Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa‐miR‐2053 and lncRNA‐RP1‐86D1.3 axis expression in malignant pleural mesothelioma

Abstract

Aim and Background: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM. Methods: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A (ARSA) gene expression with their epigenetic regulators microRNA (miR-2053) and long noncoding RNA (lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed.Results: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM. Conclusion: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies

“…In this study, the in silico analysis of the lncRNA expression using pleural mesothelioma and normal human pleura revealed 40 altered lncRNAs. Notably, RP1-86D1.3 [7] was not identified as differently expressed lncRNA. Additionally, Wright et al detected 33 lncRNAs differentially expressed in mesothelioma cell lines compared to MeT-5A [23], but only NEAT1 was identified in both studies.…”

“…Additionally, it is known that earlier detection of cancer can improve survival, at least for some cancer types [44]. Thus, for early diagnosis it will also be necessary to validate GAS5 as well as the previously identified RP1-86D1.3 [7] in a prospective study regarding their potential to detect mesothelioma in prediagnostic plasma samples and to complement calretinin and mesothelin. This validation procedure is an obligatory step to select appropriate candidate markers for early detection.…”

“…Particularly, long non-coding RNAs (lncRNAs) represent a versatile and promising group of potential markers, playing a role as oncogenes as well as tumor suppressors, and showing an altered expression in cancer [5,6]. However, to the best of our knowledge, RP1-86D1.3 is the only known circulating lncRNA for the detection of malignant mesothelioma so far, marked by a sensitivity of 83% and a specificity of 95% [7].…”

Development and validation of autophagy‐related‐gene biomarker and nomogram for predicting the survival of cutaneous melanoma

“…DRAM1 (DNA damage regulated autophagy modulator 1) is an encoded lysosomal membrane protein that induces autophagy by regulation of p62. The mRNA expression of DRAM1 was positive in malignant pleural mesothelioma patient and may play an important role in tumorigenesis and progression . Furthermore, RAB24 is an atypical RAB protein which is necessary for basal autophagy.…”

Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation

“…Taking into account the limitations mentioned above, many authors (74,83,85,94,102) suggested to explore together markers of different origin to overcome the poor sensitivity and specificity of single markers. These studies combine proteins (e.g., mesothelin, fibulin, and osteopontin concentration) and different epigenetic biomarkers, including DNA methylation, expression of miRNA, and also expression of long-noncoding RNAs (lncRNAs), which are non-coding RNAs mostly involved in transcriptional regulation (103).…”