Elevated matrix metalloproteinase-7 expression promotes metastasis in human lung carcinoma.

BACKGROUND: Matrix metalloproteinase 7 (MMP-7) promotes tumor invasion and metastasis in several cancers. However, its role in lung cancer progression is understudied. In this study, we investigated the correlation between MMP-7 expression and lung cancer pathology. METHODS: We searched the databases PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) for scientific literature relevant to MMP-7 and lung cancer. Carefully selected studies were pooled and ORs with 95% CI were calculated. Subgroup analyses and publication bias were analyzed to understand the retrieved data in greater detail. Version 12.0 STATA software was used for statistical analysis. RESULTS: We retrieved a total of 121 studies through database searches. Finally, 14 cohort studies satisfied our inclusion/exclusion criteria, and these 14 studies, published between 2004 and 2012, were selected for meta-analysis to understand the influence of MMP-7 expression in lung cancer progression. Our results showed consistent differences in MMP-7 expression when comparisons were made between TNM I-II versus III-IV (OR = 1.82, 95% CI: 1.19 to 2.78, P = 0.006); histologic grade 1 to 2 versus 3 to 4 (OR = 1.67, 95% CI: 1.14 to 2.42, P = 0.008); and lymph node-negative versus lymph node-positive samples (OR = 2.81, 95% CI: 1.73 to 4.58, P <0.001), with significantly higher MMP-7 expression levels found in the more advanced stages. Subgroup analysis showed that age was not the factor influencing the associations between histologic grade, LN metastasis and MMP-7 expression in lung cancer patients, as both under 60 and over 60 age groups showed strong correlations (all P <0.05). However, when TNM staging was analyzed for its association with MMP-7 expression, only patients under age 60 showed a statistically significant correlation. CONCLUSIONS: Our meta-analysis results revealed that MMP-7 overexpression is associated with advanced TNM and histological grades, and is linked to aggressive LN metastasis in lung cancer patients; thus MMP-7 is a useful biomarker to assess the disease status in lung cancers.

Roles of osteopontin and matrix metalloproteinase-7 in occurrence, progression, and prognosis of nonsmall cell lung cancer.

BACKGROUND: This study detected osteopontin (OPN) and matrix metalloproteinase-7 (MMP-7) expressions to explore the roles of OPN and MMP-7 in the occurrence, progression, and prognosis of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective study was conducted on NSCLC tissues (n = 152; case group) and adjacent nonneoplastic lung parenchyma (adjacent to tumor >5 cm; n = 152; control group) collected from 152 NSCLC patients. The protein expressions of OPN and MMP-7 were detected by immunohistochemistry. OPN and MMP-7 messenger RNA (mRNA) expressions were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The protein and mRNA expressions of OPN and MMP-7 in NSCLC tissues were evidently higher than those in adjacent nonneoplastic lung parenchyma (all P < 0.05). OPN protein and mRNA expression were associated with the degree of differentiation, tumor node metastasis (TNM) staging, and lymph node metastasis in NSCLC (all P < 0.05). MMP-7 protein expression was associated with TNM staging and lymph node metastasis (both P < 0.05) while MMP-7 mRNA expression was associated with the degree of differentiation, TNM staging, and lymph node metastasis (all P < 0.05). A significantly positive relativity was revealed between OPN expression and MMP-7 expression (protein: r = 0.789, P < 0.001; mRNA: r = 0.377, P < 0.001). Lymph node metastasis, TNM staging, OPN, and MMP-7 protein expressions were independent risk factors for the prognosis of NSCLC (all P < 0.05). CONCLUSION: High MMP-7 and OPN protein expressions are closely related to the occurrence, progression, and prognosis of NSCLC, and can be served as unfavorable prognostic factors for NSCLC.

Betulin inhibits lung carcinoma proliferation through activation of AMPK signaling.

Betulin (lup-20(29)-ene-3ß, 28-diol) is an abundant, naturally occurring triterpene. It is commonly isolated from the bark of birch trees and forms up to 30% of the dry weight of the extractive. In the present study, we revealed its antiproliferative effects and mechanisms using two lung carcinoma cells (A549 and NCI-292). By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine (BrdU) incorporation assays, we found that betulin could efficiently inhibit cell growth and proliferation. Besides, several key genes of cell-cycle regulators were also affected by betulin treatment. At the molecular level, our results demonstrated that treatment with betulin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in these cells. In agreement, inhibition of AMPK signaling largely reversed the antiproliferative roles of betulin. Taken together, these data provide evidence for a mechanism that may contribute to the antineoplastic effects of betulin and justify further work to explore its potential roles in lung cancer prevention and treatment.

A nomogram for predicting cerebral white matter lesions in elderly men.

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

Concentrations of vanadium in urine and seminal plasma in relation to semen quality parameters, spermatozoa DNA damage and serum hormone levels.

Widespread human exposure to vanadium has been well documented. Vanadium exposure was reported to induce male reproductive toxicity in toxicological studies, yet human epidemiologic studies are lacking. Here we determined the associations between environmental exposure to vanadium and semen quality, spermatozoa DNA damage and serum reproductive hormones. Concentrations of vanadium in seminal plasma and repeated urine samples were determined among 764 men recruited from a reproductive medicine centre. Associations of vanadium concentrations with semen quality parameters (n = 764), DNA integrity measures (n = 404) and serum reproductive hormones (n = 381) were assessed by logistic or linear regression models with adjustment for potential confounders. Significant positive dose-response relationships were observed between vanadium concentrations in seminal plasma and tail length and serum estradiol, as well as odds ratios for a below-reference-value sperm concentration; whereas inverse relationships between seminal plasma vanadium with total testosterone (T) and free T (all p values for trends <0.05) were observed. These relationships were maintained after adjusting for seminal plasma concentrations of other elements (i.e., arsenic, cadmium, copper, selenium, or tin). No significant associations was revealed between urinary vanadium concentrations and semen quality, spermatozoa DNA integrity and reproductive hormones. Our findings suggested that elevated vanadium exposure may be adversely associated with male reproductive health, and that seminal plasma vanadium may be a more direct exposure biomarker for the male reproductive system than urinary vanadium.

Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC.

Serum Osteopontin Levels Correlate with Clinical and Pathological Features in Non-Small Cell Lung Cancer.

OBJECTIVE: A metaanalysis was performed to investigate the association between serum osteopontin (OPN) levels and the clinical pathological features in non-small cell lung cancer (NSCLC) patients. STUDY DESIGN: A systematic literature search was performed to identify relevant studies published prior to September 2014 using PubMed and China National Knowledge Infrastructure databases. Data extracted from the selected studies were analyzed using statistical software. RESULTS: Based on our stringent selection criteria only 10 studies contained a combined total of 1,135 NSCLC patients. Our metaanalysis results clearly showed a strong correlation between serum OPN levels and multiple tumor parameters, such as TNM stage, histologic grade, and lymph node metastasis in NSCLC (TNM stage: RR = 0.69, 95% CI 0.62-0.77, p < 0.001; histologic grade: RR = 1.24, 95% CI 1.04-1.48, p = 0.016; lymph node metastasis: RR = 1.69, 95% CI 1.48 - 1.93, p < 0.001). CONCLUSION: Our findings revealed that serum OPN levels strongly correlate with clinical and pathological features in NSCLC patients.

Common variations of DNA repair genes are associated with response to platinum-based chemotherapy in NSCLCs.

AIM: Individual differences in chemosensitivity and clinical outcome of non-small-cell lung cancer (NSCLC) patients may be induced by host inherited factors. We investigated the impact of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln gene polymorphisms on the efficacy of platinum-based chemotherapy in NSCLC patients. METHODS: A total of 496 were consecutively selected from the Affiliated Hospital of Nantong University between Jan. 2003 and Nov. 2006, and all patients were followed-up until Nov. 2011. The genotyping of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted by duplex polymerase-chain-reaction with the confronting-two-pair primer methods. RESULTS: Individuals with XPD 312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy when compared with the wild- type genotype, with adjusted ORs(95% CI) of 0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regression showed the median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T genotype to be significantly lower than those with wild-type homozygous genotype. CONCLUSION: We found polymorphisms in XPD to be associated with response to platinum-based chemotherapy in NSCLC, and our findings provide information for therapeutic decisions for individualized therapy.