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Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma.
Shaikh, Soni; Basu, Sangramjit; Bag, Swarnendu; Chatterjee, Ankita; Datta, Sourav; Banerjee, Devmalya; Manikantan, Kapila; Arun, Indu; Arun, Pattatheyil; Biswas, Nidhan K; Maitra, Arindam; Mishra, Deepak Kumar; Majumder, Partha P; Dhar, Harsh; Mukherjee, Geetashree.
Afiliación
  • Shaikh S; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Basu S; Tata Consultancy Services (TCS), Kolkata, WB, India.
  • Bag S; Tata Translational Cancer Research Centre (TTCRC), 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Chatterjee A; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Datta S; CSIR-Institute of Genomics and Integrative Biology (IGIB), Mall Road, New Delhi, 110007, India.
  • Banerjee D; National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, WB, 741251, India.
  • Manikantan K; Narayana Superspeciality Hospital, 120, 1, Andul Rd, Shibpur, Howrah, WB, 711103, India.
  • Arun I; Medica Superspecialty Hospital, 127, Eastern Metropolitan Bypass, Nitai Nagar, Mukundapur, Kolkata, WB, 700099, India.
  • Arun P; Narayana Superspeciality Hospital, 120, 1, Andul Rd, Shibpur, Howrah, WB, 711103, India.
  • Biswas NK; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Maitra A; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Mishra DK; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
  • Majumder PP; National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, WB, 741251, India.
  • Dhar H; National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, WB, 741251, India.
  • Mukherjee G; Tata Medical Center, 14 MAR (E-W), New Town, Rajarhat, Kolkata, WB, 700160, India.
Sci Rep ; 14(1): 11609, 2024 05 21.
Article en En | MEDLINE | ID: mdl-38773214
ABSTRACT
No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.09% of tumor tissues and pyrimidine metabolism was active in GB-OSCC; these results correlated well with immunohistochemistry (IHC) and RNA sequencing data. Based on further gene and protein analyses, we proposed a pathway for the production of uracil in GB-OSCC tissues. Uridinetriphosphate (UTP) is hydrolyzed to uridine diphosphate (UDP) by CD39 in the tumor microenvironment (TME). We hypothesized that UDP enters the cell with the help of the UDP-specific P2Y6 receptor for further processing by ENTPD4/5 to produce uracil. As the ATP reserves diminish, the weakened immune cells in the TME utilize pyrimidine metabolism as fuel for antitumor activity, and the same mechanism is hijacked by the tumor cells to promote their survival. Correspondingly, the differential expression of ENTPD4 and ENTPD5 in immune and tumor cells, respectively, indicatedtheir involvement in disease progression. Furthermore, higher uracil levels were detected in patients with lymph node metastasis, indicating that metastatic potential is increased in the presence of uracil. The presence of uracil and/or expression patterns of intermediate molecules in purine and pyrimidine pathways, such asCD39, CD73, and P2Y6 receptors together with ENTPD4 and ENTPD5, hold promise as biomarker(s) for oral cancer diagnosis and prognosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Uracilo / Neoplasias de la Boca / Biomarcadores de Tumor Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Uracilo / Neoplasias de la Boca / Biomarcadores de Tumor Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Reino Unido