Malignant peritoneal mesothelioma cancer has shown to be an aggressive and incurable form of tumor having a median survival of 12 months. Its intrinsic chemo- and radio-resistance has resulted in treatment nihilism for over 40 years. However, there have been rare cases that have demonstrated good responders and long-term survivors. Mesothelioma can occur in the cells lining the pleura, peritoneum, or tunica vaginalis, and around 70% of cases involve the pleural location. The most common is the epithelial subtype, which is an essential prognostic factor in comparison to the mixed and sarcomatous subtypes. Parietal pleura is the most common site of mesothelioma occurrence. Here, the tumor develops in a loco-regional pattern, usually spreading to the visceral pleura and invading the neighboring organs and body parts. Asbestos has been identified as the main carcinogenic factor, but mesothelioma can be induced through radiation and the Simian virus 40 (SV40) has also been held responsible, but mostly as a co-factor. Fine asbestos fibers have been found both in the parietal and visceral pleura and also in the lung. Since it is still not known why mesothelioma mostly occurs in the parietal pleura and not in the visceral pleura, it can be assumed that the parietal pleura is more susceptible to oncogenic factors in comparison to the visceral pleura.
In addition, cytogenetic studies have revealed that mesotheliomas are characterized by variable and highly complex chromosomal mutations, and only a few important common features have been found, for instance the deletion of the 9p21 which includes the CDKN2A gene. Therefore, genome-wide microarray analysis can be a more effective way of identifying the most essential common and critical genes and pathways that are involved in its biology. Genome-wide studies that focus on comparing pleural mesothelioma and non-cancerous types of parietal and visceral pleura are yet to be published. The primary objective of this specific study was to compare and analyze the gene profile of human mesothelioma and normal parietal and visceral tissues, with special focus on differential gene expression and pathway analysis correlated to gene function.
Genome-wide analysis of malignant peritoneal mesothelioma in comparison to normal parietal pleura revealed many new and remarkable expression patterns that were highly relevant as far as the biology of mesothelioma is concerned. Differences in gene expressions noticed between the parietal and visceral pleural tissues, as explained here for the first time, are very important and can be very useful in understanding the parietal pleura’s susceptibility to the development of mesothelioma. Several of those features have been identified mostly in epithelial malignant tumors, thereby demonstrating essential genotypic similarities between this type of tumor (that possibly has a mesodermal origin) and epithelial cancer. In addition, 150 differentially expressed genes were identified that did not have any known function. This may turn out to be an important finding in the future.
When examining gene expression data, one must always remember that they
only reflect relative values. So, for instance overexpression in tumor
can also be indicative of down-regulation in the healthy tissue.