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Standardized Uptake Value for 18F-Fluorodeoxyglucose Is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer.
Floberg, John M; Zhang, Jin; Muhammad, Naoshad; DeWees, Todd A; Inkman, Matthew; Chen, Kevin; Lin, Alexander J; Rashmi, Ramachandran; Jayachandran, Kay; Edelson, Brian T; Siegel, Barry A; Dehdashti, Farrokh; Grigsby, Perry W; Markovina, Stephanie; Schwarz, Julie K.
Afiliación
  • Floberg JM; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Zhang J; Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Muhammad N; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • DeWees TA; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Inkman M; Division of Biomedical Statistics and Informatics, Mayo Clinic, Phoenix, Arizona.
  • Chen K; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Lin AJ; Washington University School of Medicine, St. Louis, Missouri.
  • Rashmi R; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Jayachandran K; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Edelson BT; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
  • Siegel BA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
  • Dehdashti F; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
  • Grigsby PW; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
  • Markovina S; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
  • Schwarz JK; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Clin Cancer Res ; 27(15): 4245-4255, 2021 08 01.
Article en En | MEDLINE | ID: mdl-33820781
PURPOSE: Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers. EXPERIMENTAL DESIGN: An SUVmax most prognostic for freedom from progression (FFP) was identified and compared with known prognostic clinical variables in a cohort of 318 patients treated with definitive radiation with prospectively collected clinical data. Gene set enrichment analysis (GSEA) and CIBERSORT of whole-transcriptome data from 68 patients were used to identify biological pathways and immune cell subpopulations associated with high SUVmax. IHC using a tissue microarray (TMA, N = 82) was used to validate the CIBERSORT findings. The impact of macrophages on cervical cancer glucose metabolism was investigated in coculture experiments. RESULTS: SUVmax <11.4 was most prognostic for FFP (P = 0.001). The GSEA showed that high SUVmax is associated with increased gene expression of inflammatory pathways, including JAK/STAT3 signaling. CIBERSORT and CD68 staining of the TMA showed high SUVmax tumors are characterized by a monocyte-predominant immune infiltrate. Coculture of cervical cancer cells with macrophages or macrophage-conditioned media altered glucose uptake, and IL6 and JAK/STAT3 signaling contribute to this effect. CONCLUSIONS: SUVmax is a prognostic marker in cervical cancer that is associated with activation of inflammatory pathways and tumor infiltration of myeloid-derived immune cells, particularly macrophages. Macrophages contribute to changes in cervical cancer glucose metabolism.See related commentary by Williamson et al., p. 4136.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / Radiofármacos / Fluorodesoxiglucosa F18 / Tomografía de Emisión de Positrones Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / Radiofármacos / Fluorodesoxiglucosa F18 / Tomografía de Emisión de Positrones Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos