Joint quantitative measurement of hTERT mRNA in both peripheral blood and circulating tumor cells of patients with nasopharyngeal carcinoma and its clinical significance

Abstract

BackgroundThe study was aimed to quantitatively detect mRNA levels of the catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore its significance in early diagnosis and treatment of NPC.MethodshTERT mRNA levels in peripheral blood and CTCs of 33 NPC patients before and after treatment with intensity-modulated radiation therapy (IMRT) or/and chemotherapy and 24 healthy controls were measured using real-time quantitative PCR (qPCR) and their correlations to clinic pathological factors of NPC were analyzed.ResultsPeripheral hTERT mRNA content was 10.75 ± 4.29 in NPC patients and 0.95 ± 0.37 in control subjects (P < 0.05), and had a significant correlation with patients’ clinical stage, T stage, and N stage (P < 0.05). Treatment of NPC patients at stages I and II with simple IMRT significantly reduced hTERT mRNA level from 5.60 ± 2.33 to 3.43 ± 1.42 (P < 0.05) and treatment of patients at advanced stage (III and IV) with induction chemotherapy followed by IMRT significantly reduced hTERT mRNA levels from 12.68 ± 3.08 to 10.68 ± 2.48 to 3.13 ± 1.69 (P < 0.05), respectively. In addition, the study also showed that hTERT mRNA content in CTCs of NPC patients was 10.65 ± 4.28, evidently higher than that of 1.09 ± 0.40 in control subjects (P < 0.05) and hTERT mRNA level in CTCs of NPC patients was obviously correlated to patients’ clinical stage, T stage and N stage (P < 0.05). After treatment, hTERT mRNA level in CTCs of NPC patients lowered from 10.65 ± 4.28 to 5.59 ± 2.32 (P < 0.05). The correlation analysis found that hTERT mRNA level in peripheral blood and CTCs of NPC patients were highly correlated with a correlation coefficient of 0.981.ConclusionshTERT mRNA levels in peripheral blood and CTCs of NPC patients were significantly enhanced compared to that in healthy controls and highly correlated. Changes in hTERT mRNA level was closely correlated to patients’ clinical stage and T stage. Radiochemotherapy could effectively reduce hTERT mRNA level in peripheral blood and CTCs. Thus, it is possible using the joint detection of hTERT mRNA level in peripheral blood and CTCs as a new biomarker for early diagnosis, treatment efficacy and prognosis of NPC.

Profiling the circulating mRNA transcriptome in human liver disease

“…www.oncotarget.com demonstrated in breast cancer [17,37]. Albumin mRNA has also been detected in the peripheral blood of advanced stage (TNM stages III and IV) HCC patients.…”

“…Several laboratories have demonstrated the existence of circulating mRNA in healthy subjects and those with a disease diagnosis [3][4][5][6][7][8][9][10][11][12][13]. For example, circulating hTERT mRNA levels have been reported to correlate with a diagnosis of hepatocellular carcinoma (HCC) [14,15] and with tumor progression [12,16,17]. Albumin (ALB) mRNA has also been detected in the circulation of advanced stage HCC patients and was reported to predict recurrence of HCC after transplantation [18,19].…”

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Liquid biopsy as a perioperative biomarker of digestive tract cancers: review of the literature

“…Further research is required to understand its clinical applications, including quantitative properties [75]. Although RNA is generally unstable in the blood, miR is a stable noncoding molecule consisting of 18-25 nucleotides [16][17][18][19]. This form of endogenous, single-stranded RNA has been implicated in a range of pathological processes, including cancer initiation and progression, and the remarkable stability makes it a useful biomarker for cancer diagnosis [16][17][18][19].…”

“…Recent studies have shown that in addition to DNA, cfNAs such as messenger RNA (mRNA), microRNA (miR), long noncoding RNA (lncRNA), and circular RNA (cir-cRNA) can be detected in the blood and are thus candidate blood-based biomarkers [16][17][18][19]. Other studies have suggested that some of these cfNAs present in the circulating blood are encapsulated in microvesicles such as exosomes, which ensures their stability.…”