Clinical value of long non-coding RNA HOXA terminal transcript antisense RNA in the diagnosis of pancreatic cancer / 中华胰腺病杂志

ABSTRACT

Objective:To investigate the clinical value of the long non-coding RNA HOXA terminal transcript antisense RNA (HOTTIP) for diagnosing pancreatic cancer (PC).Methods:PC tissue and adjacent normal tissue (>1 cm distant from cancer tissue) from 18 PC patients confirmed by pathology after surgery were collected from June 2017 to December 2018 in Xuzhou Central Hospital. Plasma samples from 78 PC patients clinically confirmed were collected, those from 78 healthy individuals were designed as healthy controls and those from 50 patients of liver cancer, 50 patients of colorectal cancer and 50 patients of gastric cancer were also collected as disease controls. HOTTIP expression in PC tissue and plasma of PC patients, disease controls and healthy controls was tested by real time quantitative polymerase chain reaction; the plasma CA19-9 level was tested by CLIA. The correlation between plasma HOTTIP, cancer tissue HOTTIP and plasma CA19-9 were analyzed, and the relationship between plasma HOTTIP and clinicopathological features was analyzed. The survival curves of patients with high and low expression of HOTTIP were drawn, and the difference of survival rates between the two groups was compared by log-rank test. Receiver operating characteristic (ROC) curves were drawn to calculate area under the ROC curve (AUC), and the diagnostic performance of plasma HOTTIP for PC was evaluated.Results:Compared to normal pancreatic tissue, the level of HOTTIP expression was significantly up-regulated in pancreatic cancer tissue (2.24±0.25 vs 0.62±0.11, P<0.001), the relative expression of plasma HOTTIP of PC, liver cancer, colorectal cancer, gastric cancer patients and healthy controls were 1.33±0.32, 0.57±0.17, 0.51±0.10, 0.41±0.09 and 0.54±0.05; HOTTIP level of PC patients was higher than that of liver cancer, colorectal cancer, gastric cancer patients and healthy controls (all P<0.05), but the difference on HOTTIP level between liver cancer, colorectal cancer, gastric cancer patients and healthy controls was not statistically significant. The plasma HOTTIP of PC patients had a strong positive correlation with plasma CA19-9 and also had a positive correlation with HOTTIP level in cancer tissue (all P<0.05); meanwhile the plasma level of HOTTIP was significantly correlated with TNM stage ( P=0.029), but not with sex, age, lymph node metastasis and tumor size. The median survival time of patients with high HOTTIP level was obviously lower than that of those with low HOTTIP level (15.9 months vs 30.6 months, P<0.05). The AUC of plasma HOTTIP for diagnosing PC was 0.81(95% CI 0.74-0.87). At the optimal cutoff value of 1.14, the diagnostic sensitivity, specificity and accuracy were 62%, 94% and 74%. By combining plasma HOTTIP with CA19-9, the diagnostic sensitivity, specificity and accuracy can be increased to 81%, 97% and 84%, respectively. Conclusions:Plasma HOTTIP level has a significant value in the diagnosis of PC.