This study examined both cachexia-inducing factors and patients with various cancers to better understand the disparity between cancer types and developing cachexia.
A biological dimension of tumor-secreted elements could potentially be helpful in identifying the disparity between cancer types and the likelihood of developing cachexia, according to a recent study published inJournal of Cachexia, Sarcopenia and Muscle.1
Even more, the study revealed that cachexia-inducing factors (CIFs) have a tumor-specific profile that could help improve targeted therapies for cancers that develop high levels of cachexia.
“Our results revealed tumor-specific secretome transcriptional patterns, potential mediators, and pathways associated with the syndrome,” wrote the researchers. “We also showed that a set of 25 CIFs presented a tumor-specific expression profile, which was significantly associated with poor prognosis and correlated with the prevalence of cachexia and weight loss in cancer patients.”
The results from expression profiling of secreted genes in different cancer types highlighted pathways and mediators within the tumor environment that could potentially play a role in cachexia. The CIFs presented a tumor-specific expression profile where they found a correlation between the number of upregulated genes, cachexia prevalence (r2, 0.80; P = 0.002) and weight loss (r2, 0.81; P= 0.002).
The study obtained gene expression profiles from 4743 tumors across 12 different cancer types and compared them to 2737 samples of normal tissues from the same organs. The highest prevalence of cachexia was found in pancreatic, esophageal, gastric, lung, and liver cancers, while breast and prostate cancers did not associate with higher levels.
“Cachexia-inducing factors, mainly deriving from cancer, had already been associated with development of the syndrome but it was not yet possible to link them to this variation in its prevalence and severity,” primary researcher Robson Francisco Carvalho said in a press release. “In the case of cancer of the pancreas, for example, which correlates closely with cachexia, we found alterations in the expression of 14 out of 25 genes that encode cachexia-inducing factors. In prostate cancer, which does not, we found no change in the expression of any of these 25 genes.”2
The researchers pointed out that this study is the first in the field to indicate the potential influence of infiltrating immune cells in tumor types that are correlated with cachexia. While this study is part of the progress in better understanding cachexia, the researchers stress that further research is required on the source of these molecules to help advance understanding of cachexia to ultimately improve therapeutic strategies.
Estimates suggest about 80% of advanced-stage cancer patients will develop cachexia, a “multifactorial syndrome characterized by muscle wasting, leading to a significant weight loss that impacts patient’s quality of life, tolerance to treatment, response to therapy, and survival.” Patients with end-stage cachexia are typically expected to survive for no longer than 3 months.
One limitation of the study centered around the inability to validate diagnostics of cachexia because of the absence of clinical data in several of the patients from the 12 central tumor types from the study. Despite this limitation, the researchers utilized a systematic investigation to validate the expression of CIF genes in cancer cells using human samples and tumor types. This allowed for the identification of potential biomarkers and mediators of cachexia, ultimately providing insights into the study of cachexia.
“The synergic expression of the CIFs in several tumor types highlights the importance of this group of soluble factors in cancer pathophysiology and presents a strong case for their targeting in specific anti-cachexia therapeutic development in different tumor contexts,” wrote the researchers. “In addition, the tumor-specific profile of CIFs will facilitate the development of better targeted therapies for clinical decisions.”
1. Freire PP, Fernandez GJ, de Moraes D, et al. The expression landscape of cachexia-inducing factors in human cancers. Journal of Cachexia, Sarcopenia and Muscle. DOI: 10.1002/jcsm.12565.
2. Study can help identify cancer patients most likely to develop cachexia [news release]. Published March 4, 2020. http://agencia.fapesp.br/study-can-help-identify-cancer-patients-most-likely-to-develop-cachexia/32658/. Accessed March 5, 2020.