When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).
“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.
They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.
The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.
The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.
Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.
The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”
Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.
“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.
The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.