miR-195 Targets HDGF to inhibit proliferation and invasion of NSCLC cells

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death worldwide. MicroRNAs (miRNAs) play critical roles in the development and progression of NSCLC. miR-195 acts as a tumor suppressor in several cancers, however, its role in NSCLC is not well understood. Herein, we found that miR-195 was significantly decreased in both NSCLC tissues and cell lines. Forced expression of miR-195 significantly suppressed proliferation, migration, and invasion of NSCLC cells. Hepatoma-derived growth factor (HDGF) was identified as a target of miR-195 in NSCLC cells. Overexpression of HDGF dramatically abolished the tumor suppressive role of miR-195 in NSCLC cells. Our results demonstrated a tumor suppressive role of miR-195 in NSCLC, and suggested a potential therapeutic target for NSCLC.     

MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in human cancers. Increasing evidence shows that deregulation of miRNAs contributes to the development and progression of human non-small cell lung cancer (NSCLC). Here, we identified miR-186 as a tumor suppressor in NSCLC, which was decreased in NSCLC. Overexpression of miR-186 significantly inhibited proliferation, migration, and invasion of NSCLC cells. In addition, Rho-associated protein kinase 1 (ROCK1) was identified as a target of miR-186 in NSCLC cells. Restoration of ROCK1 remarkably reversed the tumor-suppressive effects of miR-186 on cell proliferation, migration, and invasion in NSCLC cells. Furthermore, ROCK1 was inversely correlated with miR-186 expression in NSCLC. Collectively, our data indicate that miR-186 functions as tumor suppressor in NSCLC by targeting ROCK1.     

Prognostic value of CD44 and CD44v6 expression in patients with non-small cell lung cancer: meta-analysis

We sought to clarify the prognostic value of CD44 in survival of patients with non-small cell lung cancer (NSCLC). We performed a meta-analysis of relevant literature to aggregate the available survival results, using studies published in English until March 2014. Eligible studies dealt with CD44, CD44 standard form (CD44s) and CD44 variant 6 (CD44v6), assessment in NSCLC patients on primary lesions and reported survival data according to CD44 and CD44 isoforms expression. We aggregated 10 trials (5 trials for CD44v6, 3 trials for CD44, and 2 trials for CD44s) comprising 1,074 patients, in this meta-analysis. The combined hazard ratio (HR) with CD44v6 and CD44s was 2.39 (95 % confidence interval (CI) 1.69–3.37) and 1.64 (95 % CI 1.06–2.52), respectively. It associated high CD44v6 and CD44s expression with poor survival in NSCLC patients. However, CD44 overexpression did not significantly correlate with survival in patients with NSCLC (HR 1.44; 95 % CI 0.72–2.89). Our meta-analysis shows that CD44v6 and CD44s overexpression indicates poor prognosis for NSCLC patients. However, the high CD44 expression is not significantly correlated with survival for patients with NSCLC.     

Polymorphisms in ERCC1 gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients

We analyzed the role of three common single-nucleotide polymorphisms (SNPs) of ERCC1 in predicting the tumor responses and the survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. One hundred ninety-two patients who were identified as stage IV or IIIB/A NSCLC were collected between January 2008 and December 2009. ERCC1 rs11615, rs3212986, and rs2298881 were selected and genotyped by MassARRAY® Analyzer 4 system. One hundred three (53.65 %) patients showed a CR and PR to chemotherapy, and 81 (42.19 %) patients died from NSCLC with the median OS of 35.82?±?15.19 months. Multivariate regression analysis showed that rs11615 TT genotype and T allele were associated with optimal response to chemotherapy, and rs3212986 AA and A allele were correlated with better response to chemotherapy. Cox regression showed that patients carrying the rs11615 TT genotype and T allele and the rs3212986 AA genotype and A allele were significantly associated with higher risk of death from NSCLC. In conclusion, ERCC1 rs11615 and rs3212986 polymorphism were associated with a poor response to chemotherapy and shorter survival time of advanced NSCLC. ERCC1 rs11615 and rs3212986 polymorphisms may be helpful for designing individualized cancer treatment for NSCLC patients.     

Proteasome inhibitor MG132 enhances the antigrowth and antimetastasis effects of radiation in human nonsmall cell lung cancer cells

The current treatment for advanced nonsmall cell lung cancer (NSCLC) remains unsatisfactory due to resistance to chemotherapy and ionizing radiation. The ubiquitin-proteasome system (UPS) regulates multiple cellular processes that are crucial for the proliferation and survival of all kinds of cells. Carbobenzoxyl-leucinyl-leucinyl-leucinal-H (MG132), a specific and selective reversible inhibitor of the 26S proteasome, represents a novel approach for cancer therapy. However, whether MG132 can potentiate the effect of radiation against the growth and metastasis of NSCLC is not clear. We found that MG132 inhibited the proliferation of human NSCLC cell lines (A549 and H1299) in a dose- and time-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Then MG132 at a nontoxic dose (100 nM) was selected for following studies. Pretreatment of A549 and H1299 cells with 100 nM MG132 before ionizing radiation (IR) potentiated the anticancer effect of IR. Moreover, pretreatment with 100 nM MG132 before IR-enhanced radiation induced cell cycle arrest by decreased CyclinD1 but increased Wee1 expression in A549 and H1299 cells. In addition, pretreatment of MG132 combined with IR significantly suppressed cell migration and invasion abilities in NSCLC cell lines, which was accompanied by decreased expression of matrix metalloproteinase (MMP)-2 and MMP-9 in NSCLC cell lines. Taken together, our results demonstrate that MG132 enhances the antigrowth and antimetastatic effects of irradiation in NSCLC cells by modulating expression of cell cycle and invasion- related genes.     

miR-195 inhibits the growth and metastasis of NSCLC cells by targeting IGF1R

MicroRNAs (miRNAs) are small, non-coding RNAs which act as oncogenes or tumor suppressors in multiple human cancers. Accumulating evidence reveals that aberrant expression of miRNAs contributes to the development and progression of non-small cell lung cancer (NSCLC). Here, we identified miR-195 as a tumor suppressor in NSCLC cells, whose expression level was dramatically decreased in both NSCLC tissues and cell lines. Ectopic expression of miR-195 suppressed NSCLC cell proliferation and metastasis-related traits in vitro. Insulin-like growth factor 1 receptor (IGF1R) was identified as a direct target of miR-195 in NSCLC cells. Furthermore, restoration of IGF1R remarkably attenuated the tumor suppressive effects of miR-195 on NSCLC cells. Our data suggest that miR-195 may be involved in the carcinogenesis of NSCLC partially by targeting IGF1R.     

Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer

The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3–7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies.     

Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion

Long non-coding RNAs (lncRNAs) have emerged as major players in governing fundamental biological processes, and many of which are misregulated in multiple cancers and likely to play a functional role in tumorigenesis. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. lncRNA associated with microvascular invasion in HCC (lncRNA MVIH) was found to be generally upregulated in HCC. Moreover, MVIH overexpression could serve as an independent risk factor to predict poor RFS and promote tumor growth and metastasis via activating angiogenesis. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression is unknown. In this study, we found that lncRNA MVIH levels were increased in NSCLC tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, tumor size, and lymph node metastasis. Moreover, patients with high levels of MVIH expression had a relatively poor prognosis. Furthermore, knockdown of MVIH expression by siRNA could inhibit cell proliferation and invasion, while ectopic expression of MVIH promoted cell proliferation and invasion in NSCLC cells partly via regulating MMP2 and MMP9 protein expression. Our findings present that increased lncRNA MVIH could be identified as a poor prognostic biomarker in NSCLC and regulate cell proliferation and invasion.     

The Application of Real-Time PCR Technique to Detect Rare Cell Clones with Primary T790M Substitution of EGFR Gene in Metastases of Non-small Cell Lung Cancer to Central Nervous System in Chemotherapy Naive Patients

The time-limited efficacy of reversible EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) with EGFR gene activating mutations is associated with development of treatment resistance after some period of therapy. This resistance predominantly results from secondary mutations located in EGFR gene, especially T790M substitution. There is limited information available concerning the prevalence of primary T790M mutations in patients with metastatic NSCLC tumors before treatment with EGFR-TKIs. The aim of work was to assess the prevalence of de novo T790M mutations in EGFR gene in tissue samples from NSCLC metastatases in central nervous system (CNS) in both chemotherapy and EGFR-TKI naive NSCLC patients. We analyzed DNA samples isolated from paraffin-embedded tissue from CNS metastases for T790M mutations using real-time PCR and TaqMan probe against the T790M mutant sequence. The tissue samples were taken during palliative neurosurgery in 143 NSCLC patients. Amplification of the T790M-specific sequence was detected in 25 patients (17.5 %). The quantity of mutated DNA was less than 1 % in all samples with amplification, and in vast majority (20 patients, 14 % of all samples) it was even less that 0.1 %. In 5 patients (3.5 %) quantity of mutated DNA ranged from 0.1 to 1 % and true positive results of T790M mutation presence in these patients were most possible. Amplification of this sequence was not concurrent with common EGFR mutations and was not associated with sex, smoking status and pathological type of cancer. There is a possibility to detect the primary T790M mutation in brain metastases of NSCLC in EGFR-TKIs naïve patients.     

Expression of TGFβ-1 and EHD1 correlated with survival of non-small cell Lung cancer

Transforming growth factor-β1 (TGFβ-1) signaling is regulated by endocytotic pathway. To clarify the prognostic value of TGFβ-1 and to verify the involvement of endocytosis in drug resistance, we examined the expression of TGFβ-1 and Eps15 homology domain 1 (EHD1) in non-small cell lung cancer (NSCLC) and its association with tumor characteristics and survival of patients with NSCLC. Expression of TGFβ-1 and EHD1 was evaluated by immunohistochemistry in paraffin sections from 105 NSCLC patients. Overall survival (OS) was analyzed by Kaplan–Meier method, log-rank test, and multivariate Cox proportional hazard regression model. Positive immunostaining of TGFβ-1 and EHD1 was detected in 52.38 and 39.05 % of NSCLC samples, respectively. In non-adjuvant chemotherapy-treated group (P?=?0.006) and epidermal growth factor receptor (EGFR) (+) group (P?=?0.038), patients with TGFβ-1 expression had a longer OS. EHD1 negative expression predicted a longer OS (P?=?0.003), especially in EGFR (+) (P?=?0.006) and adjuvant chemotherapy-treated patients (P?=?0.003). NSCLC patients with concurrent positive TGFβ-1 and negative EHD1 (combined markers) were significantly correlated with better OS (P?=?0.001). American Joint Committee on Cancer (AJCC) status and combined markers were independent prognostic indicators for OS (HR (95 % CI) 1.576 (1.112–2.232), P?=?0.011 and HR 0.349 (0.180–0.673), P?=?0.002, respectively). We identified concordant TGFβ-1 positive and EHD1 negative as a strong favorable prognosis factor in NSCLC. Our results may help us to select and optimize strategies for individualized therapy.     

The role of SHP-1 promoter 2 hypermethylation detection of lymph node micrometastasis in resectable stage I non-small cell lung cancer as a prognostic marker of disease recurrence

Background

Despite adequate surgical management of stage I non-small cell lung cancer (NSCLC), many patients still relapse. Nodal micrometastases which cannot be detected by the standard hematoxylin and eosin (H&E) method are the postulated mechanism. We conducted a study of an epithelial-specific methylation marker, SHP-1 promoter 2 (SHP1P2) methylation, as a potential molecular marker to determine its association with a high risk of disease relapse.

Material and method

Lymph nodes from stage II–IIIA NSCLC patients were examined to explore the potential role of SHP1P2 methylation in detecting metastatic carcinoma according to H&E staining. Further study was done in lymph nodes from stage I NSCLC patients who underwent curative resection and follow-up at The King Chulalongkorn Memorial Hospital, Bangkok, Thailand. No adjuvant treatment was given, according to the standard treatment in that stage. Patients who relapsed within 40 months after resection were defined as high risk.

Results

The nodal SHP1P2 methylation level from stage II–IIIA NSCLC patients was significantly higher in the metastasis group, median 674 [0–3536] ng, compared with the no metastasis group, median 230 [0–3832] ng (p = 0.004). One-hundred and ninety-eight lymph nodes from stage I NSCLC patients were analyzed, including hilar and mediastinal nodes. With a median follow-up period of 65 [46–109] months, high SHP1P2 methylation levels of more than 140 ng in hilar lymph nodes were associated with early relapse, with sensitivity and specificity of 85 and 54 %, respectively (hazard ratio 5.3; 95 % confidence interval 5.0–5.6; p < 0.0001).

Conclusion

A high level of SHP1P2 methylation of hilar lymph nodes from stage I NSCLC patients is associated with early relapse of disease.     

Gefitinib induces cytoplasmic translocation of the CDK inhibitor p27 and its binding to a cleaved intermediate of caspase 8 in non-small cell lung cancer cells

Background

The epidermal growth factor receptor (EGFR) represents one of the first rationally selected molecules for targeted therapy in non-small cell lung cancer (NSCLC). Gefitinib is a reversible and highly selective tyrosine kinase inhibitor that competitively blocks the binding of adenosine triphosphate to its binding site in the tyrosine kinase domain of the EGFR. It has been found that treatment with gefitinib induces cell cycle arrest and apoptosis in NSCLC cells harboring activating EGFR mutations. Despite its clinical relevance, however, the mechanism underlying gefitinib-induced apoptosis has remained largely unknown.

Methods

We used the gefitinib-sensitive NSCLC cell line HCC827, which harbors a deletion in exon 19 of the EGFR gene, to examine the effect of gefitinib on the apoptotic machinery.

Results

We found that gefitinib treatment caused the NSCLC cells to undergo apoptosis following activation of the caspase 8 cascade. Expression of p27, a cyclin-dependent kinase (CDK) inhibitor whose major target is the cyclin E/CDK2 complex, was found to increase during this process, and this increase was accompanied by translocation of p27 from the nucleus to the cytoplasm. Moreover, we found that cytoplasmic p27 bound to a cleaved intermediate (p43/p41) of caspase 8 and that inhibition of cytoplasmic translocation of p27 reduced gefitinib-induced cell death in HCC827 cells.

Conclusion

Based on our results, we conclude that gefitinib-induced apoptosis is mediated by the interaction of p27 and caspase 8 in NSCLC cells carrying an activating EGFR mutation.     

MicroRNAs as novel biomarkers in the diagnosis of non-small cell lung cancer: a meta-analysis based on 20 studies

The detection of microRNAs (miRNAs), particularly those obtained from the bloodstream, is an emerging method for diagnosing human cancers, including non-small cell lung cancer (NSCLC). However, studies on the accuracy of miRNAs detection in diagnosing NSCLC have yield inconsistent conclusions, making it necessary to conduct a meta-analysis to systematically evaluate the diagnostic value of miRNAs in the diagnosis of NSCLC. The Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), and Sinomed electronic databases were searched to identify all related articles evaluating the diagnostic value of miRNAs for NSCLC. A bivariate regression model was used to calculate the pooled diagnostic accuracy estimates. A total of 20 articles were included in this meta-analysis, involving 1,563 NSCLC patients and 1,060 healthy controls. Overall, our bivariate random effects meta-analysis yielded area under curve (AUC) of 0.85 (95 % CI: 0.82–0.88) with sensitivity of 76 % (95 CI: 72–80) and specificity of 80 % (95 % CI: 77–84) for the use of miRNAs in differentiating NSCLC patients from healthy controls. In addition, subgroup and meta-regression analyses revealed that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.89, 81, and 84, respectively) had a higher diagnostic accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.81, 73, and 77 %, respectively). Furthermore, a comparison of miRNAs expression patterns between blood and sputum samples provides additional evidence that miRNAs obtained from blood (AUC, sensitivity, and specificity of 0.86, 78, and 80 %, respectively) are more credible diagnostic biomarkers than those from sputum (AUC, sensitivity, and specificity of 0.79, 66, and 79 %, respectively). In summary, the current meta-analysis suggests that the detection of miRNAs may be used in the future as an initial screening test for NSCLC, particularly, the detection of a combination of multiple miRNAs, which is a more comprehensive indicator than individual miRNAs.     

ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway

ARMC8 proteins are novel armadillo repeat containing proteins, which are well conserved in eukaryotes and are involved in a variety of processes such as cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. Armadillo repeat proteins include well-known proteins such as β-catenin and p120ctn. Our current knowledge of ARMC8, especially its role in cancer, is limited. In this study, we quantified ARMC8 expression in 112 non-small cell lung cancer (NSCLC) tissues and adjacent non-cancerous tissues, and seven lung cancer cell lines using immunohistochemistry staining and Western blotting. ARMC8 level was significantly higher in NSCLC tissues than in the adjacent normal tissues (67.9 % versus 5.4 %, p?p?=?0.022), lymph node metastasis (p?=?0.001), and poor prognosis (p?NSCLC patients. Cox regression analysis demonstrated that ARMC8 was an independent prognostic factor for NSCLC. Consistent with this, ARMC8α downregulation by siRNA knockdown inhibited growth, colony formation, and invasion in A549 lung cancer cells, while ARMC8α overexpression promoted growth, colony formation, and invasion in H1299 lung cancer cells. In addition, ARMC8α knockdown downregulated canonical Wnt-signaling pathway activity and cyclin D1 and matrix metalloproteinase (MMP)-7 expression. Consistent with this, ARMC8α overexpression upregulated canonical Wnt-signaling pathway activity and cyclin D1 and MMP-7 expression. These results indicate that ARMC8α upregulates cyclin D1 and MMP7 expression by activating the canonical Wnt-signaling pathway and thereby promoting lung cancer cell proliferation and invasion. Therefore, ARMC8 might serve as a novel therapeutic target in NSCLC.     

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

Caveolin-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 (χ² = 200.478, p < 0.005), but the difference of expression level of Cav-1 is not significant (χ² = 2.248, p > 0.005) 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, 95 % 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 (95 % 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.     

Rare and complex mutations of epidermal growth factor receptor,and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer

Background

There are many complex and rare mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) other than the two classical mutations of L858R and exon 19 deletional mutation. The purpose of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs).

Methods

We analyzed 1,431 NSCLC patients who were treated with either gefitinib or erlotinib. Exons 18 to 21 of EGFR were analyzed by PCR and subjected to direct sequencing methods.

Results

Of 306 patients who had EGFR mutation, 24 patients (7.3 %) had complex mutations. The frequency of rare mutations was 10.3 %. Four groups were categorized [group A (N = 269): classical mutation alone; group B (N = 16): complex mutation with classical mutation; group C (N = 16): rare mutation alone or complex mutation with rare mutation; group D (N = 5); classical mutation with T790M]; the response rate (RR) to TKI was significantly different between each group (RR = 74.8 % in group A vs. 68.8 % in group B vs. 25.0 % in group C vs. 80.0 % in group D, P < 0.001). Progression-free survival (PFS) was also poorer in rare mutations (median PFS: 11.9 vs. 8.1 vs. 1.4 vs. 8.0 months, respectively, P < 0.001).

Conclusions

NSCLC patients harboring rare mutations did not show consistent and favorable responses to EGFR TKI compared with those harboring classical mutations. However, complex mutations with classical mutations showed similar treatment efficacy toward EGFR TKI to that with classical mutations alone.     

Long progression-free survival with first-line paclitaxel plus platinum is associated with improved response and progression-free survival with second-line docetaxel in advanced non-small-cell lung cancer

Purpose

Paclitaxel and docetaxel are two taxanes approved for the treatment of non-small-cell lung cancer (NSCLC). However, there is limited evidence regarding the efficacy of docetaxel in NSCLC previously treated with a paclitaxel–platinum doublet (PP). The aim of our study was to evaluate the response to docetaxel in NSCLC patients with prior PP treatment.

Methods

Patients with stage IV NSCLC treated with PP that presented disease progression and received docetaxel as second-line treatment were included. Demographics, clinical characteristics, EGFR mutation status, objective response (OR), overall survival (OS), progression-free survival (PFS), and PFS without chemotherapy after first line with PP were analyzed.

Results

Sixty-three patients were evaluated. Median age was 58 years, 54 % of patients were women, 53 % were never-smokers, and 39 % had EGFR mutations. OR and median PFS for PP were 36.5 % and 6.7 months, respectively. OR and median PFS for docetaxel were 19 % and 3.8 months, respectively. Patients with EGFR mutations had better response to docetaxel compared with wild-type patients (26 vs. 17 %, p = 0.028). However, only long PFS (>6 months) to first-line PP was independently associated with a higher OR [RR 6.3, 95 % CI (1.03–38.4), p = 0.046], and longer PFS [0.49 (0.25–0.9)] and OS [0.2 (0.06–0.7), p = 0.008] to second-line docetaxel compared with patients with short PFS (≤6 months) to PP.

Conclusions

Previous use of PP does not preclude a favorable response to docetaxel in NSCLC. Long PFS with PP may help select NSCLC patients who benefit from second-line docetaxel.     

Prognostic significance of preoperative serum carcinoembryonic antigen in non-small cell lung cancer: a meta-analysis

Observational studies on the prognostic role of preoperative serum carcinoembryonic antigen (CEA) in non-small cell lung cancer (NSCLC) are controversial. Electronic databases updated until June 1, 2014 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between preoperative serum CEA level and survival of patients with NSCLC. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 16 studies (n?=?4,296 patients) that evaluated the correlation between preoperative serum CEA level and survival in patients with NSCLC. Combined hazard ratios suggested that preoperative serum CEA overexpression was associated with poor prognosis of overall survival (OS) (hazard ratio (HR)?=?2.28, 95 % confidence interval (CI) 2.24–2.31) in patients with NSCLC. Meanwhile, for p-stage I NSCLC, the HR (95 % CI) was 1.98 (1.73–2.15). In the stratified analysis by patient source, significant risks were found among Asians and non-Asians. However, significant heterogeneity was observed among all studies. In the present meta-analysis, preoperative serum CEA overexpression indicates a poor prognosis for patients with NSCLC.