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. 2021 Oct 14;11:692788. doi: 10.3389/fonc.2021.692788

Table 10.

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.