Bone Metastasis Of Lung Cancer Research Articles

Elevated N-telopeptide as a potential diagnostic marker for bone metastasis in lung cancer: A meta-analysis.

BackgroundGrowing evidence indicates that the cross-linked N-telopeptide of type I collagen (NTx) is likely to be involved in the development of bone metastasis among lung cancer patients. We perform a meta-analysis to disclose the correlation between bone metastasis and NTx and also to evaluate its value in diagnosis of bone metastasis (BM) in lung cancer.MethodElectronic databases were searched and calculated the weighted mean difference (WMD) with 95% confidence interval (CI) to assess the expression difference of NTx between BM+ and BM- lung cancer patients. Moreover, we conducted a sensitivity and specificity test and drew a summary receiver operating characteristic curve (SROC) to assess the diagnostic value of NTx in discerning bone metastasis.ResultsA total of eleven studies with 1108 individuals were included in this analysis. The results showed an increased NTx was correlated with the incidence of lung cancer (P < 0.001). The overall sensitivity and specificity of serum NTx (sNTx) for discerning bone metastasis was 0.74 (95% CI = 0.67 to 0.79) and 0.85 (95% CI = 0.80 to 0.89), respectively. As for urine NTx (uNTx) the pooled sensitivity and specificity was 0.77(95% CI = 0.67 to 0.86) and 0.81(95% CI = 0.76 to 0.86). The area under the SROC curve was 0.8889(SE = 0.0255) and 0.8655(SE = 0.0254) for sNTx and uNTx respectively.ConclusionsThe elevation of NTx in lung cancer was positively related with the development and progression of bone metastasis. A higher specificity over sensitivity of NTx suggested that it is a more accurate biomarker to distinguish patients without bone metastasis. Regarding SROC curve, sNTx may be a better choice.

Application of bone metabolism markers tP1NP, beta-CTx and BAP in bone metastasis of lung cancer

Objective To investigate the diagnosis, therapeutic monitoring and prognosis value of the total procollagen type 1 amino-terminal propeptide (tP1NP), beta-C-terminal telopeptide (β-CTx) and bone alkaline phosphatase (BAP) in the bone metastasis of lung cancer. Methods With the case-control study method, the serum levels of tP1NP, β-CTx and BAP in 196 lung cancer patients, including 109 patients with bone metastases, 87 patients without bone metastases, and 106 healthy controls at the Shanghai Sixth People′s East Hospital affiliated to Shanghai Jiao Tong University between 2014 and 2015 were quantitatively detected by chemiluminescent immunoassay. Receiver operating characteristic (ROC) curve was calculated to assess the diagnostic value. Survival curve was performed by Kaplan-Meier method. Results The concentration of tP1NP, β-CTx and BAP in the lung cancer patients with bone metastasis were significantly higher than that in the lung cancer patients without bone metastasis (Z=-5.642, P<0.001; Z=-3.783, P<0.01; Z=-8.923, P<0.01). ROC curve analysis showed that the AUC of tP1NP, β-CTx and BAP were 0.874, 0.776 and 0.678 respectively(P<0.05). The AUC of the combined three markers was 0.925(95% CI 0.867-0.963), with sensitivity of 77.11% and specificity of 98.11%. The levels of tP1NP and β-CTx were associated with the clinical response. The concentration of tP1NP, β-CTx were significantly decreased in patients achieved remission(t=4.607, P<0.05; t=5.355, P<0.05). Survival analysis showed that higher concentration of tP1NP was correlated with poor prognosis[OR=3.287, 95% CI (1.118-9.661), P<0.05]. Conclusions The levels of tP1NP, β-CTx and BAP cloud be used for the differential diagnosis of bone metastasis of lung cancer, and the combined usage was more effective. tP1NP and β-CTx cloud be used in therapeutic monitoring of lung cancer patients with bone metastasis. Moreover, tP1NP could be used as prognostic biomarker in lung cancer patients.(Chin J Lab Med, 2017, 40: 860-864) Key words: Lung neoplasms; Bone neoplasms; Neoplasm metastasis; Peptide fragments; Procollagen; Alkaline phosphatase

Prognostic score for life expectancy evaluation of lung cancer patients after bone metastasis

BackgroundThis study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis. MethodsA retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors. ResultsA total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3–4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17–1.73), and 1.30 (95% CI 1.06–1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively. ConclusionsPrognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer.

SY7-4 - Controversies and consensus on the management of bone metastases of lung cancer

SY7-4 - Controversies and consensus on the management of bone metastases of lung cancer

Les métastases osseuses des cancers broncho-pulmonaires

Bone metastases of lung cancer are a subject of interest due to significant incidence and skeletal related events affecting more than one in two patients. Bone metastases may be responsible for severe functional impairment and deep impact on the quality of life. The treatment relies on antalgic and systemic bone targeted therapy (zoledronic acid, denosumab). In addition, when bone metastases become symptomatic or complicated (fractures, spinal cord compression, severe pain) local specific treatments may be proposed. These treatments are constantly evolving (radiotherapy, interventional radiological techniques, surgery) and may be combined in some cases. Thus optimal management of complex bone metastases should be decided in multidisciplinary bone metastases staff to propose a personalized strategy, harmonized with the global oncological treatment.

The risk factors of bone metastases in patients with lung cancer

The risk factors of bone metastasis in patients with lung cancer are still unclear. Here, a retrospective study including a series of consecutive patients who were diagnosed with lung cancer between January 2005 and November 2016 was carried out. A total of 2021 patients with lung cancer were included in this study and 23.9% of them were found to be bone metastases. For patients with bone metastases, adenocarcinoma (62.1%) was the most common pathological subtype, and rib (62.3%) was the most frequent distant metastatic site, followed by thoracic (53.8%) and lumbar spine (40.4%). The histopathologic type, CA-125 level and the concentration of alkaline phosphatase (ALP) were identified as the independent risk factors for bone metastases in lung cancer (P = 0.002, P = 0.001 and P < 0.001). The sensitivities and specificities of diagnosing bone metastasis by CA-125 were 32.1% and 80.8%, and by ALP were 41.3% and 77.1%, respectively. Thus, the incidence of bone metastases in lung cancer patients was relative high, and physicians should pay attention to the histopathologic type, the serum CA-125 and ALP concentrations when patients were firstly diagnosed with lung cancer for early detecting bone metastases.

A meta-analysis survey of appropriate bone turnover markers in the detection of bone metastasis in lung cancer.

A number of studies have investigated the clinical significance of bone turnover markers (BTMs) for the diagnosis of bone metastasis (BM) in lung cancer; however, they led to contradictory results. The aim of this meta-analysis was to investigate whether BTMs differ between lung cancer patients with and without BM. Articles were identified by searching Medline, Embase, Web of Science and Scopus. The studies that were identified were pooled and the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) were calculated. Subgroup analyses and publication bias detection were also conducted. A final analysis of 1720 subjects (707 patients with BM and 1013 patients without BM) was performed from 16 cohort studies. From the pooled data in the meta-analysis, the total alkaline phosphatase (TALP) (104.35 U/l [95% CI 33.36-175.34]), bone-specific ALP (BALP) (13.24 μg/l [95% CI 8.50-17.98] or 6.84 U/l [95% CI 2.98-10.70]), C-terminal cross-linked telopeptide of type I collagen (ICTP) (5.07 μg/l [95% CI 3.58-6.56]) and N-terminal cross-linked telopeptide of type I collagen (NTX) (5.08nM bone collagen equivalent/l [95% CI 2.82-7.33]) were significantly lower among BM patients than non-BM patients. Subgroup analyses detected that the serum level of tartrate-resistant acid phosphatase isoform 5b was significantly reduced in Caucasian patients with BM (-0.64 U/l [95% CI -1.02 to -0.25]), while increased in Asian patients with BM (2.69 U/l [95% CI 0.08-5.31]), compared to patients without BM. The present meta-analysis suggested that serum measurement of TALP, BALP, ICTP and NTX might be helpful in detecting BM in lung cancer.

Neuron-specific enolase, histopathological types, and age as risk factors for bone metastases in lung cancer.

Lung cancer is a malignant tumor with high metastatic ability and bone is the most common site of distant metastasis of it. However, the independent risk factors for bone metastases of lung cancer remain largely to be elucidated. Here, we conducted a retrospective study to evaluate the correlation between clinical-pathological parameters, serum levels of neuron-specific enolase and CYFRA21-1, and bone metastases in lung cancer patients. The results revealed that patients with bone metastases were younger than those without metastases. Adenocarcinoma was the most frequent type of histopathology in patients with bone metastases. And the incidence of bone metastasis in patients with adenocarcinoma was significantly higher than those with other histopathological subtypes ( p < 0.001). Furthermore, the serum concentration of neuron-specific enolase was significantly higher in patients with bone lesions than those without bone metastases. Multivariate logistic regression analysis showed that patients' age (odds ratio = 1.024, p < 0.001), concentrations of neuron-specific enolase (odds ratio = 1.212, p = 0.004), and histopathological types (odds ratio = 0.995, p = 0.001) were the independent risk factors for bone metastases in patients with lung cancer. Thus, physicians should pay attention to these factors in order to identify bone metastasis earlier while patient was primarily diagnosed as having lung cancer.

Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways

Metastasis is the major cause of death from lung cancer. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells, but how it affects lung cancer cell invasion and metastasis is unclear. Herein, we found that quercetin inhibited the migration/invasion of non-small cell lung cancer (NSCLC) cell lines and bone metastasis in an orthotopic A549 xenograft model by suppressing the Snail-mediated epithelial-to-mesenchymal transition (EMT). Moreover, survival times of animals were also prolonged after quercetin treatment. Mechanistic investigations found that quercetin suppressed Snail-dependent Akt activation by upregulating maspin and Snail-independent a disintegrin and metalloproteinase (ADAM) 9 expression pathways to modulate the invasive ability of NSCLC cells. In clinical samples, we observed that patients with Snailhigh/p-Akthigh tumors had the shortest survival times. In addition, a lower survival rate was also found in ADAM9high patients than in ADAM9low patients. Overall, our results provide new insights into the role of quercetin-induced molecular regulation in suppressing NSCLC metastasis and suggest that quercetin has potential therapeutic applications for metastatic NSCLC.

A herpes simplex virus type 2-encoded microRNA promotes tumor cell metastasis by targeting suppressor of cytokine signaling 2 in lung cancer.

Certain viruses use microRNAs to regulate the expression of their own genes, host genes, or both. A number of microRNAs expressed by herpes simplex virus type 2 have been confirmed by previous studies. However, whether these microRNAs play a role in the metastasis of lung cancers and how these viral microRNAs precisely regulated the tumor biological process in lung cancer bone metastasis remain obscure. We recently identified the high expression of an acutely and latently expressed viral microRNA, Hsv2-miR-H9-5p, encoded by herpes simplex virus type 2 latency-associated transcript through microarray and quantitative polymerase chain reaction analyses which compared the expression of microRNAs in bone metastasis from lung cancer with primary lung cancers. We now reported that Hsv2-miR-H9-5p was highly expressed in bone metastasis and closely associated with pathological and metastatic processes of lung cancers. The functions of Hsv2-miR-H9-5p were determined by overexpression which results in an increase in survival, migration, and invasion of lung cancer cells in vitro. We determined that Hsv2-miR-H9-5p directly targeted SOCS2 mechanistically by dual-luciferase reporter assay. Then, we investigated the functions of SOCS2 in the progress of lung cancers. Reduction of SOCS2 dosage by hsv2-miR-H9-5p induced increased migration and invasion of lung cancer cells. Overexpression of SOCS2 inverted these phenotypes generated by hsv2-miR-H9-5p, indicating the potential roles of SOCS2 in Hsv2-miR-H9-5p-driven metastasis in lung cancers. The results highlighted that Hsv2-miR-H9-5p regulated and contributed to bone metastasis of lung cancers. We proposed that Hsv2-miR-H9-5p could be used as a potential target in lung cancer therapy.

Statins as Inhibitors of Lung Cancer Bone Metastasis

Statins as Inhibitors of Lung Cancer Bone Metastasis

151P - Predictors of survival in patients with bone metastasis of lung cancer

Background: In non-small cell lung cancer patients (NSCLC), median survival from the time patients develop bone metastasis is classically described being inferior to 6 months. We investigated the subcategory of patients having skeletal-related-event revealing NSCLC. The purpose of this study was to assess the impact of bone involvement on overall survival and to determine biological and tumoral prognosis factors on OS. Methods: We assessed the survival rates after bone metastasis and prognostic factors in 28 patients with bone metastases from lung cancer. We first assessed the survival rates and explored various prognostic factors of 28 patients with bone metastasis from lung cancer. We then preliminarily ascertained in a small group of patients whether treatment with an EGFR inhibitor had the potential to influence survival. Results: The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1–74.5 months). A favorable prognosis was more likely in women and patients with adenocarcinoma, solitary bone metastasis, no metastases to the appendicular bone, no pathologic fractures, performance status 1 or less, use of systemic chemotherapy, and use of an epithelial growth factor receptor inhibitor. Conclusions: Bone metastases are a common problem in advanced lung cancer. While the benefits of bone-targeted therapies have been demonstrated, their use is limited in non-trial populations. If better predictive markers of individual risk were available this might increase the appropriate use of bone-targeted agents. Legal entity responsible for the study: S. Jagadeesan Funding: N/A Disclosure: The author has declared no conflicts of interest.

High Serum HDGF Levels Are Predictive of Bone Metastasis and Unfavorable Prognosis in Non-Small Cell Lung Cancer.

Hepatoma-derived growth factor (HDGF) is a heparin-binding protein possessing mitogenic activity and could be secreted from necrotic cells passively or actively, thereby functioning as a damage-associated molecular pattern (DAMP). The high expression of HDGF in non-small cell lung cancer (NSCLC) tissues is associated with unfavorable prognosis. However, the clinical significance of serum HDGF has not been elucidated in NSCLC yet. In the present study, we compared the serum levels of HDGF in 235 patients with NSCLC (141 adenocarcinoma and 94 squamous cell carcinoma cases) with those in 40 healthy subjects. Moreover, we explored the correlation between serum HDGF levels and clinicopathologic factors or the overall survival rates. We thus found that the serum HDGF levels were significantly higher in NSCLC patients than those in healthy subjects (P < 0.001). Moreover, there was no significant difference in the serum HDGF levels between adenocarcinoma and squamous cell carcinoma. Importantly, the higher serum levels of HDGF were significantly associated with bone metastasis and with lower overall survival rates. Thus, serum HDGF was identified as an independent prognostic factor indicating poor prognosis of NSCLC. Using A549 human lung adenocarcinoma cell line, we demonstrated that an autophagy inhibitor, chloroquine, could inhibit the HDGF secretion, while quercetin, an autophagy inducer derived from a traditional Chinese drug, could facilitate HDGF secretion. In conclusion, high serum levels of HDGF were significantly correlated to bone metastasis and poorer prognosis of NSCLC. We suggest that anti-HDGF therapy is potential to protect NSCLC patients with advanced stages from bone metastasis.

Generation of a co-culture cell micropattern model to simulate lung cancer bone metastasis for anti-cancer drug evaluation

A549/OB co-culture micropattern was fabricated through μ-eraser strategy to mimic lung cancer bone metastasis for DOX efficacy evaluation.

Abstract 640: New models of breast and lung cancer bone metastases for preclinical efficacy testing

Abstract Introduction Clinically, bone is a very common site of metastatic spread in many cancers. In breast, and in particular cases of advanced estrogen receptor positive (ER+) cancers, the propensity of bone involvement is 85%. Similarly in lung cancer, 30-40% of patients with advanced disease develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available for the nonclinical evaluation of new treatment strategies. We present herein the development of four mouse models of breast and lung cancer suitable for screening of new therapies. Experimental procedures Human breast cancer cell lines BT-474 and MFM-223 and non-small cell lung cancer (NSCLC) cell lines NCI-H226luc and NCI-H322 were used. BT-474 is ER+, i.e. luminal B subtype and MFM-223 is basal subtype with androgen receptor (AR) expression. H226 originates from squamous cell carcinoma and H322 from adenocarcinoma of the lung. The different cell lines were inoculated in the tibia of female nude or NOD.scid mice. Half of the BT-474 inoculated mice had a s.c. slow release 17-beta estradiol pellet implanted. The formation of bone lesions was monitored by X-ray imaging. For H226 transfected with luciferase, tumor growth was also followed by bioluminescence imaging (BLI). Finally, tumor growth and type of bone lesion, i.e. ostelytic or oestoblastic, was confirmed by histology. Results Development of bone lesions was successful in 100% and 90% of animals, with or without hormonal supplementation respectively, four weeks after inoculation of BT-474 cells. Bone lesions were detected earlier in mice with estradiol pellet and were of lytic type. In contrast, bone lesions in mice without hormonal supplementation were strongly osteoblastic. For MFM-223, bone lesions were observed 4-6 weeks after inoculation and the success rate was 60% in nude mice and 70% in NOD.scid mice. For both lung cancer cell lines, 100% of the mice developed bone lesions and were detectable already two weeks after inoculation. H226luc cells developed osteoblastic-mixed lesions and H322 cells induced lytic lesions. Very interestingly, H226luc cells also formed lung metastases in all animals, as evidenced by BLI. Some lung metastases were also found in H322 inoculated mice. Conclusions Two new osteoblastic models are added to the current scarce selection and altogether four new bone lesion models representing different subtypes of breast and lung cancer were successfully established. The different types of bone reaction in these models offer a platform for studying the underlying pathways resulting in response to treatment in osteoblastic vs. osteolytic tumor microenvironment. Citation Format: Mari I. Suominen, Urs B. Hagemann, Yvonne Konkol, Jenni Bernoulli, Katja M. Fagerlund, Roger M. Bjerke, Jenny Karlsson, Jussi M. Halleen, Alan Cuthbertson. New models of breast and lung cancer bone metastases for preclinical efficacy testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 640.

The role of lncRNA MALAT1 in bone metastasis in patients with non-small cell lung cancer.

lncRNA metastasis-associated lung adencarcinoma transcript1 (MALAT1) plays an important role in the metastasis of lung cancer. Yet, its role in bone metastasis and the related mechanism remain unknown. The present study aimed to investigate the role of lncRNA MALAT1 in the bone metastasis of non-small cell lung cancer (NSCLC), including the expression pattern in tumor tissues, and the effect on the apoptosis, proliferation, migration and invasion of NSCLC cells. The expression level of MALAT1 in NSCLC tissues with/without bone metastasis and in NSCLC cell lines with (ACC-LC-319/bone2)/without (SPC‑A1) bone metastatic ability was determined with qRT-PCR and compared with t-test. si-MALAT1 was used to downregulate the expression of MALAT1 in ACC-LC-319/bone2 cells. The proliferation ability was assessed by MTT assay, and the apoptosis, migration, invasion and tumorigenesis invivo were also assessed to detect the effect of MALAT1 expression on NSCLC cells. In conclusion, the present study found that MALAT1 was significantly highly expressed in NSCLC tissues with bone metastasis and in NSCLC cell lines with high bone metastatic ability (P<0.0001). Downregulation of MALAT1 expression significantly inhibited proliferation and induced cell apoptosis in comparing with the negative controls. Our results also revealed that MALAT1 significantly increased the migration, invasion and tumorigenesis invivo, which suggests its important role in the bone metastasis of NSCLC.

Progress in the research on the mechanism of bone metastasis in lung cancer.

Lung cancer is still the predominant cause of cancer-associated mortality worldwide. The bone metastasis of lung cancer brings great suffering to the patient. Previous advances have provided insights into the mechanism of bone metastasis. Previous research has investigated lung cancer stem cells and three steps were determined for the lung cancer cells to metastasize to the bone: i) Escaping from the primary tumor; ii) moving in the circulation; iii) colonizing in the bone. Key molecules are involved in each of these process. Although there is a close association and similarity, dynamic microenvironments affect these processes. The receptor activator of nuclear factor-κB (RANK)/RANKL axis serves a vital role in the regulation of the generation and activation of osteoclasts during the osteolytic lesion. However, the specific molecules for the lung cancer cells to metastasize to the bone require further research and exploration. The present study aimed to investigate the relative molecular mechanisms of bone metastasis in lung cancer in recent years, providing a general understanding about the features of lung cancer preferences to bone, and discussing other things that require investigation.

Efficacy observation of zoledronic acid combined with chemotherapy in the treatment of bone metastases of lung cancer

目的 观察唑来膦酸联合化疗治疗非小细胞肺癌（NSCLC）骨转移的临床疗效。 方法 选取2014年8月至2015年8月收治的NSCLC骨转移患者60例，根据数字表法随机分为观察组与对照组，每组30例，对照组采用注射用盐酸吉西他滨联合顺铂治疗，观察组在此基础上联合唑来膦酸治疗。 结果 观察组患者疼痛缓解有效率为90.00 %（27/30），对照组为63.33 %（19/30），差异有统计学意义（P 0.05）。 结论 唑来膦酸联合化疗治疗NSCLC骨转移可有效降低患者的疼痛程度，改善活动能力，能很大程度地提高患者生命质量，值得临床进一步应用及推广。

Basigin-2 upregulated by receptor activator of NF-κB ligand enhances lung cancer-induced osteolytic lesions.

BackgroundLung cancer bone metastasis causes poor prognosis. Basigin-2, a novel cancer-associated biomarker, is upregulated in lung cancer and has been linked with tumor progression. But little is known about the role of basigin-2 in lung cancer bone metastasis and osteolytic lesion.MethodsBasigin-2 expression was evaluated in biopsy tissue specimens of 20 lung cancer patients with bone metastases via immunohistochemistry. Invasion assay and MTT proliferation assay were performed to test the invasion and proliferation of lung cancer cell after modulated basigin-2 expression. The osteoclastic activity of basigin-2 was detected in tibia cancer model by injected of lung cancer cells. The regulation role of receptor activator of NF-κB ligand (RANKL) on basigin-2 and its downstream molecules were measured by real-time quantitative RT-PCR, gelatin zymography and western blot analysis.ResultsWe found that basigin-2 was highly expressed in lung cancer bone metastases. Then, we demonstrated that basigin-2 could promote lung cancer cells invasion, metastasis and proliferation through upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression. The lung cancer cells overexpressing basigin-2 strongly induced the osteolytic lesions in immunodeficient mice, which were reduced by treatment with basigin-2 blocking antibody. Furthermore, we explored the enhanced basigin-2 molecular mechanism in lung cancer bone metastasis. Our results indicated the RANKL, pivotal for the control of bone resorption, could increase basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro.ConclusionsBasigin-2 upregulated by RANKL induces MMPs and VEGF, which may increase lung cancer cell metastasis ability and support osteoclastic activity. Thus, our data suggest important roles for basigin-2 in lung cancer-induced osteolytic lesion and implicate this protein potential application as a target for lung cancer bone metastasis therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-016-0302-9) contains supplementary material, which is available to authorized users.

Diagnostic value of bone metabolic markers for bone metastasis of non-small cell lung cancer analyzed by Logistic regression combined with ROC curve

Objective To investigate the diagnostic value of bone metabolic markers (BGP, β-CTX and PINP) for bone metastasis of non-small cell lung cancer (NSCLC) analyzed by Logistic regression combined with ROC curve. Methods A total of 65 patients with stage Ⅳ NSCLC were enrolled in this study. The patients were divided into two groups based on radiological imaging, includirg bone metastasis group (30 cases) and non-bone metastasis group (35 cases). The serum concentrations of BGP, β-CTX and PINP were measured by electrochemical method. Logistic regression and ROC curve were applied to analyze the data and evaluate the diagnostic values. Results The concentrations of β-CTX [(0.54±0.39) ng/ml] and PINP [(103.64±81.86) ng/ml] were significantly higher in bone metastasis group than those [(0.31±0.16) ng/ml and (48.37±27.76) ng/ml, respectively] in non-bone metastasis group (P 0.05). The area under the ROC curve (AUC) for β-CTX and PINP was 0.662 and 0.678, respectively. The AUC for the new predictive variables created by Logistic regression was 0.761. Conclusion Combined detection of β-CTX and PINP in the serum and application of Logistic regression combined with ROC curve analysis can increase diagnostic accuracy on bone metastasis of NSCLC. Key words: Carcinoma, non-small-cell lung; Neoplasms metastasis; β-isomerized C-terminal telopeptides of type Ⅰ collagen; N-terminal propeptide of type Ⅰ procollage; Logistic models; ROC curve