Prognostic Factor For Non-small Cell Lung Cancer Patients Research Articles

MiR-146b-5p functions as a suppressor miRNA and prognosis predictor in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. However, science has not yet been able to substantially improve the prognosis of lung cancer patients. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor development and metastasis. Expression of six miRNAs previously shown to play roles in tumor development (miR-146b-5p, miR-128b, miR-21, miR-221, miR-34a, and Let-7a) in other tumor types was examined using real-time RT-PCR in 78 specimens of NSCLC. The results revealed that patients with low expression of miR-146b-5p had significant shorter median and mean survival time than those with high miR-146b-5p expression (33.00 and 30.44 months versus 42.0 and 36.90 months, respectively; log-rank test P=0.048), thus low miR-146b-5p expression level was associated with poor prognosis in NSCLC patients. Univariate Cox hazard regression analysis demonstrated that miR-146b-5p expression levels tended to be a significant prognostic indicator of NSCLC (adjusted hazard ratio=0.482, 95% CI: 1.409- 29.593, P=0.016). Multivariate Cox proportional hazard regression analysis showed that miR-146b-5p expression levels were an independent prognostic factor for NSCLC patients (hazard ratio=0.259, 95% CI: 0.083-0.809, P=0.020). Furthermore, the effects of miR-146b-5p and miR-146b-3p on NSCLC cell growth and invasion in vitro were investigated. Our findings demonstrate that ectopic expression of miR-146b-5p suppressed cell proliferation, clonogenicity, migration/ invasion and also induced G1 arrest in vitro, but did not induce cell apoptosis; whereas enforced expression of miR-146b-3p did not have a significant effect on cell growth and metastasis. Further experiments indicated that miR-146b-5p could reduce mRNA levels of MMP16 and TRAF6 in vitro and was negatively related to the expression of TRAF6 in human NSCLC tissues. In a mouse model, Ago-miR-146b-5p could significantly inhibit the growth of lung cancer xenografts in nude mice. In conclusion, our findings demonstrate that miR-146b-5p functions as a suppressor miRNA and prognosis predictor in NSCLC.

Pituitary tumor transforming gene-1 in non-small cell lung cancer: Clinicopathological and immunohistochemical analysis.

Pituitary tumor transforming gene-1 (PTTG1) is a novel oncogene and overexpressed in a wide variety of human cancers. However, the clinical and prognostic significance of PTTG1 in non-small cell lung cancer (NSCLC) is still unknown. The expression status of PTTG1 in NSCLC at the publicly available GEO databases (GSE19804) was observed. The mRNA and protein expression of PTTG1 in NSCLC tissues and cell lines was detected by qRT-PCR and Western blot, and the association between PTTG1 expression and clinicopathological factors was analyzed by immunohistochemistry. In our Results, PTTG1 was one of genes overexpressed in NCSLC samples compared with paired adjacent normal lung samples in microarray data (GSE19804). PTTG1 mRNA and protein expressions were increased in NSCLC tissues and cell lines. PTTG1 protein expression was correlated with malignant status and poor prognosis of NSCLC patients. In conclusion, PTTG1 is correlated with NSCLC progression and as an independent poor prognostic factor in NSCLC patients.

Assessing PDL-1 and PD-1 in Non–Small Cell Lung Cancer: A Novel Immunoscore Approach

IntroductionImmune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non–small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. Materials and MethodsTissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. PD-L1 and PD-1 were evaluated by immunohistochemistry in the primary tumor and metastatic lymph node tissue. ResultsIn univariate analysis, a high density of PD-L1+ immune cells in the stromal compartment (S-PD-L1) and PD-1+ intraepithelial tumor infiltrating lymphocytes (T-PD-1) was associated with favorable disease-specific survival (DSS; S-PD-L1, P = .004; T-PD-1, P = .012), both limited to the squamous cell carcinoma histologic subgroup (S-PD-L1, P = .002; T-PD-1, P = .034). A combined low S-PD-L1 and T-PD-1 was associated with poor survival in all patients (DSS: hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.37-2.40; P < .001) at both centers and for all pathologic stages. In multivariate analysis, S-PD-L1 and T-PD-1 were independent positive prognostic factors, and combined low scores remained an independent prognosticator for poor survival (DSS: HR, 1.72; 95% CI, 1.29-2.28; P < .001; disease-free survival, P = .001; overall survival, P = .005). ConclusionOur study identified S-PD-L1 and T-PD-1 as independent positive prognostic factors for NSCLC patients. Their combination added significant prognostic impact within each pathologic stage and hence are feasible to include in a TNM Immunoscore.

Positive expression of protein chromosome 9 open reading frame 86 (C9orf86) correlated with poor prognosis in non-small cell lung cancer patients.

Chromosome 9 open reading frame 86 (C9orf86) is a novel subfamily of GTPases. Previous studies have implicated C9orf86 as a potential oncogene. C9orf86 expression was detected in non-small cell lung cancer (NSCLC) cell lines and human bronchial epithelial (16HBE) cell lines by RT-PCR and western blotting. Immunohistochemistry (IHC) was used to detect 180 consecutive NSCLC specimens and 16 normal lung tissues. The correlation between C9orf86 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox hazards ratio models were used to estimate the effect of C9orf86 expression on survival. C9orf86 was expressed in the cytoplasm in 74 of 180 (41.11%) NSCLC specimens. In clinical pathology analysis, C9orf86 expression significantly correlated with lymph node metastasis and clinical stage significantly (P<0.05). Multivariable analysis confirmed that C9orf86 expression increased the risk of death after adjusting for other clinicopathological factors (P<0.01). Overall survival (OS) and disease-free survival (DFS) were significantly prolonged in the C9orf86 negative group compared to the C9orf86 positive group (P<0.001). Adjuvant chemotherapy prolonged OS and DFS in resected NSCLC patients with C9orf86 negative expression (P<0.001) but not C9orf86 positive. Positive expression of C9orf86 is an independent prognostic factor for NSCLC patients, and C9orf86 may serve as a prognostic biomarker for patients with NSCLC.

RBX1 expression is an unfavorable prognostic factor in patients with non-small cell lung cancer

The purpose of this study was to assess the prognostic value of RBX1 in patients with non-small cell lung cancer (NSCLC). Quantitative real-time (RT-PCR) and western blot were used to evaluate the mRNA and protein expression of RBX1 in NSCLC and corresponding non-cancerous tissues. Immunohistochemistry was performed to examine the expression of RBX1 in 192 NSCLC tissue samples. Overall survival was evaluated by the Kaplan-Meier method and analyzed by the log-rank test between different groups. The results showed that the RBX1 expression was significantly higher in NSCLC tissues than the corresponding non-cancerous lung tissues. High RBX1 expression was related to poor tumor differentiation, advanced TNM stage, and lymph node metastasis. Patients with high RBX1 expression had poor overall survival than those with high expression levels, which was consistent with the results of the subgroup analysis. Multivariate analysis showed that high RBX1 expression was an unfavorable prognostic factor for NSCLC patients. Our study indicated that RBX1 might play an important role in the observation of prognosis in NSCLC and could be a valuable marker for predicting the treatment outcome in patients with NSCLC.

Prognostic significance of FDG PET/CT parameters in patients with non-small cell lung cancer of radiotherapy

Objective To investigate the metabolic parameters of primary lesions of non-small cell lung cancer (NSCLC) obtained by 18F-FDG PET/CT and their prognostic values in patients with NSCLC who underwent radiotherapy. Methods The clinical data of 170 NSCLC patients who underwent PET/CT scan before the first course of radiotherapy in Cancer Hospital, Chinese Academy of Medical Sciences, from January 2007 to December 2013 were analyzed retrospectively. The prognostic values of clinical factors, maximum standard uptake value (SUVmax) standard uptake value (SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were analyzed. The Kaplan-Meier method was applied for univariate survival analysis, the log-rank test was applied to compare the survival rate between groups, and the Cox proportional hazards regression was applied for multivariate survival analysis; P<0.05 was considered statistically significant. The number of patients who received the follow-up visit at 5 years were 48. Results The 5-year overall survival was 24.7%. The univariate analysis showed that age, N stage, clinical TNM stage, tumor size, SUVmax, MTV, and TLG were the prognostic factors in NSCLC patients who underwent radiotherapy (P=0.001-0.040). The Cox proportional hazards regression analysis of the above parameters showed that age and MTV of the primary lesion were the independent prognostic factors for overall survival (P=0.016, 0.005). Conclusions Age, N stage, clinical TNM stage, tumor size, SUVmax, MTV, and TLG are the prognostic factors in NSCLC patients undergoing radiotherapy, while age and MTV of the primary lesion are the independent prognostic factors. Key words: Lung neoplasms/radiotherapy; Tomography, positron-emission; Tomography, X-ray computed; Fluorodeoxyglucose; Prognosis

Prognostic value of serum CYFRA21-1 and CEA for non-small-cell lung cancer.

The aim of the study was to assess the clinical prognostic value of serum cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) for non-small-cell lung cancer (NSCLC) patients. Literatures related to effects of serum CYFRA21-1 and CEA on the prognosis of lung cancer patients were retrieved from databases such as PubMed, Springer Link, Embase, Wanfang, and CNKI. Meta-analysis was carried out using RevMan 5.1 software. Ten literatures involving 1990 NSCLC patients were selected in this study. Total survive estimation merging hazard ratio (HR) in all NSCLC patients with high-level serum CYFRA21-1 was 1.64 (95% CI 1.46–1.84, P < 0.001) and that in all NSCLC patients with high level serum CEA was 1.46 (95% CI 1.28–1.65, P < 0.001). Serum CYFRA21-1 and CEA can be used as prognostic factors of NSCLC patients. Combinative detection of the two indices will be more reliable.

MiR-32 functions as a tumor suppressor and directly targets SOX9 in human non-small cell lung cancer

PurposeMicroRNA-32 (miR-32) is dysregulated in certain human malignancies and correlates with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Thus, the aim of this study was to explore the effects of miR-32 expression on NSCLC tumorigenesis and development.MethodsUsing real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), we detected miR-32 expression in NSCLC cell lines and primary tumor tissues. The association of miR-32 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-32 expression on the biological behavior of NSCLC cells were investigated. Finally, the potential regulatory effect of miR-32 on SOX9 expression was confirmed.ResultsmiR-32 expression levels were significantly downregulated in NSCLC compared with the corresponding noncancerous lung tissues (P<0.001). In addition, decreased miR-32 expression was significantly associated with lymph node metastasis (P=0.002), advanced tumor/nodes/metastasis (TNM) classification stages (P<0.001), and shorter overall survival (P<0.001). Multivariate regression analysis corroborated that downregulated miR-32 expression was an independent unfavorable prognostic factor for NSCLC patients. In vitro studies demonstrated that miR-32 overexpression reduced A549 cell proliferation, migration, and invasion, and promoted apoptosis. Furthermore, SOX9 was confirmed as a direct target of miR-32, using a luciferase reporter assay.ConclusionThese findings indicate that miR-32 may act as a tumor suppressor in NSCLC and could serve as a novel therapeutic agent for miR-based therapy.

Treatment and prognostic analysis of patients with leptomeningeal metastases from non-small cell lung cancer.

BackgroundLeptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) are associated with poor prognosis and optimal treatment for this subgroup of NSCLC patients is controversial. The purpose of this study is to evaluate treatment options and prognostic factors of NSCLC patients with LM.MethodsWe retrospectively analyzed data of 108 patients who had been diagnosed with LM from NSCLC between May 2006 and August 2013.ResultsThe median survival time (MST) of the 108 patients was 5.3 months, and the one-year survival rate was 23.7%. Forty-nine patients received whole brain radiotherapy (WBRT) and the MST of patients who received WBRT and those who did not were 6.4 and 4.3 months, respectively. Forty-two patients were treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) after being diagnosed with LM. These patients had prolonged survival (11.1 vs. 4.4 months). Patients who received concomitant WBRT and EGFR-TKIs had the longest MST (12.3 months). Eastern Cooperative Oncology Group performance status, whether patients received WBRT, and/or EGFR-TKIs were independent prognostic factors for patients with LM from NSCLC.ConclusionWBRT, EGFR-TKIs or combined therapy, could lead to better clinical outcomes for NSCLC patients with LM. EGFR-TKIs plus WBRT has the potential to be the standard strategy for LM in NSCLC patients.

Effects of Rad51 on survival of A549 cells.

Rad51, a key factor in the homologous recombination pathway for the DNA double-strand break repair, plays a vital role in genesis of non-small-cell lung cancer (NSCLC). In recent years, more and more studies indicate that high expression of Rad51 is of great relevance to resistance of NSCLC to chemotherapeutic agents and ionizing radiation. However, the underlying molecular mechanisms are poorly understood. In this study, we investigated the role of single Rad51 on cell viability in vitro. Our results show that depletion of endogenous Rad51 is sufficient to inhibit the growth of the A549 lung cancer cell line, by accumulating cells in G1 phase and inducing cell death. We conclude that independent Rad51 expression is critical to the survival of A549 cells and can be an independent prognostic factor in NSCLC patients.

A Study Design: Concurrent EGFR-TKI and Thoracic Radiotherapy as Firstline Treatment of Stage IV NSCLC Patients with EGFR Active Mutations (CERTAIN Study)

Lung cancer is a common malignant tumor with high morbidity and mortality worldwide; more than 70 percent of patients are diagnosed with advanced disease. Nowadays, chemotherapy with concurrent thoracic radiotherapy (TRT) has been proven effective in stage IV NSCLC. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), such as gefitinib and erlotinib, is the standard first-line treatment for stage IV non-small cell lung cancer (NSCLC) patients harboring EGFR active mutations. Previous in vitro studies showed that EGFR-TKI could sensitize tumor cells to radiation, and some researches indicated that EGFR mutations appear to be favorable predictive and prognostic factors in NSCLC patients treated with radiotherapy. A retrospective study has indicated that the combination of EGFR-TKI with TRT as the first-line treatment for advanced NSCLC was effective. However, the efficacy of this novel combination treatment strategy needs to be further confirmed in a prospective study. This is an open-labeled, single-arm, phase II clinical trial aiming to evaluate the efficacy and safety of EGFR-TKI combined with thoracic radiotherapy as first-line treatment of stage IV NSCLC patients with positive EGFR mutations. We plan to enroll 47 patients not receiving therapy for primary and metastatic disease previously and with cytologically or pathologically confirmed stage IV NSCLC harboring EGFR active mutations. Each patient will receive erlotinib 150 mg per day orally with concurrent TRT (54~60 Gy/27~30 F/5.5~6 w, within 2 weeks from the beginning of enrollment) until disease progression or intolerable toxicities. The study has been initiated since January 2015 and will be finished in December 2017 expectedly.

MicroRNA-137 functions as a tumor suppressor in human non-small cell lung cancer by targeting SLC22A18

Our previous study demonstrated that the overexpression of solute carrier family 22 member 18 (SLC22A18) in human non-small cell lung cancer (NSCLC) tissues might be associated with tumor progression and patients’ prognosis. The aim of this study was to investigate the molecular mechanisms underlying its roles in NSCLC. As a result, bioinformatics analysis and luciferase reporter assay showed that microRNA (miRNA)-137 directly targeted SLC22A18 in NSCLC cells. Then, functional studies indicated that the ectopic expression of miR-137 significantly inhibited NSCLC cell proliferation, invasion and migration by targeting SLC22A18. More importantly, the decreased expression of miR-137 in clinical NSCLC tissues was correlated with advanced TNM stage, positive metastasis and poor prognosis of patients with this malignancy. In conclusion, these findings offer the convincing evidence that the roles of SLC22A18 in NSCLC progression may be partially caused by the regulatory effects of miR-137, which may function as a tumor suppressor. Our clinical data further indicated that miR-137 may be an independent favorable prognostic factor in NSCLC patients.

Elevated plasma interleukin-35 levels predict poor prognosis in patients with non-small cell lung cancer.

Interleukin-35 (IL-35) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of plasma IL-35 in patients with non-small cell lung cancer (NSCLC). Plasma collected from 106 patients with NSCLC cases and 78 healthy controls (HC) were subjected to IL-35 enzyme-linked immunosorbent assay (ELISA) and relationships between plasma IL-35 levels and clinical characteristics were evaluated. The correlation of IL-35 and overall survival was analyzed using Kaplan-Meier method. The prognostic value of IL-35 was tested using univariate and multivariate analysis. Circulating IL-35 levels were significantly higher in the NSCLC group in comparison with the HC group (21.37 ± 11.55pg/ml vs. 10.09 ± 5.32pg/ml, p < 0.001). Correlation analysis by subgroup indicated that plasma IL-35 correlated positively with tumor TNM stage (p < 0.001) and lymph node metastases (p < 0.0001). Using a cutoff level of 20.26pg/ml (median value), IL-35 showed an inverse correlation with overall survival. Univariate and multivariate analysis indicated that plasma IL-35 was an independent prognostic factor for NSCLC patients. Circulating IL-35 in NSCLC patients significantly increased. IL-35 is a promising potential biomarker in prognostication of clinical outcome of NSCLC patients and the regulation of IL-35 expression may provide a new target for the treatment of NSCLC patients.

Prognostic significance of combined pulmonary fibrosis and emphysema in patients with resected non-small-cell lung cancer: a retrospective cohort study.

Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder that is usually diagnosed on the basis of high resolution computed tomography (HRCT) findings. It is unclear whether CPFE is an independent prognostic factor in patients with non-small-cell lung cancer (NSCLC). Therefore, we conducted a retrospective analysis to assess the impact of CPFE on the prognosis of patients with completely resected NSCLC. We retrospectively reviewed 365 patients diagnosed with NSCLC who underwent complete resection at the Tazuke Kofukai Medical Research Institute, Kitano Hospital between January 2007 and December 2012. Patients were classified into four groups according to chest HRCT findings: those with CPFE, those with fibrosis, those with emphysema or those with a normal lung except for the presence of a tumour. We evaluated disease-free survival (DFS) and overall survival (OS) using the two-tailed log-rank test and the Cox proportional hazards model. The two-tailed log-rank test demonstrated that the four groups had significantly different DFS and OS (P < 0.01). In the multivariate analysis, CPFE was found to be an independent prognostic factor for DFS and OS compared with a normal lung [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.24-5.13; P = 0.01 and HR: 4.53; 95% CI: 1.91-10.7; P < 0.01, respectively]. CPFE is a significant, unfavourable prognostic factor for NSCLC patients after curative resection.

Prognostic factors for brain metastases from non-small cell lung cancer with EGFR mutation: influence of stable extracranial disease and erlotinib therapy.

The aim of this study was to explore prognostic factors for non-small cell lung cancer (NSCLC) patients with brain metastases (BM) on the basis of EGFR mutation status. Among 779 consecutive NSCLC patients who underwent EGFR mutation screening, all 197 patients with BM were divided according to the EGFR mutation status. The prognostic factors, including patient characteristics at the time of BM diagnosis, treatment history, and radiologic features, were analyzed. Of 197 patients with BM, 108 had wild-type EGFR and 89 had EGFR mutation. The patients with EGFR mutation presented longer overall survival after BM diagnosis (OS) than those with wild-type EGFR, regardless of whether BM was synchronous or metachronous. For the patients with EGFR mutation, favorable prognostic factors in multivariate analysis were age<65 (p=0.037), good performance status (PS) (p<0.0001), cranial radiotherapy (p=0.020), previous chemotherapy≤1 regimen (p=0.009), stable extracranial disease at BM diagnosis (p=0.022), and erlotinib therapy after BM diagnosis (p=0.0015). On the other hand, favorable prognostic factors for the patients with wild-type EGFR were only good PS (p=0.0037) and cranial radiotherapy (p=0.0005). Among patients treated with erlotinib after BM diagnosis, the patients with exon 19 deletion showed longer OS than those with exon 21 point mutation (p=0.019). The prognostic factors for NSCLC patients with BM were different according to the EGFR mutation status. Particularly in NSCLC patients with EGFR mutation and stable extracranial disease, regular cranial evaluation for detecting asymptomatic BM would lead to good prognosis. In addition, erlotinib therapy would be preferable in NSCLC patients with BM and EGFR mutation, especially those with exon 19 deletion.

The expression levels and prognostic value of high temperature required A2 (HtrA2) in NSCLC

High temperature required A2 (HtrA2) is a serine kinase that is released from mitochondria into the cytosol upon apoptotic stimuli, inducing apoptosis in various cancers. Thus, analysis of the expression of HtrA2 in non-small-cell lung cancer (NSCLC) tissues is needed for the understanding of this malignancy. In this study we firstly analyzed the apoptosis effect of HtrA2 in A549 cells by RNA interference and cisplatin with Western blot and flow cytometry. Then HtrA2 expression was evaluated by Western blot and immunohistochemistry in NSCLC tissues. Western blot and flow cytometry analyses indicated that deletion of HtrA2 was negatively correlated with apoptosis-induced protein in A549 cells. HtrA2 was lowly expressed in NSCLC and significantly associated with histological differentiation and clinical stage. Besides, low expression of HtrA2 was a prognostic factor for NSCLC patients’ inferior survival. In conclusion, HtrA2 might promote the apoptosis of NSCLC cells, and serve as a target for NSCLC's treatment.

Expression of WASF3 in patients with non-small cell lung cancer: Correlation with clinicopathological features and prognosis

Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis in different cancer cell types, and has been demonstrated to possess prognostic value in various types of human cancer. However, to the best of our knowledge, the expression profile of WASF3 and its correlations with the clinicopathological features of non-small cell lung cancer (NSCLC) have not yet been described. In the present study, the mRNA expression levels of WASF3, in 38 NSCLC patients and in matched normal tissues, were assessed using quantitative polymerase chain reaction and the protein expression in 96 specimens was analyzed using immunohistochemistry. In addition, patient survival data were collected retrospectively and the association between WASF3 expression and five-year overall survival was evaluated. The results demonstrated that the mRNA expression level of WASF3 in cancer tissues was markedly (approximately five times) higher compared with that of the normal tissues. The WASF3 protein expression profile in NSCLC was consistent with the mRNA expression result, which also correlated with the histological subtype and tumor stage. Furthermore, patients with WASF3-positive expression were associated with a poorer prognosis compared with those exhibiting WASF3-negative expression, and the five-year survival rate was 20.8 and 46.5%, respectively (Kaplan-Meier; log-rank, P=0.004). In the multivariate analysis, which included other clinicopathological features, WASF3 emerged as an independent prognostic factor (relative risk, 0.463; 95% CI, 0.271–0.792). These results indicate that WASF3 may be critical in the pathogenesis of NSCLC, in addition to being a valuable prognostic factor for NSCLC patients. Further investigations are required to identify the efficacy of WASF3 as a potential therapeutic target for the treatment of NSCLC.

Differential Expression of miR-125a-5p and let-7e Predicts the Progression and Prognosis of Non-Small Cell Lung Cancer

Aberrant expression of various microRNAs (miRNA) has shown diagnostic and prognostic significance in non-small cell lung cancer (NSCLC). qRT-PCR analysis confirmed altered expression of miR-125a-5p, let-7e, miR-30a, miR-30e and miR-30e-3p in 70 paired tissue and serum samples from NSCLC patients. The reduced expression of miR-125a-5p, let-7e and miR-30e was strongly associated with NSCLC dedifferentiation. The lost expression of miR-125a-5p and let-7e was associated with shorter overall survival and let-7e was an independent prognostic factor for NSCLC patients. These five miRNA expressions should be further evaluated as biomarkers for the early detection and prognosis of NSCLC patients.

Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy: Meta-Analysis

Introduction:The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect.Methods:We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy.Results:Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively.Conclusion:Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC.

Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T lymphocytes mixed effector cells: retrospective clinical observation.

The objective of the current study was to retrospectively investigate the efficacy of adaptive transfer of natural killer (NK) and cytotoxic T lymphocytes mixed effector (NKTm) cells in non-small cell lung cancer (NSCLC) patients in comparison to a control group of NSCLC patients. NKTm cells were obtained by ex vivo expansion of peripheral blood mononuclear cells (PBMCs) of patients followed with phenotype determination. Primary end point was overall survival (OS). Ex vivo expansion caused significant enrichment of CD3(+), CD3(+)CD8(+), CD45RO(+), CD25(+), CD29(+) and CD3(+)CD16(+)/CD56(+) cells (P<0.05). The OS of the immunotherapy group was significantly longer than that of the control group and the risk of death decreased by 43.8% (31.1 months vs 18.1 months, P=0.008, HR=0.562, 95% CI 0.367-0.860). Two-year survival rate of patients in the immunotherapy group was better than in the control group (62.95% vs 35.44%, P<0.05). Gender, clinical stage, application of TKI, number of chemotherapy cycle, and application of NKTm immunotherapy were independent prognostic factors for NSCLC patients. The OS in subgroups of males, <60 years age, clinical stage IIIb+IV, no brain metastases, without radiotherapy, chemotherapy of >6 cycles, no application of TKI and TKI invalid was prolonged after NKTm cellular immunotherapy (P<0.05). Ex vivo expansion of NKTm cells was effective and had no adverse safety concerns, thus highlight that adaptive transfer of NKTm cells may prolong the OS of NSCLC patients and increase 2 year survival rate.