In this study, we performed a comprehensive analysis of the largest ACB cohort and investigated the relationship between clinicopathological characteristics and patient survival. We also compared the differences in patient characteristics and prognostic factors between ACBC and EACB patients. We found that the age and tumor size were larger in ACB patients than in EACB patients, and the incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction were also higher in ACB patients. High expression of Vim was also seen more frequently in ACB patients. In both the ACB and EACB cohorts, the type of resection was associated with LRFS, and the type of resection and surrounding tissue invasion were associated with OS, but most other factors showed inconsistent survival between the two groups.
The above findings suggest that ACB may have different molecular biological features and clinical behaviors than EACB. These data help us to gain a comprehensive understanding of the prognostic factors of ACB so that reasonable prognostic risk stratification can be performed and patient survival can be improved.
Differences in Immunohistopathological and Clinicopathological Characteristics Between ACB and EACB
This study compared the differences in patient characteristics and prognostic patterns between ACB and EACB. We found similarities in the expression of most parameters between ACB and EACB, but the expression of Vim was higher in ACB. Overexpression of Vim, a major intermediate filament (IF) protein in mesenchymal cells, is closely associated with accelerated growth and infiltration and is a poor prognostic factor in many cancers18–21. Therefore, we hypothesized that ACB may be biologically more aggressive and have a higher recurrence rate than EACB. Similar to this hypothesis, it has been reported that spinal CB is more aggressive and more prone to recurrence than extremity bone CB9–11; in addition, our study also found that the size of tumors and the incidence of surrounding tissue invasion were greater in ACB patients than in EACB patients, and a larger tumor size and higher surrounding tissue invasion rate indicated high tumor aggressiveness and poor prognosis22, 23. In addition, ACB patients are also more likely to develop sensory or motor dysfunction, which is not difficult to understand. For anatomical reasons, the tumors in ACB patients tend to occur in the spine and skull, with tumors close to the neurovasculature, which also makes the risk of nerve damage considerably higher than that in EACB patients.
Furthermore, we found that the average age of ACB patients is greater than that of EACB patients, and interestingly, it has been reported in the literature that the majority of CB patients are under 50 years of age, mainly affecting people aged 20-30 years5, 24, while the age of predilection for cranial CB patients is 40 years7. Regarding the site of occurrence, the most common site in young CB patients is the end of the long bones4, while in older patients, the preferred location of the tumor is more variable and may involve multiple sites, such as the craniofacial skeleton24, 25. This could also explain the fact that the mean age of ACB patients is greater than that of EACB patients. However, further large sample data comparisons are needed for subsequent research analysis.
Influence of the type of resection and surrounding tissue invasion on the survival of ACB and EACB
Due to the aggressive nature of CB, surgical treatment appears necessary5, 10, 26, and our study found that performing wide tumor resection resulted in good LRFS in patients, which is consistent with this finding. Most scholars recommend removing as much complete tumor tissue as possible to reduce postoperative recurrence rates and achieve good disease control5, 10, 26. A recent study on CB of the spine also further confirmed the results of this study27. In addition, it has been reported that patients will have a high probability of tumor recurrence if residual lesions remain after surgery7.
At the same time, our analysis found that patients with surrounding tissue invasion had shorter OS, which is not difficult to understand and is consistent with previously reported findings that if the tumor infiltration is extensive or the tumor itself is adjacent to important nerves, blood vessels, and other tissue structures, it is difficult to obtain wide resection of the tumor during surgery, thus making postoperative recurrence more likely in patients7, 27. In addition, whether it is due to the long-term infiltration and destruction of the body by tumor tissues or damage to important neurovascular or tissue organs during surgery, patients who have the further aggravation of symptoms are likely to cause a decrease in their antitumor immune function, which also creates conditions for tumor recurrence and leads to an increased recurrence rate28–30.
Influence of chicken-wire calcification on the survival of ACB patients
Chicken-wire calcification is widely present in the eosinophilic mechanism of CB and may serve as a diagnostic tissue feature of CB5, 31, 32. The present study is consistent with the results of a previous study from our integrative analysis, in which spinal CB patients with chicken-wire calcification expression have a better prognosis17. It has been shown that patients with calcification in the tumor tissue had significantly longer median progression-free survival and overall survival than patients without calcification33. Calcification is mainly the deposition of calcium salts and minerals, and bone bridging proteins are involved in the regulation of the calcification process34, while osteopontin can promote malignant tumor invasion, growth and metastasis35. Therefore, we speculate that the downregulation of osteopontin expression in tumors of ACB patients reduces their aggressiveness. In addition, it has even been found that even if different types of calcification exist in the tumor tissue of CB patients, the prognosis of patients with chicken-wire calcification is better than that of patients with nonchicken-wire calcification36, which may be related to the different biological behaviors arising from the different spatial arrangements, and all these theories deserve further investigation.
Influence of Adjuvant Radiotherapy on the Survival of EACB
Another major finding showed that patients with EACB treated with adjuvant radiotherapy had a worse prognosis, which is similar to previous reports that radiotherapy may lead to the transformation of CB into a more malignant sarcoma2, 7, 27, and it has even been reported that any modality of adjuvant therapy is prohibited for CB37. In contrast, radiotherapy has been reported to reduce the tumor recurrence rate in patients and can be used in patients with postoperative recurrence and inoperable treatment, resulting in a good prognosis9. Therefore, the prognostic role of radiotherapy in CB remains controversial, and future studies with larger sample sizes and detailed information on patient radiotherapy combined with in vivo and in vitro experiments are needed to further evaluate the effects of adjuvant radiotherapy in patients with CB. Current studies suggest that radiation promotes epithelial mesenchymal transformation and induces the production of new cancer stem cells from nonstem cells in various human cancers38, 39. This idea may be the theoretical basis for the poor prognosis of CB patients receiving adjuvant radiotherapy, so the detection of newly generated cancer stem cells and their proteomic study may help to identify the precise mechanisms of progression in these CB patients.