Circulating Tumor Biomarkers Correlate With ¹³¹I Uptake And Prognosis In Differentiated Thyroid Cancer

Part 1 : Circulating Long Non-coding RNAs Act as Biomarkers for Predicting 131 I Uptake and Mortality in Papillary Thyroid Cancer Patients with Lung Metastases PurposeRecent evidence has shown that some plasma Lnc RNAs play important roles in differentiating between benign and malignant tumors,predicting the metastasis or recurrence of malignant tumors,and evaluating the therapeutic effect and prognosis of malignant tumors and so on.To the best of our knowledge,circulating lnc RNAs haven't been analyzed and compared between non-¹³¹I-avid and ¹³¹I-avid lung metastases from PTC.The aim of the current study were to explore plasma Lnc RNAs as a novel biomarker panel for the diagnosis of non-¹³¹I-avid lung metastases of PTC and to investigate the plasma Lnc RNA expression levels associated with survival in PTC patients with lung metastases.Methods204 PTC patients with lung metastases who had been pathologically diagnosed after total thyroidectomy with neck lymph node dissection between 2005 and 2015 were enrolled in the study.The patients were divided into groups: a non-¹³¹I-avid groups and ¹³¹I-avid groups.The expression of Lnc RNAs was examined using an Lnc RNA microarray chip.The Lnc RNAs with the most significant difference in expression between PTC patients with non-¹³¹I-avid lung metastases and PTC patients with ¹³¹I-avid lung metastases were verified by quantitative reverse-transcription polymerase chain reaction?q RT-PCR?.The Kaplan–Meier method was used to determine whether the plasma Lnc RNA levels might be indicative of patient prognosis.ResultsCompared with ¹³¹I-avid lung metastases,we found that there were 1006 lnc RNAs that were upregulated?fold change ?2.0 and P<0.05?and 705 that were downregulated?fold change ?2.0 and P<0.05?in non-¹³¹I-avid lung metastases.q RTPCR confirmed that two Lnc RNAs?ENST00000462717 and ENST00000415582?were upregulated and two?TCONS₀0024700 and NR₀28494?were downregulated in the non-¹³¹I-avid lung metastases of PTC.Receiver operating characteristic curve?ROC?analyses indicated that the use of these four Lnc RNAs had high diagnostic sensitivity and specificity for predicting non-¹³¹I-avid lung metastases of PTC.The merged areas under the curve for ENST00000462717,ENST00000415582,TCONS₀0024700 and NR₀28494 in the training and validation sets were 0.890,0.936,0.975 and 0.918,respectively.Low plasma Lnc RNA levels?ENST00000462717 and ENST00000415582?and high plasma Lnc RNA levels?TCONS₀0024700and NR₀28494?were also found to be associated with better prognosis of PTC patients with lung metastases?P<0.001?.Conclusions ENST00000462717,ENST00000415582,TCONS₀0024700 and NR₀28494 may be used as novel and minimally invasive markers for the diagnosis and prognostic assessment of non-¹³¹I-avid lung metastases from PTC.Long-term followup of the patients in the current study and a prospective study with a larger sample size are needed to further validate the usefulness of circulating lnc RNAs in the diagnosis and prognostic assessment of non-¹³¹I-avid lung metastatic diseases from PTC.Part 2:Circulating Tumor Cells Predict Distant Metastases,Refractory to Radioiodine and Prognosis in Differentiated Thyroid Cancer PurposeAs biomarkers,circulating tumor cells?CTCs?from solid tumors can predict metastases and prognoses,and help monitor treatment efficacy.However,conventional Cell Search methods have low sensitivity to differentiated thyroid cancer?DTC?CTCs.In this study,for the first time,we used negative enriching?NE?immunofluorescence–in situ hybridization?i FISH?of chromosome 8 to capture and identify CTCs in DTC patients;and investigated how CTCs correlate with clinicopathological factors and prognoses in DTC patients with distant metastases?DM?.MethodsIn this study,we enrolled 72 patients with DTC before they underwent 131 I treatment,and 30 healthy controls?HC?.Their CTCs were measured in 7.5 ml peripheral blood using the NE–i FISH technique.ResultsWe detected CTCs in 62?86.11%?of the 72 subjects with DTC.The mean number of CTCs in patients with DTC with DM?DM+?was significantly higher than in the HC group?P=0.0016?and DTC patients without DM?DM-;P<0.001?.We found ? 5 CTCs were significantly associated with DM+ DTC?P=0.009;sensitivity:64.3%;specificity: 84.8%?;? 7 CTCs were related to response to 131 I treatment?sensitivity: 73.7 %;specificity: 69.6 %?,and were also associated with worseprognosis in DM+ DTC?P<0.001?.ConclusionsWe found ? 5 CTCs to be a potential predictive index for DM+ DTC;and ?7CTCs as a possible indicator of response to 131 I treatment and prognosis in DM+DTC.