RESUMEN
BACKGROUND: This study aims to assess Plakophilin-3 (PKP3) as a surrogate biomarker of circulating tumor cells in patients with gastrointestinal cancer. METHODS: The primary aim is to estimate the diagnostic accuracy of PKP3 real-time reverse transcriptase-PCR in blood. Receiver operating characteristic curves were constructed. Correlations between the blood PKP3 levels and the clinicopathologic features of the study subjects were analyzed. Logistic regression was used to predict outcomes based on PKP3. RESULTS: Sixty-four patients with gastrointestinal cancer and 23 controls were included. The mean relative PKP3 mRNA expression was 48.45 in cancer patients and 2.8 in controls (P < 0.0001). Comparing the PKP3 levels in patients and controls, the area under the curve was 0.852 (95% confidence interval, 0.76-0.94; P < 0.0001) in receiver operating characteristic analysis. A higher blood level of PKP3 mRNA was associated with a more advanced stage (P = 0.025), pT(3-4) tumors (P = 0.028), metastasis (P = 0.021), and residual (R2) disease (P = 0.037). Higher PKP3 mRNA was associated with the risk of cancer progression and death (odds ratio, 3.875; 95% confidence interval, 1.781-8.430; P = 0.001). CONCLUSIONS: Increased PKP3 mRNA was detected in the blood of gastrointestinal cancer patients. Significant correlations were found with advanced stage, pT(3-4), metastatic disease, and the residual disease status. PKP3 mRNA in blood was associated with the risk of cancer progression and death. IMPACT: PKP3 mRNA can be used as a marker of subclinical disease in gastrointestinal cancer and thus holds potential clinical relevance as a predictor for disease outcome.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Gastrointestinales/sangre , Células Neoplásicas Circulantes/metabolismo , Placofilinas/genética , ARN Mensajero/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Humanos , Masculino , Persona de Mediana Edad , Células Neoplásicas Circulantes/patología , Placofilinas/sangre , Valor Predictivo de las Pruebas , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Detection of tumor cells in the blood, or minimal deposits in distant organs as bone marrow, could be important to identify cancer patients at high risk of relapse or disease progression. Quantitative polymerase chain reaction (PCR) amplification of tissue or tumor selective mRNA is the most powerful tool for the detection of this circulating or occult metastatic cells. Our study aims to identify novel gastrointestinal cancer-specific markers for circulating tumor cell detection. METHOD: Phase I preclinical study was performed by means of computational tools for expression analysis. In silico data were used to identify and prioritize molecular markers highly expressed in gastrointestinal cancers but absent in hematopoietic-derived libraries. Selected genes were evaluated by means of qRT-PCR in gastrointestinal cancer and hematopoietic cell-lines, normal human bone marrows and bloods, tumor tissue, and blood from cancer patients. RESULTS: Novel and known mRNA markers for circulating tumor cell detection in gastrointestinal cancer have been identified. Among all the genes assessed, PKP3, AGR2, S100A16, S100A6, LGALS4, and CLDN3 were selected and assays based on blood qRT-PCR were developed. Reliably qRT-PCR assays for the novel targets plakophilin 3 (PKP3) and anterior gradient-2 (AGR2) to identify blood-borne cells in cancer patients were developed. CONCLUSIONS: Novel and known gastrointestinal-specific mRNA markers for circulating tumor cells have been identified through in silico analysis and validated in clinical material. qRT-PCR assay targeted to PKP3 and AGR2 mRNAs might be helpful to detect circulating tumor cells in patients with gastrointestinal cancer.