Table 4.
Current studies on other markers.
| Marker | Reference | Sample location | Sample size (N) | Finding |
|---|---|---|---|---|
| CASR | Liu et al. (174) | Tumor tissue | 120 | CASR expression in lung cancer tissues was significantly higher than that measured in adjacent and normal lung tissues. The expression of CASR in lung cancer tissues with BM was higher than that observed in non-metastatic lung cancer tissues. |
| BSP | Bellahcene et al. (33) | Primary lung tumor tissue | 86 | BSP was not specifically detected in normal lung tissue with the exception of cartilage associated with bronchi. Most adenocarcinoma (74%) and all squamous carcinoma of the lung samples examined exhibited detectable levels of BSP. |
| Zhang et al. (70) | Primary lung tumor tissue | 180 | BSP protein expression in the primary resected NSCLC was strongly associated with BM and could be used to identify high-risk patients after primary tumor resection. | |
| He et al. (71) | Serum | 146 | The mean serum BSP levels in individuals with BM were significantly higher than those recorded in non-BM NSCLC and controls (p<0.001). The cut-off value was 33.56 ng/ml, and sensitivity and specificity values were 77.8% and 81.1%, respectively. | |
| BMP2 | Bieniasz et al. (168) | Tumor tissue | The expression levels of VEGF, BMP2, and BMP4 mRNA were significantly higher (7.1-fold, 25.6-fold, and 2.3-fold, respectively) in lung cancer samples than those in adjacent normal lung tissues. | |
| Choi et al. (169) | Serum | 150 | The NSCLC group demonstrated significantly higher levels of serum BMP2 than the control group. The median serum levels of BMP2 in the advanced stage group (stage IIIb or IV) were significantly elevated compared with those of the localized stage group (stages I, II, and IIIa). | |
| Fei et al. (170) | Serum | 84 | Serum BMP2 levels were significantly decreased in patients who achieved objective response after two cycles of chemotherapy. | |
| Huang et al. (171) | Tumor tissue | in vivo study | Activation of BMP2 signaling can enhance BM of Lewis lung carcinoma. | |
| CYFRA and CEA | Numata et al. (182) | Serum/tumor tissue | 131 | Elevated serum CEA and CYFRA levels appear to provide useful clinical information on the presence of BM and liver metastasis, as well as multiple-organ metastases, although they were not a powerful indicator of prognosis. |
| Tissue factor | Xia et al. (186) | Serum | 100 | Patients with high tissue factor expression levels tended to have worse overall survival performance, and downregulation of tissue factor inhibited the invasion and metastasis of NSCLC cells in vitro and in vivo. |
| Cell-free DNA (cfDNA) | Pecuchet et al. (192) | Serum | 124 | The presence of circulating tumor DNA at baseline was an independent marker of poor prognosis. |
| Ettinger et al. (83) | Serum | 282 | DNA median turnaround time was significantly shorter than that of tissue (9 vs. 15 days, respectively; p<0.0001) | |
| Ye et al. (193) | Tumor tissue | 186 | Patients with BM had higher concentrations of cfDNA and worse survival outcome. |
BM, bone metastasis; BMP2, bone morphogenetic protein 2; BSP, bone sialoprotein; CASR, calcium sensing receptor; CEA, carcinoembryonic antigen; CYFRA, cytokeratin 19 fragment; NSCLC, non-small-cell lung cancer; VEGF, vascular endothelial growth factor.