival analysis revealed that both neutrophils infiltration and CEACAM1 overexpression were associated with poorer cancer-related survival of TSCC patients (P<0.05), and neutrophils infiltration was an independent prognostic factor for TSCC (P<0.05). Furthermore, overexpression of CEACAM1 was correlated with more neutrophils infiltration in TSCC tissues (P<0.01). qRT-PCR results showed that CEACAM1-4L can upregulate the mRNA expression of IL-8 and CXCL-6, which were strong chemotactic factors of neutrophils.

Conclusion: Our results demonstrated that more neutrophils infiltration and overexpression of CEACAM1 were associated with poor clinical outcomes in TSCC tissues. Overexpression of CEACAM1 on tumor cells correlated with more neutrophils infiltration to some extent through upregulating mRNA expression of IL-8 and CXCL-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Chemokine CCL2 / genetics
  • Chemokine CXCL6 / genetics
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / genetics
  • Lewis X Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neutrophil Infiltration*
  • Neutrophils / metabolism
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / pathology*
  • Transfection

Substances

  • Antigens, CD
  • CCL2 protein, human
  • CD66 antigens
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • Chemokine CXCL6
  • Interleukin-8
  • Lewis X Antigen

Grants and funding

This work is supported by the National Natural Science Foundation of China (No. 81072202, 31100650); China Postdoctoral Science Foundation (No. 2013M541922); Independent Innovation Foundation of Shandong University (No. 2012TS143); and the Scientific Research Foundation of Shandong Province of Outstanding Young Scientist Award (No. BS2013YY041). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.