Dali Chen

Prognostic factors for resection of isolated pulmonary metastases in breast cancer patients: a systematic review and meta-analysis

BACKGROUNDnLung is a common organ of metastases in patients with primary breast cancer. Pulmonary metastasis of primary breast cancer is usually considered as a systemic disease, however, the systemic approaches have achieved little progress in terms of prolonging survival time. In contrast, some studies revealed a probable survival benefit of pulmonary metastasectomy for such patients. However, the prognostic factor for pulmonary metastasectomy in breast cancer patients is still a controversial issue. The aim of this study was to conduct a systematic review and meta-analysis of cohort studies to assess the pooled 5-year overall survival (OS) rate and the prognostic factors for pulmonary metastasectomy from breast cancer.nnnMETHODSnAn electronic search in MEDLINE (via PubMed), EMBASE (via OVID), CENTRAL (via Cochrane Library), and Chinese BioMedical Literature Database (CBM) complemented by manual searches in article references were conducted to identify eligible studies. All cohort studies in which survival and/or prognostic factors for pulmonary metastasectomy from breast cancer were reported were included in the analysis. We calculated the pooled 5-year survival rates, identified the prognostic factors for OS and combined the hazard ratios (HRs) of the identified prognostic factors.nnnRESULTSnSixteen studies with a total of 1937 patients were included in this meta-analysis. The pooled 5-year survival rates after pulmonary metastasectomy was 46% [95% confidence interval (95% CI): 43-49%]. The poor prognostic factors were disease-free interval (DFI) (<3 years) with HR =1.70 (95% CI: 1.37-2.10), resection of metastases (incomplete) with HR =2.06 (95% CI: 1.63-2.62), No. of pulmonary metastases (>1) with HR =1.31 (95% CI: 1.13-1.50) and the hormone receptor status of metastases (negative) with HR =2.30 (95% CI: 1.43-3.70).nnnCONCLUSIONSnSurgery with a relatively high 5-year OS rate after pulmonary metastasectomy (46%), may be a promising treatment for pulmonary metastases in the breast cancer patients with a good performance status and limited disease. The main poor prognostic factors were DFI (<3 years), resection of metastases (incomplete), No. of pulmonary metastasis (>1) and hormone receptor status of metastases (negative). And prospective randomized trials will be needed to address these issues in the future.

Fibroblast phenotypes in different lung diseases

BackgroundThe “seed and soil” hypothesis emphasizes the importance of interactions between tumor cells and their microenvironment. CAFs (Cancer associated fibroblasts) are important components of the tumor microenvironment. They were widely involved in cancer cells growth and metastasis. Fibroblasts may also play a role in inflammatory disease. The phenotype conversion of fibroblasts in lung diseases has not been investigated previously. We hypothesized that fibroblasts phenotypes may vary among different types of lung disease.MethodsThe study included six types of lung tissues, ranging from normal lung to lung adenocarcinoma with lymphatic metastasis. Para-carcinoma tissues which were 2-cm-away from the tumor focus were also included in the analysis. The expression of target proteins including alpha-SMA (smooth muscle actin), FAP (fibroblast activation protein), vimentin, E-cadherin, and CK-19 (cytokeratin-19) were examined by immunohistochemistry. TGF-beta(transforming growth factor) and Twist were detected simultaneously in all samples.ResultsA progressive increase in the levels of alpha-SMA, vimentin and CK-19 was observed in correlation to the degree of malignancy from normal lung tissue to lung adenocarcinoma with lymphatic metastasis, whereas E-cadherin expression showed the opposite trend. TGF-beta and Twist were detected in cancer tissues and inflammatory pseudotumors. None of the proteins were detected in para-carcinoma tissues.ConclusionsFibroblast phenotypes varied according to the type and degree of lung malignancy and fibroblasts phenotypic conversion occurs as a gradual process with specific spatiotemporal characteristics. Similar fibroblast phenotypes in inflammatory diseases and cancer tissues suggested a correlation between inflammation and cancer and implied a common mechanism underlying the formation of fibroblasts in inflammatory diseases and lung cancer.

Duplex value of caveolin-1 in non-small cell lung cancer: a meta analysis

AbstractnCaveolin-1 (Cav-1) may act as a prognostic biomarker in human cancers. This study is prepared to clarify the prognostic value of Cav-1 in patients with non-small cell lung cancer (NSCLC). All eligible articles from China National Knowledge Infrastructure, Pubmed, Highvire, and Science Direct systems were incorporated into this study. We extracted the patients’ clinical characteristics and survival outcomes and performed a meta-analysis to demonstrate the prognostic role of Cav-1 and the correlations between Cav-1 expression and clinical characteristics. Thirteen articles met the inclusion/exclusion criteria. Cav-1 is deregulated in human lung cancers (NSCLC and small cell lung cancer) compared to noncancerous tissues (χ2xa0=xa0200.478, pxa0<xa00.005), but the difference of expression level of Cav-1 is not significant (χ2xa0=xa02.248, pxa0>xa00.005) among different types of NSCLC, such as adenocarcinomas (ADs), squamous cell carcinoma (SCC) and miscellaneous cancers. Cav-1 expression could predict the poor prognosis of patients with NSCLC. The combined hazard ratio (HR, 95xa0% CI) was 2.00 (1.54, 2.60) for overall survival (OS) and 3.14 (1.68, 5.88) for progression free survival or disease free survival. The combined HR (95xa0% CI) of OS was 2.29 (1.26, 4.17) for ADs and 3.21 (1.69, 6.09) for SCC. The Cav-1 expression was associated with age, differentiation, primary tumor stage, tumor node metastasis stage, lymph node metastasis, chemotherapeutic response, and other clinical characteristics. We also analyzed the odds ratios of Cav-1 expression in AD and SCC patients by subgroups. Cav-1 plays a duplex role in tumorigenesis and tumor progression. Cav-1 may be another biomarker to predict the prognosis of lung cancers.

Unique trend and "contradictory trend" in discrimination of primary synchronous lung cancer and metastatic lung cancer

BackgroundDistinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Since genomic instability is a common feature of cancer, we hypothesized that independently arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. The feasibility of analyzing genomic instability expression profiles to distinguish multiple primary lung cancers from metastatic tumors was evaluated.MethodsThis study enrolled 13 patients, with multiple primary lung cancers demonstrating with the histology, who underwent surgery between April 2003 and December 2012 at the Department of the Thoracic Surgery at West China Hospital in Sichuan province of China and 10 patients who were diagnosed as metastasis disease during the same period for comparison purposes. Genomic DNA from lung cancers from individual patients was analyzed by six microsatellites (D2S1363, D6S1056, D7S1824, D10S1239, D15S822, and D22S689) with PCR to identify discordant allelic variation. The experiments were approved by the West China Hospital Ethics committee (No.2013 (33)) and all patients agreed to participate in the study and signed an informed consent form.ResultsAll of the 10 patients with distant metastasis showed a consistent consequence that we called “unique trend” between primary tumor and distant metastasis. The “trend” is representive in this study, which means that all alleles corresponding to six microsatellite markers were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors. In the group of synchronous lung tumor with different histological types, the result showed a “contradictory trend”. Some alleles were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors and other alleles corresponding to six microsatellite markers were detected in DNA from metastatic tumors but were reduced or not observed in DNA from primary tumors. In the third group (synchronous lung tumor with same histological types), 2 of 8 patients showed “unique trend” and the others showed “contradictory trend”.ConclusionsWith polymorphic microsatellite markers, the “unique trend” that represents metastasis cancers and the “contradictory trend” that represents primary multiple tumors are useful in the diagnosis between tumors found at the same time in the pulmonary even diagnosed with the histopathological evaluation from a single patient.

“Different trend” in multiple primary lung cancer and intrapulmonary metastasis

BackgroundThe distinguishing of intrapulmonary metastatic tumors from multiple primary lung cancers is difficult but of great importance for the therapeutic management and prognosis of these patients.MethodsWe used genomic DNA analyzed by six microsatellites (D7S1824, D15S822, D2S1363, D10S1239, D6S1056, and D22S689) with PCR to identify discordant allelic variation from 12 patients. There are five patients with multiple primary lung cancers and seven patients who were diagnosed with intrapulmonary metastases from 850 patients with primary lung cancer in our hospital. The experiments were approved by the West China Hospital Ethics committee (No. 2013 (33)) and all patients agreed to participate in the study and signed an informed consent form.ResultsIn the group of metachronous lung tumor, three of five patients have different histological types and one of five patients have the same histological type which showed “contradictory trend”. The other one showed “unique trend”. In the second group (intrapulmonary metastasis lung tumor), one patient showed “contradictory trend” and the others showed “unique trend”.Conclusions“Different trends” are useful in discrimination of intrapulmonary metastasis lung cancer and multiple primary lung cancer even diagnosed with the histopathological evaluation.

A novel differential diagnostic model for multiple primary lung cancer: Differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis

The incidence of synchronous multiple primary lung cancer (MPLC) is increasing. However, present diagnostic methods are unable to satisfy the individualized treatment requirements of patients with MPLC. The present study aimed to establish a quantitative mathematical model and analyze its diagnostic value for distinguishing between MPLC and cases of the histologically similar disease, intrapulmonary metastasis (IPM). The sum value of the differential expression ratios of four proteins, namely p53, p16, p27 and c-erbB2, was evaluated by immunohistochemically-staining specimens of primary cancers, second separate cancers, metastatic lymph nodes and metastatic cancers. The sum value of the differential expression ratio of the four proteins from the primary tumor and the lymph-node metastasis or metastatic cancer was <90 in the 11 patients with a single metastatic cancer and in the 30 patients with lymph-node metastasis, but was >90 in the 14 patients with different histological types of MPLC. Therefore, a quantitative differentially-expressed gene mathematical model was established as follows: Sum of the differential expression ratios = p16T1 − T + p27T1 − T2 + C-erbB2T1 − T2 + p53T1 − T2, where T1 is the primary cancer and T2 is the lymph node metastasis, metastatic cancer or the second separate cancer. The quantitative differentially-expressed gene mathematical model is considered to be a useful tool for distinguishing between MPLC and IPM.

Cross-talk between endothelial and tumor cells via basic fibroblast growth factor and vascular endothelial growth factor signaling promotes lung cancer growth and angiogenesis.

The present study aimed to investigate the origin and potential mechanisms of angiogenesis in lung cancer cells. Normal endothelial cells (ECs) were isolated from human umbilical vein ECs (HUVECs) and cultured. The human lung cancer A549 cell line was also used. The cross-talk model between the HUVECs and the A549 cell line was constructed in vitro using a Millicell co-culture system. Cluster of differentiation (CD)31 and CD146 were selected as markers of the HUVECs. CD105 was used as a marker of activated blood vessel ECs in the tumor microenvironment and glucose-regulated protein-78 (GRP-78) was used as a biomarker of the A549 cells. The four markers were detected by immunofluorescence, and the mean optical density was calculated. The growth curves were constructed using the cell proliferation reagent, WST-1. The expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the media was measured using an ELISA. The average proliferation rates of the co-cultured HUVECs and A549 cells were significantly higher than those observed in the control groups. The fluorescence intensity of CD105 expression in the co-cultured HUVECs was higher than that in the control group. The fluorescence intensity of GRP-78 in the co-cultured A549 cells was higher than that in the A549 cells cultured alone. The average expression levels of VEGF and bFGF in the co-cultured model were higher than in the control groups. Therefore, it was hypothesized that cancer cells may induce the differentiation of normal ECs into vascular ECs via the secretion of VEGF and bFGF. Furthermore, vascular ECs can affect the proliferation and differentiation of cancer cells.

Prognostic value of stromal decorin expression in patients with breast cancer: a meta-analysis

BACKGROUNDnNumbers of studies have investigated the biological functions of decorin (DCN) in oncogenesis, tumor progression, angiogenesis and metastasis. Although many of them aim to highlight the prognostic value of stromal DCN expression in breast cancer, some controversial results still exist and a consensus has not been reached until now. Therefore, our meta-analysis aims to determine the prognostic significance of stromal DCN expression in breast cancer patients.nnnMETHODSnPubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literatures met out inclusion criteria. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I(2) statistic were employed to estimate the level of heterogeneity across the included studies. Sensitivity analysis was conducted to further identify the possible origins of heterogeneity. The publication bias was detected by Beggs test and Eggers test.nnnRESULTSnThere were three English literatures (involving 6 studies) included into our meta-analysis. On the one hand, both the summarized outcomes based on univariate analysis (HR: 0.513; 95% CI: 0.406-0.648; P<0.001) and multivariate analysis (HR: 0.544; 95% CI: 0.388-0.763; P<0.001) indicated that stromal DCN expression could promise the high cancer-specific survival (CSS) of breast cancer patients. On the other hand, both the summarized outcomes based on univariate analysis (HR: 0.504; 95% CI: 0.389-0.651; P<0.001) and multivariate analysis (HR: 0.568; 95% CI: 0.400-0.806; P=0.002) also indicated that stromal DCN expression was positively associated with high disease-free survival (DFS) of breast cancer patients. No significant heterogeneity or publication bias was observed within this meta-analysis.nnnCONCLUSIONSnThe present evidences indicate that high stromal DCN expression can significantly predict the good prognosis in patients with breast cancer. The discoveries from our meta-analysis have better be confirmed in the updated review pooling more relevant investigations in the future.

Status and perspectives of detection by low-dose computed tomography or computed radiography in surgical patients with lung cancer, based on a five-year study

A retrospective study involving 502 lung cancer patients who had received pulmonary resection from 2009–2013 was conducted in order to compare the clinical characteristics of patients whose diagnosis was detected by low‐dose computed tomography (LDCT) and computed radiography (CR).

Refute the conclusion made by Jie et al. in "prognostic role of microRNA-100 in various carcinomas: evidence from six studies".

Recently, we had the honor of reading a meta-analysis article published in Tumor Biology which was completed by Jie et al. Because of our interest in the correlations between microRNAs (miRs) and human cancer prognosis, we carefully read the entire article. Jie et al. put forward a standpoint that deregulation of miR-100 in cancerous tissues could significantly predict poor survival in various carcinomas. The pooled hazard ratio (HR) with 95xa0% confidence interval (CI) was 2.19 (1.49–3.24, pu2009=u20090.0007). The reliability of the meta-analysis is reciprocally higher than traditional and narrative reviews. Furthermore, the reliability is exclusively dependent on reference retrieval, incorporating eligible articles as comprehensive as possible, and proper and accurate data extraction. We found several critical errors in their meta-analysis, and its conclusion was unbelievable and might misguide readers. According to their statistical strategies, we also conducted a meta-analysis to reevaluate the relationship between deregulation of miR-100 and human cancer prognosis for rectification. The present studies are not powerful enough to demonstrate the prognostic role of miR-100 in human cancers, and thus, much more works are needed in this field.