br Conclusion Plasma PCGEM may be a potential
Conclusion: Plasma PCGEM1 may be a potential novel circulating biomarker for GC diagnosis and prognosis.
Abbreviations: GC, gastric cancer; PCGEM1, prostate cancer gene Compound C marker 1 ; qRT-PCR, reverse transcription-polymerase chain reaction
Key words: Gastric cancer, long non-coding RNA, PCGEM1, Diagnosis
Gastric cancer (GC) is one of the most common malignancies of the digestive system; GC is the fourth most common cancer type and the second leading cause of cancer-related deaths in China . Thus, developing strategies for the early diagnosis, and control of the invasion and metastasis of GC is an important research focus, which requires the identification of biomarkers and their underlying molecular mechanisms
. Currently, the gold standard of GC diagnosis is gastroscopy along with a pathology examination, which are invasive and uncomfortable procedures . Although humoral biopsy is relatively non-invasive, the traditional serum tumor biomarkers used for GC diagnosis have low sensitivity and specificity . With the development of high-throughput sequencing technology, the levels of circulating RNAs in the serum or plasma have been identified as new non-invasive diagnostic biomarkers for several cancer types .
Long non-coding RNA (lncRNA) is a class of non-coding RNAs that are longer than 200 nucleotides with limited protein-coding capacity . LncRNAs can regulate biological processes at multiple levels such as transcriptional, post-transcriptional, and epigenetic regulation . Accumulating evidence has confirmed that lncRNAs play important biological roles in the malignant phenotype of GC [8, 9]. In our previous study, we demonstrated that the hypoxia-responsive lncRNA prostate cancer gene expression marker 1 (PCGEM1) may play a role in the invasion and metastasis of GC through mediating the epithelial–mesenchymal transition . Under a hypoxic condition, the tumor-derived lncRNAs reshape their surrounding harsh microenvironment, and can also enter the bloodstream to reflect pathological and physiological changes [11, 12]. Moreover, other lncRNAs have been shown to be stable in plasma, which is a key requirement of a clinical biomarker [13, 14]. Given this background, we hypothesized that GC cells can release the lncRNA PCGEM1 to be detectable in plasma, which would offer a non-invasive method for GC detection and prognosis prediction.
To test this hypothesis, in the present study, we investigated the potential of the circulating level of the lncRNA PCGEM1 as a GC biomarker in plasma. First, we examined the expression of PCGEM1 in GC cells and para-cancer tissues, and in the plasma samples of GC patients and healthy controls. We then evaluated the correlation between PCGEM1 levels and clinicopathological characteristics, and analyzed the diagnostic efficiency of circulating PCGEM1 in patients with GC.
Materials and Methods
The study was approved by the Ethics Committee of Liaoning Cancer Hospital
& Institute. Informed consent was obtained from all subjects before they participated in the study.
Patients and samples
Between October 2015 and December 2018, 317 GC patients were enrolled in this study. All patients were diagnosed with GC by two pathologists after undergoing D2 lymph node-dissected gastrectomy. Patients treated with chemotherapy or radiotherapy before blood collection were excluded from the study. Tumors were staged according to the 8th edition of the TNM staging manual of the American Joint Committee on Cancer. In addition, 100 healthy individuals matched for sex and age with the patients were included as the control group.
All blood samples were collected in vacuum blood tubes with ethylenediaminetetraacetic acid anticoagulant before and after surgery and were processed within 1 h after collection. The blood samples were subjected to centrifugation at 5000 rpm for 10 min at 4°C, and the plasma was stored at −80°C until analysis.