According to the new Chinese research, soluble mesothelin-related peptide- SMRP is the best biomarker for the diagnosis of malignant mesothelioma in comparison with other biomarkers, regardless of its low sensitivity.
Even though the sensitivity is low, but according to Chinese research, the diagnostic significance of the SMRP biomarker is excellent in comparison with the other biomarkers for the detection of malignant pleural mesothelioma.
Soluble mesothelin-related peptide- SMRP is resulting in pieces of the breakdown of the mesothelin protein, and is used to diagnose malignant mesothelioma. The specificity of this method to indicate the absence of mesothelioma is very high, but the sensitivity that detects the presence of cancerous cells in pleura is not up to the mark. Still, the Chinese researchers believe that it can provide trustworthy evidence to examine the condition of malignancy of cancerous cells further.
SMRP's are the small pieces of protein mesothelin found in the lining membranes of the cavities around the lungs, abdomen, and heart. Mesothelial cells express this protein but a significant rise in the level of mesothelin calls for some trouble.
Doctors find this mesothelin protein in high levels in various cancers such as sarcomas, pancreatic carcinoma, some gastrointestinal carcinoma pulmonary carcinoma, ovarian cancer, and malignant mesothelioma.
Production of SMRP occurs after the breakdown of this protein in the pleural cavity. And by detecting the presence of these peptides and measuring their quantity, the presence of mesothelioma cancer is diagnosed.
The use of mesothelin as a biomarker for the diagnosis of mesothelioma is an FDA approved method.
SMRP has been extensively studied to be an excellent tumor marker for the diagnosis of mesothelioma. Mainly the presence of SMRP is checked in the blood test. And in the past few years, several other biomarkers have also been devised for the diagnosis of malignant mesothelioma.
In the meta-analysis done by the Chinese researchers, the valuable importance of SMRP's in the pleural effusion has been studied.
Here, the researchers have revealed that though this method produces false-positive results sometimes, but "..high specificity of SMRPs could point out mesothelioma, which provides strong evidence for further invasive examination."
Different Biomarkers for the Diagnosis of Mesothelioma
For the diagnosis of malignant mesothelioma in the body, various biomarkers including, fibulin-3 (FBLN3), osteopontin, c-MET expression, ki-67 ratio, neutrophil to lymphocyte ratio, and SMRP, are used.
Among these three blood-based biomarkers, SMRPs, fibulin-3 (FBLN3), and osteopontin are the most extensively investigated and accessible diagnostic biomarkers used to date for the detection of malignant mesothelioma.
Fibulin-3 and Osteopontin are other proteins used as the diagnostic tumor markers of malignant pleural mesothelioma. In recent studies, analyzing a more than 350 malignant pleural mesothelioma patients, the results have shown a lack of diagnostic significance of fibulin-3 and Osteopontin.
Currently, SMRP is the only blood-based biomarker that is approved and validated by the FDA used for mesothelioma. The blood test for this is clinically called MESOMARK.
In addition to the blood, after the breakdown of mesothelin protein in the membrane, the resulting pieces/ SMRPs are also released in the lung fluid or pleural effusion (PE). Patients suffering from pleural mesothelioma have an excess amount of this lung fluid. And the detection of the amount of SMRP's in this fluid is correlated with the extent of malignancy of mesothelioma in the body.
As the researchers have written in the paper,
"SMRPs in PE can be a good indicator of the existence of MPM, high level of pleural SMRPs are highly suspicious for MPM..."
Research Pattern of the Meta-Analysis of Different Biomarkers
Researchers from the Capital Medical University prepared a systematic review of several scientific pieces of research done in the past to analyze the diagnostic significance of SMRP for malignant pleural mesothelioma. The primary target of this study was to investigate the value of SMRP in the pleural effusion on a larger scale within original research.
The Chinese researchers studied 13 studies in their research design based on SMRP in pleural effusion. Among a total of 3359 cases, 759 were of malignant pleural mesothelioma, 1061 of malignant pleural effusion and 1539 cases were of benign pleural effusion.
The researchers revealed that using SMRP in PE as a biomarker diagnosed the presence of mesothelioma in 69% of the cases correctly. In medical terms, it is called sensitivity in which the results show a positive rate of the disease.
And the researchers found that SMRP's in the PE are much better in ruling out the existence of mesothelioma. This research is called specificity, and for this test, it was about 90%.
As the researchers wrote in the paper,
"..high specificity revealed that PE-SMRPs above the cutoff value could be helpful for confirming MPM, so further invasive examination, will be strongly supported. On the other hand, low sensitivity limited SMRPs’ diagnostic performance."
Limitations of this Biomarker for Other Types of Mesothelioma
Doctors find the presence of SMRP in the pleural effusion of malignant mesothelioma patients, but the actual pathway or process of their release is still under investigation. The process could be because of the shedding of mesothelin protein after an enzymatic cleavage or other splicing events.
Secondly, the amount of SMRP's produced in different types of mesothelioma is different. For example, SMRP's are in high levels in cases of epithelial mesothelioma; and are in the least amount in Sarcomatoid mesothelioma. As the authors indicated in the paper,
"SMRPs is most expressed in epithelial mesothelioma, while almost absent in sarcomatous type. "
Moreover, the content of SMRP's in the pleural effusion is shallow in the initial stages of mesothelioma. Chinese researchers have related this fact with the sensitivity of this method, saying,
" SMRPs content is less in the early stages of mesothelioma, so more cases of early (I II period) are included, which will also lead to poor sensitivity."
These are the main reasons why doctors opt for different diagnostic tools for different types of mesothelioma. For the proper diagnosis of mesothelioma, doctors study the individualistic approach for every patient in which his histochemical testing and imaging of the tumor. And through systematic biomarkers and different diagnosis tools, confirmation of the mesothelioma, type of mesothelioma, and the extent of metastasis is detected.
As per the recent stats by the American Society of Clinical Oncology, about 3000 Americans go through mesothelioma diagnosis. Thus, more refined and accurate diagnosis tools can pave the way for the early start of the treatment.