Non-bone Metastasis Group Research Articles

Establishment and verification of a predictive model for bone metastasis in patients with non-small cell lung cancer based on peripheral blood CX3CL and CCL28.

To establish a predictive model of bone metastasis in patients with non-small cell lung cancer (NSCLC) using peripheral blood CX3CL and CCL28, and to verify its application value. We retrospectively gathered clinical data from 210 patients with NSCLC treated at our institution between April 2021 and December 2023. These patients were stratified into two groups based on the presence of bone metastases: a bone metastasis group (n = 49) and a non-bone metastasis group (n = 161). A logistic regression model was developed to predict bone metastasis and to evaluate the model's predictive performance. Multivariate logistic regression analysis identified age (OR = 6.689, P < 0.001), carcinoembryonic antigen (CEA, OR = 5.699, P < 0.001), CX3CL1 (OR = 5.418, P < 0.001), and CCL28 (OR = 7.692, P < 0.001) as independent predictors of bone metastasis in NSCLC patients. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.794 for both the modeling and validation cohorts. Decision curve analysis (DCA) indicated a superior net benefit of the model. Calibration curves confirmed close concordance between predicted and observed probabilities of bone metastasis. The Hosmer-Lemeshow test yielded a chi-square statistic of 4.743 with a P-value of 0.178, suggesting a good fit. The predictive model utilizing serum levels of CX3CL1 and CCL28 demonstrates robust predictive accuracy and efficacy for bone metastasis in patients with NSCLC.

The clinical association between coagulation indexes, platelet-related parameters, and bone metastasis of newly diagnosed prostate cancer

BackgroundAt present, much evidence shows that many cancers have a high risk of thrombosis. Several studies have shown the prognostic value of platelet-related parameters and coagulation indexes in prostate cancer (PCa). However, the association between platelet-related parameters, coagulation indexes and bone metastasis of Pca is unclear.MethodsA total of 234 pathologically diagnosed patients with Pca were consecutively collected and stratified into the bone metastasis group and non-bone metastasis group according to the results of the bone scan. ROC curve analysis was used to explore the auxiliary predictive value of single and combined parameters for bone metastasis in Pca patients. Univariate and multivariate Logistic regression analyses were used to determine the relationship between platelet-related parameters, coagulation indexes, and bone metastasis of Pca.ResultsPlatelet count (PLT), fibrinogen (Fib), prostate-specific antigen (PSA), and D-dimer (DD) levels of the bone metastasis group were significantly higher than the non-bone metastasis group (P = 0.010, P < 0.001, P < 0.001, and P < 0.001, respectively). This study confirmed that PLT, PSA, DD and Fib have auxiliary predictive value for prostate cancer bone metastasis. After the combination of PLT, PSA, DD and Fib, the area under the curve, sensitivity and specificity increased significantly. The univariate logistic analysis demonstrated that PLT (OR: 1.008, P = 0.011), DD (OR: 2.690, P < 0.001), PSA (OR: 1.073, P < 0.001), Gleason score (OR: 7.060, P < 0.001), and Fib (OR: 2.082, P < 0.001) were significantly positively correlated with bone metastasis of Pca. Multivariate analysis showed that PSA (OR: 1.075, P < 0.001), DD (OR: 2.152, P < 0.001), Gleason score (OR: 2.904, P < 0.001), and Fib (OR: 1.706, P < 0.001) were independent risk factors for bone metastasis of Pca after adjusting for Age, BMI and other confounding factors.ConclusionsHigher platelet, D-dimer, prostate-specific antigen, Gleason score, and fibrinogen levels may predict a worse prognosis in patients with Pca. PLT, DD, and Fib, as readily available and relatively inexpensive indicators, help predict bone metastasis of Pca. It is suggested that PLT, DD and Fib may be helpful in the risk stratification of Pca.

Diagnosis of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer.

To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospitalof Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options.

Influencing Factors of Bone Metastasis in Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer and Efficacy of Capecitabine Plus Docetaxel

The clinical data characteristics of human epidermal growth factor receptor 2 negative breast cancer patients were analyzed to investigate the influencing factors of bone metastasis. A total of 754 patients with human epidermal growth factor receptor 2 negative breast cancer admitted to the First People's Hospital of Lianyungang from January 2017 to September 2022, including 273 patients in the bone metastasis group and 481 patients in the non-bone metastasis group, were retrospectively and systematically evaluated for their clinic pathological characteristics, treatment modalities and their influencing factors. Chi-square test and Mann-Whitney U test were used to calculate the differences in clinical data between patients with human epidermal growth factor receptor 2 negative bone metastases and those without bone metastases. Binary logistic regression was performed to analyses the risk factors for the development of bone metastases in human epidermal growth factor receptor 2 negative breast cancer. A significant difference was found between the patients in the bone metastasis group and the non-bone metastasis group in terms of T-stage, N-stage, estrogen receptor, progesterone receptor, tumour molecular classification, axillary lymph node metastasis and quality of life scores (functional assessment of cancer therapy-breast) after combined therapy with capecitabine plus docetaxel (Z=-2.706, Z=-2.864, χ2=75.954, χ2=55.618, χ2=114.854, χ2=305.211, χ2=66.945 and p<0.05), while statistical significance was absent in terms of age and location of the primary site (χ2=2.888, χ2=1.903 and p>0.05). Logistic regression analysis revealed that high T-stage, luminal A molecular staging and the occurrence of axillary lymph node metastases were all risk factors for bone metastases in human epidermal growth factor receptor 2 negative breast cancer patients (OR=4.352, 95 % CI=2.147 to 8.823, p<0.001; OR=0.281, 95 % CI=0.179 to 0.441, p<0.001 and OR=12.766, 95 % CI=6.712 to 24.283, p<0.001). The occurrence of bone metastases in human epidermal growth factor receptor 2 negative breast cancers was statistically correlated with T-stage, N-stage, estrogen receptor, progesterone receptor, molecular tumour staging, axillary lymph node metastasis and patient quality of life scores after combined therapy with capecitabine plus docetaxel. High T-stage, luminal A and axillary lymph node metastasis were all risk factors. Combined therapy of capecitabine and docetaxel provides significant efficacy in patients with human epidermal growth factor receptor 2 negative breast cancer bone metastases.

Retrospective analysis of risk factors for bone metastasis in newly diagnosed prostate cancer patients.

The aim of the study was to analyze the clinical data of newly diagnosed prostate cancer (PCa) patients with bone metastasis and to explore the relevant risk factors. The clinical data of 251 patients with PCa, who were initially diagnosed in our hospital from February 2015 to October 2021, were retrospectively analyzed. According to the whole-body bone scan results, patients were divided into the bone metastasis group (n = 66) and the non-bone metastasis group (n = 185). The patient's age, total prostate-specific antigen (TPSA), free PSA (fPSA), prostate volume, alkaline phosphatase (ALP), Gleason score, erythrocyte sedimentation rate (ESR), and pelvic lymph node metastasis were collected. Univariate correlation and multivariate regression analyses, together with receiver operating characteristic curve, were used to analyze PCa bone metastasis-related factors. The incidence of bone metastasis in newly diagnosed PCa was about 26.29% (66/251). Among them, the incidence of pelvic metastasis was the highest, at 78.78% (52/251), and multiple bone metastases were significantly higher than single bone metastasis (80.31% vs. 19.69%). Univariate correlation analysis indicated that age, Gleason score, ESR, TPSA, ALP, fPSA/PSA, capsular infiltration, and pelvic lymph node metastasis (p < 0.05) were highly correlated with PCa bone metastasis. Multivariate Logistic regression analysis showed that TPSA (95% CI: 0.977-1.284, p = 0.007), ALP (95% CI: 1.008-1.080, p = 0.016), Gleasons core (95% CI: 2.110-82.349, p = 0.006), ESR (95% CI: 1.062-1.104, p = 0.003), and pelvic lymph node metastasis (95% CI: 1.537--33.239, p = 0.012) were independent risk factors for bone metastasis of PCa. The cut-off values for TPSA, ALP, Gleason score, and ESR were 33.78 ng/ml, 73.65 U/L, 7.5, and 23.5 mm/h, respectively. Additionally, the respective sensitivities for TPSA, ALP, Gleason score, and ESR were 81.8%, 75.8%, 68.2% and 77.3%, and the respective specificities was 90.3%, 98.9%, 98.4%, and 74.6%. TPSA, ALP, Gleason score, ESR and pelvic lymph node metastasis are independent risk factors for bone metastasis of PCa.

Value of CT Radiomics and Clinical Features in Predicting Bone Metastases in Patients with NSCLC.

Objective To explore the CT radiomic features and clinical imaging features of the primary tumor in patients with nonsmall cell lung cancer (NSCLC) before treatment and their predictive value for the occurrence of bone metastases. Methods From June 2017 to June 2021, 195 patients with NSCLC who were pathologically diagnosed without any treatment in the Cancer Hospital Affiliated to Hainan Medical College were retrospectively analyzed, and they were divided into a bone metastasis group and a nonbone metastasis group. The relationship between clinical imaging features and bone metastasis in patients was analyzed by the t-test, rank sum test, and χ2 test. At the same time, ITK software was used to extract the radiomic characteristics of the primary tumor of the patients, and the patients were randomly divided into a training group and a validation group in a ratio of 7 : 3. The training model was validated in the validation group, and the performance of the model for predicting bone metastases in NSCLC patients was verified by the ROC curve, and a multivariate logistic regression prediction model was established based on the omics parameters extracted from the best prediction model combined with clinical image features. Results Seven features were screened from the primary tumor by LASSO to establish a model for predicting metastasis. The area under the curve was 0.82 and 0.73 in the training and validation sets. The best omics signature and univariate analysis suggested clinical imaging factors (P < 0.05) associated with bone metastases were included in multivariate binary logistic analysis to obtain clinical characteristics of the primary tumor such as gender (OR = 0.141, 95% CI: 0.022–0.919, P = 0.04), increased Cyfra21-1 (OR = 0.12, 95% CI: 0.018–0.782, P = 0.027), Fe content in blood (OR = 0.774, 95% CI: 0.626–0.958, P = 0.018), CT signs such as lesion homogeneity (OR = 0.052, 95% CI: 0.006–0.419, P = 0.006), pleural indentation sign (OR = 0.007, 95% CI: 0.001–0.696, P = 0.034), and omics characteristics glszm_Small Area High Gray Level Emphasis (OR = 0.016, 95% CI: 0.001–0.286, P = 0.005) were independent risk factors for bone metastasis in patients. Conclusion The prediction model established based on radiomics and clinical imaging features has high predictive performance for the occurrence of bone metastasis in NSCLC patients.

Single-center study of the abnormal concentration of bone imaging agent and prostate cancer bone metastasis prediction model

Objective: To investigate the relationship between total prostate specific antigen (TPSA), free prostate specific antigen/total prostate specific antigen [RAT (F/T)], Gleason score, other factors and the whole-body bone plane imaging which was used to evaluate the bone metastasis of prostate cancer (PCa), and the diagnostic value of the abnormal concentration of bone imaging agent for single lesion. Methods: A retrospective analysis of (99)Tc(m)-methylene diphosphonate ((99)Tc(m)-MDP) whole-body bone imaging data of 93 patients with confirmed PCa in The First Hospital of Shanxi Medical University from Jan 2018 to Jan 2019 was conducted. The bone metastasis was diagnosed by whole-body bone imaging. The factors related to PCa bone metastasis, including age, TPSA, RAT (F/T), Gleason score were analyzed by Chi-square test and logistic two-class regression. The optimal cut-off point of TPSA was defined by receiver operating characteristic (ROC) curve. The region of interest (ROI) technique was used to repeatedly delineate the lesion (T) and the background area (NT) outside the bone and calculate the abnormal concentration value of bone imaging agent (T-NT)/NT, and the ROC curve was used to determine its diagnostic value. Results: The result of Chi-square analysis showed that Gleason score, TPSA and RAT (F/T) were associated with bone metastasis (P<0.05). Logistic regression analysis showed that TPSA and RAT (F/T) were associated with bone metastasis (P<0.01). TPSA >92.82 ng/ml was the best diagnosis for bone metastasis, and the sensitivity and specificity were 77.1% and 81.0%, respectively. There were 320 sites of high concentration of imaging agents in the whole-body bone imaging of PCa patients (194 in the metastatic group and 126 in the non-metastasis group). The (T-NT)/NT in the bone metastasis group was 7.11±0.29, the non-bone metastasis group was 2.69±0.20. (T-NT)/NT >3.52 was the best diagnosis for bone metastasis of single lesion, and the sensitivity and specificity were 86.1% and 80.2%, respectively. Conclusions: Gleason score, RAT (F/T) and TPSA are important risk factors of PCa bone metastasis. TPSA >92.82 ng/ml is the most supportive diagnosis for PCa bone metastasis. The abnormal concentration of bone imaging agent >3.52 owns the best diagnosis effect for the single lesion of PCa.

The Construction and Analysis of ceRNA Network and Patterns of Immune Infiltration in Mesothelioma With Bone Metastasis.

Background: Mesothelioma is a rare and aggressive tumor. Bone metastasis often occurs in the later stages of this disease along with poor quality of life. Thus, it is important to explore the tumorigenesis and bone metastasis mechanism of invasive mesothelioma. For this purpose, we established two nomograms based on tumor-infiltrating immune cells and ceRNA networks to describe the molecular immunity and the clinical prediction of mesothelioma patients with bone metastasis.Method: The expression profiles of mRNAs, lncRNAs, and miRNAs of 87 primary mesotheliomas were obtained from the TCGA database; there were four patients with bone metastasis and 83 patients without. We constructed a ceRNAs network based on the differentially expressed RNAs between mesothelioma and bone metastasis. CIBERSORT was used to distinguish 22 immune cell types from the tumor transcriptomes. Kaplan–Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of each factor. Prognosis-associated immune cells and ceRNAs were applied to establish prediction nomograms. The receiver operating characteristic curves (ROC) and calibration curves were utilized to assess the discrimination and accuracy of the nomogram.Results: Differential analysis revealed that 20 lncRNAs, 15 miRNAs, and 230 mRNAs were significantly different in mesothelioma samples vs. bone metastasis samples. We constructed the ceRNA network to include 10 protein-coding mRNAs, 8 lncRNAs, and 10 miRNAs. Nine of 28 ceRNAs were found to be significant in the Kaplan–Meier analysis. Out of the 22 cell types, the fraction of dendritic cells resting (P = 0.018) was significantly different between the bone metastasis group and the non-bone metastasis group. The ROC and the calibration curves, based on ceRNA networks and tumor-infiltrating immune cells, respectively, suggested acceptable accuracy (AUC of 3-year survival: 0.827, AUC of 5-year survival: 0.840; AUC of 3-year survival: 0.730; AUC of 5-year survival: 0.753). Notably, based on the co-expression patterns between ceRNAs and Immune cells, we found that the hsa-miR-582-5p, CASP9, dendritic cells resting, ANIX2, T cells CD8, and T cells CD4 memory resting might be associated with the mesothelioma bone metastasis.Conclusion: Based on ceRNA networks and patterns of immune infiltration, our study provided a valid bioinformatics basis in order to explore the molecular mechanism and predict the possibility of mesothelioma bone metastasis.

The Construction and Analysis of ceRNA Network and Patterns of Immune Infiltration in Mesothelioma with Bone Metastasis

Mesothelioma is a rare and aggressive tumor. Bone metastasis often occurs at the late-stage of this disease with poor quality of life. Thus, it is important to explore the tumorigenesis and bone metastasis mechanism of invasive mesothelioma. For this purpose, we downloaded the expression profiles of mRNAs, lncRNAs and miRNAs of 87 primary mesotheliomas were obtained from the TCGA database, including 4 patients with bone metastasis and 83 patients without it. Differential analysis revealed that 20 lncRNAs, 15 miRNAs and 230 mRNAs were significantly different in mesothelioma samples versus bone metastasis samples. We constructed the ceRNA network including 10 protein-coding mRNAs, 8 lncRNAs and 10 miRNAs. CIBERSORT was used to distinguish 22 immune cell types from the tumor transcriptomes. We established two nomograms based on tumor-infiltrating immune cells and ceRNA networks. Nine of 28 ceRNAs were found to be significant in Kaplan-Meier analysis. Out of the 22 cell types, the fraction of dendritic cells resting (P = 0.018) was significantly different between bone metastasis group and non-bone metastasis group. The ROC and the calibration curves based on ceRNA networks and tumor-infiltrating immune cells suggested acceptable accuracy respectively (AUC of 3-year survival: 0.827, AUC of 5-year survival: 0.840; AUC of 3-year survival: 0.730; AUC of 5-year survival: 0.753). Notably, based on the co-expression patterns between ceRNAs and Immune cells, we found that the hsa-miR-582-5p, CASP9, dendritic cells resting, ANIX2, T cells CD8 and T cells CD4 memory resting might associated with the mesothelioma bone metastasis. Funding: This work was supported by grants from the Natural Science Foundation of China (Grant No. 81702659; 81772856; 81501203), Youth Fund of Shanghai Municipal Health Planning Commission (No.2017YQ054) and Henan medical science and technology research project (Grant No. 201602031). Declaration of Interest: The authors declare no conflicts of interest in this work. Ethical Approval:The relevant data provided by TCGA are publicly available and do not require the approval of the local ethics committee.

Study on diagnostic value of P1NP and β-CTX in bone metastasis of patients with breast cancer and the correlation between them.

This study aimed to investigate the diagnostic value of the total amino-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of β-I collagen (β-CTX) in bone metastasis of patients with breast cancer and the correlation between them. The medical records of 73 patients were retrospectively analyzed. These patients with breast cancer were treated in Oncology, General Surgery, and Orthopedic Departments in The Third People's Hospital of Qingdao from March 2014 to April 2017, including 40 patients with bone metastasis (bone metastasis group) and 33 patients with no bone metastasis (non-bone metastasis group). Other 40 healthy people who received physical examination in the same period were selected as the control group. The expression of P1NP and β-CTX in plasma were detected by the Enzyme-linked immunosorbent assay, and the correlation between them was analyzed. There were significant differences in P1NP and β-CTX concentrations among the three groups (p<0.05). The concentrations of P1NP in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p<0.05); the concentrations of β-CTX in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p<0.05). P1NP: AUC=0.852, sensitivity: 72.5%, specificity: 93.9%, CUT OFF=66.44. β-CTX: AUC=0.883, sensitivity: 85.0%, specificity: 84.8%, CUT OFF=69.8. Joint detection: AUC=0.952, sensitivity: 84.8%, specificity: 99.5%, CUT OFF=99.5. The results of the concentrations of P1NP and β-CTX in the bone metastasis group detected by the Pearson correlation analysis showed that their concentrations were positively correlated in the bone metastasis group (r=0.764, p<0.05). P1NP and β-CTX in plasma have a high diagnostic value for bone metastasis of breast cancer and have important significance in the diagnosis of bone metastasis and disease monitoring.

Increased serum levels of miR-214 in patients with PCa with bone metastasis may serve as a potential biomarker by targeting PTEN.

MicroRNAs (miRNAs/miRs) are identified to serve key functions in the progression of various tumors. miR-214 is aberrantly expressed in various types of cancer. In the present study, the function of miR-214 and its feasibility as a potential non-invasive biomarker for patients with prostate cancer (PCa) in a hyperplasia group and a control group were investigated. First, RNA was isolated from the serum of 75 patients with PCa with bone metastasis, 65 patients with PCa with no bone metastasis and 70 healthy controls. The level of miR-214 expression was significantly upregulated in the serum of the bone metastasis group compared with the healthy control and non-bone metastasis groups. Expression levels of alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) were also evaluated. The results indicated that serum levels of BSP, ALP and ICTP were increased in the bone metastasis group compared with that in the non-bone metastasis group, hyperplasia group and the control group (P<0.05). The expression level of miR-214 is positively associated with poorly differentiated tumors in patients with PCa with a Gleason score >7 (P<0.05). Western blot analysis demonstrated that phosphatase and tensin homolog (PTEN) was a target gene of miR-214. Additionally, silencing of PTEN significantly increased the invasive ability of PC3 cells even when miR-214 expression was inhibited. In summary, serum miR-214 expression may serve as a potential novel non-invasive biomarker for PCa screening through targeting PTEN.

Risk Factors of Non-small Cell Lung Cancer with Bone Metastasis after Therapy

背景与目的肺癌目前是死亡率最高的肿瘤, 非小细胞肺癌(non-small cell lung cancer, NSCLC)患者在手术后通常会发生远处转移, 如骨转移、脑转移、肺转移等。本研究旨在探究NSCLC患者术后发生骨转移的危险因素。方法选择本院于2009年5月-2011年5月确诊收治的NSCLC患者176例, 按照是否发生骨转移将患者分为两组, 即骨转移组和无骨转移组。对比两组患者的一般临床病理资料, 并通过多因素分析对比发生骨转移的独立危险因素。结果NSCLC患者的一般临床病理资料中血栓与否, 肿瘤-淋巴结-转移(tumor-node-metastasis, TNM)分期与是否发生骨转移关系密切, 有统计学意义(均P < 0.01);在两组患者的凝血功能指标中发现凝血酶原时间、活化部分凝血酶活酶时间、纤维蛋白原、凝血酶时间、血小板计数、D-二聚体以及碱性磷酸酶之间存在明显的差异性, 有统计学意义(均P < 0.05);Logistic回归分析发现纤维蛋白原、碱性磷酸酶、T4期、N3期和D-二聚体为NSCLC患者发生骨转移的独立危险因素。结论纤维蛋白原、活化部分凝血酶活酶时间、碱性磷酸酶、T3期、N2期和D-二聚体为NSCLC患者发生骨转移的独立危险因素。

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and carboxyterminal cross-linked telepeptide of type I collagen in malignant tumor patients with bone metastasis

OBJECTIVETo investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal cross-linked telepeptide of type I collagen (ICTP), in cancer patients with bone metastasis. METHODSPatients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTSA significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSIONYishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

Association of the expression of leptin and leptin receptor with bone metastasis in pulmonary adenocarcinoma

Objective: To explore the association of expression of leptin and leptin receptor (LR) with bone metastasis of pulmonary adenocarcinoma. Methods: One hundred and sixteen pulmonary adenocarcinoma patients who had complete clinicopathological data and definite pathological diagnosis in our hospital from January 2008 to January 2010 were selected. They were divided into the metastasis (n= 58) and non-metastasis (control, n=58) groups. The expressions of leptin and LR were identified by immunohistochemistry. The differences between expressions of leptin and LR in primary pulmonary adenocarcinoma tissues and metastasis, and between the groups with and without bone metastasis were analyzed. We also analyzed the correlation of leptin and LR expressed in primary adenocarcinoma and bone metastatic tissues, and the relationship between their expression levels and bone metastasis free survival (BMFS). Results: Among 58 patients of the metastasis group, the cases of high, moderate and low expressions of leptin were 36, 15 and 7, respectively, and the cases of high, moderate and low expressions of LR were 32, 17 and 9, respectively. Among the 58 patients of control group, the cases of high, moderate and low expressions of leptin were 19, 24 and 15, respectively, and those of LR were 17, 16 and 25, respectively. The expressions of leptin and LR in primary pulmonary adenocarcinoma tissues of metastasis group were significantly different from those of the control group (P=0.006, P=0.002, respectively). The expressions of leptin and LR in primary pulmonary adenocarcinoma tissues of the bone metastasis group were also significantly different from those of the non-bone metastasis group (P=0.029, P=0.032, respectively). The high/moderate expression rates of leptin and LR in the bone-metastatic tissues reached 91.4% (32/35) and 88.6% (31/35), respectively. The results showed that the expressions of leptin and LR in primary pulmonary adenocarcinoma tissues were positively related with their expressions in bone metastatic tissue (r = 0.612). The median bone metastasis free survival (BMFS) of the bone metastasis groups with high, moderate and low expressions of leptin were 14, 21 and 47 months, respectively, and the median BMFS of high, moderate and low expressions of LR in the bone metastasis group were 13, 19 and 27 months, respectively. The expressions of leptin and LR in pulmonary adenocarcinoma were significantly associated with BMFS (P<0.001, P=0.006, respectively). Conclusions: The expressions of leptin and LR are significantly up-regulated in primary pulmonary adenocarcinoma tissues and bone metastatic tissues, and are negatively correlated with BMFS. These two molecules may be used as effective predictors of bone metastasis in pulmonary adenocarcinoma.

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

The effects of lung and prostate cancer bone metastasis on serum osteoprotegerin levels: a meta-analysis.

Bone metastasis leads to skeletal-related events in final-stage cancer patients. The incidence of prostate and lung cancers increases yearly; these cancers readily invade the bone. Some recent studies have found that serum osteoprotegerin (OPG) levels may be altered in patients with bone metastasis, whereas other reports have produced inconsistent findings. Hence, we conducted a meta-analysis to examine the effects of lung and prostate cancer on serum OPG levels. A systematic literature search was conducted using PubMed, Medline, and CNKI to identify relevant studies. A total of 11 studies were included. The standardized mean difference (SMD) and 95% confidence interval (95% CI) of the bone metastasis (BM) group, the non-bone metastasis (BM-) group and healthy controls were calculated. In prostate cancer, serum OPG levels in the BM group were higher than in the BM- group and healthy controls. Additionally, no significant difference in serum OPG levels was found between the BM- group and healthy controls. In lung cancer, serum OPG levels in the BM and BM- groups were significantly increased compared with healthy controls. However, no significant difference in serum OPG levels was found between the BM and BM- groups. Studies with larger sample sizes are required to confirm these findings.

Predictive value of serum bone sialoprotein and prostate-specific antigen doubling time in patients with bone metastasis of prostate cancer

This study aimed to evaluate the diagnostic and prognostic significance of serum bone sialoprotein (BSP) and prostate-specific antigen doubling time (PSADT) in patients with bone metastasis (BM) from prostate cancer (PC). A total of 116 patients with PC, 120 patients with benign prostatic hyperplasia (BPH) and 120 healthy controls were enrolled in this study. PC patients were divided into bone metastasis (BM) group (n=56) and non-bone metastasis (NBM) group (n=60). Serum BSP was detected by Sandwich ELISA. Severity of bone pain was evaluated using visual analogue score (VAS). Serum f-PSA and t-PSA levels were measured by using electrochemiluminescence immunoassay (ECLIA). PSADT was calculated according to the formula: PSADT=lg(2)/[log(PSA2)-log(PSA1)]. The mean serum BSP level in PC patients with BM was significantly higher than in PC patients without BM, BPH patients and controls (P<0.001 for all). Pearson's analysis showed that serum BSP level was positively correlated with VAS in PC patients with BM (P<0.05). Receiver operating characteristics (ROC) analysis demonstrated that BSP discriminated patients with BM from those without BM at the cutoff value of 33.26 ng/mL. The sensitivity and specificity were 78.21% and 79.28%, respectively. The optimal cutoff value of PSADT was 131 days, with sensitivity of 85.69% and specificity of 85.36%. Kaplan-Meier analysis revealed that subjects with higher BSP levels/shorter PSADT had a shorter BM-free period than those with lower BSP levels/longer PSADT. Serum BSP and PSADT are useful biomarkers for the diagnosis of BM from PC, and can be regarded as independent factors for predicting the prognosis of BM from PC. Combined determination of BSP and PSADT can improve accuracy and positive rate of BM from PC significantly.

Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer

BackgroundThis study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC).MethodsThe model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45) and non-bone metastasis group (other visceral metastasis and those without recurrence) (n = 60). Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC.ResultsThe molecular model for predicting bone metastasis was logit (P) = − 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253) demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency.ConclusionThe molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.

Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer

Osteopontin (OPN) plays important roles in tumor progression and metastasis through binding to OPN receptors such as alpha(v)beta(beta) integrin and CD44, and its overexpression in tumor is associated poor clinical outcome of NSCLC patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had not been treated for cancer at the time of sampling, were analyzed according to clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the OPN gene promoter. Advanced disease states had higher circulating levels of OPN (T4 versus T1-3, N3 versus N0-2, and M1 versus M0, P=.029, .001, and .001, respectively, Kruskal-Wallis H-test), reflected by higher level of OPN in stage IV than stage I-III (P=.029, Kruskal-Wallis H-test). Among the clinical and pathological parameters including age, gender, smoking status, histologic subtypes and grade of differentiation, smoking status influences circulating OPN level showing higher level of OPN in ex-smokers than current and non-smokers (P=.038, Kruskal-Wallis H-test). Variation at nucleotide (nt) -443 of the OPN gene promoter had no influence on circulating OPN levels, however, patients with G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA) NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only independent factor influencing circulating level of OPN. Although circulating level of OPN in the patients with bone metastasis was higher than in those without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in the OPN levels between bone metastasis group and non-bone metastasis group. Given that the elevated levels of OPN is associated with advanced stages of NSCLC, elucidating OPN regulatory mechanisms may contribute to the development of a new therapeutic modality for NSCLC.