Prognostic relevance of hTERT mRNA expression in ductal adenocarcinoma of the pancreas

Abstract

Telomerase is thought to play an essential role in tumorigenesis and progression. Its activity is directly correlated with the expression of its catalytic subunit, human telomerase reverse transcriptase (hTERT). A correlation of transcript expression with a poor prognosis has been detected in different human malignancies. However, data on hTERT in pancreatic ductal adenocarcinoma (PDAC) are purely descriptive so far. Therefore, we evaluated the impact of hTERT expression on patients' prognosis. Human telomerase reverse transcriptase mRNA isolates from 56 human microdissected PDAC tissues were analyzed by quantitative reverse transcription-polymerase chain reaction and multivariate Cox regression hazard test. Elevated hTERT transcript levels were measured in 23 of 56 PDAC tissues, 33 patients showed no detectable transcripts. Unexpectedly, a low expression of hTERT mRNA levels was associated with a worse prognosis for overall survival (relative risk = 5.33; P = .013) when compared to high levels, whereas undetectable expression showed an intermediate risk of tumor-related death. These data challenge previous findings outlining hTERT's negative impact on overall survival. The risk pattern obtained in PDAC suggests a more complex regulation of hTERT.

Figure 1

Prognostic relevance of hTERT mRNA expression, analyzed with multivariate Cox proportional hazard regression model for overall survival for 56 PDAC patients (UICC stages I–IV, R0–2 resection), adjusted for tumor stage, type of tumor resection, and patients' age. Cutoffs for expression of hTERT were the mean value (61 ag) and undetectable mRNA levels (0.00 ag): >61 ag (high); >0.00 to ≤61 ag (low), and 0.00 ag mRNA (not detectable) standardized to HPRT transcript levels.