Prognostic Factor In Non-small Cell Lung Cancer Research Articles

Clinicopathologic and prognostic implications of HOXA gene and its associated long-noncoding RNAs expression in non-small cell carcinoma: A meta-analysis.

We conducted an investigation into the correlation between HOXA and associated long-noncoding RNAs, along with their clinicopathologic and prognostic features in non-small cell lung cancer (NSCLC). A comprehensive search across multiple electronic databases, including PubMed and the Web of Science, was conducted to identify relevant studies. The association between HOXA, clinicopathologic parameters, and prognosis was assessed using relative risk (RR) and hazard ratio (HR) with a 95% confidence interval (CI). Data compilation was performed using STATA 12.0 software. A total of 11 trials involving 2058 patients with NSCLC were included in our study. Significant correlations were observed between HOXA-AS2 and TNM stage (III-IV) (RR=2.173, 95% CI: 1.386-5.437, P< 0.05) and HOTTIP and age (≥60-year-old) (RR=2.628, 95% CI: 1.185-5.829, P< 0.05) and non-smoking (RR=0.387, 95% CI: 0.156-0.959, P< 0.05). The combined results indicated a significant association between HOXA5 and increased overall survival (HR = 0.69, 95% CI = 0.57-0.84, P < .001). Additionally, HOXA-AS2, HOXA11 and HOTTIP were identified as potential independent predictors for poorer OS (HOXA-AS2: HR =3.48, 95% CI = 1.95 to 6.21, P < 0.05; HOXA11: HR=1.39, 95%CI = 1.08 to 1.79, P < 0.05; HOTTIP: HR=2.44, 95%CI = 1.10 to 5.42, P < 0.05). The prognostic significance of HOXA1, HOXA3 and HOXA4 was uncertain (HOXA1: HR=1.40, 95% CI =0.28 to 7.06, P > 0.05; HOXA3: HR=1.20, 95% CI = 0.96 to 1.50, P > 0.05; HOXA4: HR=0.97, 95% CI = 0.77 to 1.23, P > 0.05). The HOXA gene family has some potential to emerge as a novel prognostic factor for NSCLC and is correlated with some clinicopathological parameters such as the TNM stage, age and smoking. However, further meticulously designed prospective studies are warranted to substantiate these findings.

Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy

Anti-PD(L)-1 inhibition combined with platinum doublet chemotherapy (Chemo-IO) has become the most frequently used standard of care regimen in patients with non-small cell lung cancer (NSCLC). The negative impact of antibiotics on clinical outcomes prior to anti-PD(L)-1 inhibition monotherapy (IO) has been demonstrated in multiple studies, but the impact of antibiotic exposure prior to initiation of Chemo-IO is controversial. We assessed antibiotic exposures at two time windows: within 60 days prior to therapy (-60 d window) and within 60 days prior to therapy and 42 days after therapy (-60 + 42d window) in 2028 patients with advanced NSCLC treated with Chemo-IO and IO monotherapy focusing on objective response rate (ORR: rate of partial response and complete response), progression-free survival (PFS), and overall survival (OS). We also assessed impact of antibiotic exposure in an independent cohort of 53 patients. Univariable and multivariable analyses were conducted along with a meta-analysis from similar studies. For the -60 d window, in the Chemo-IO group (N = 769), 183 (24%) patients received antibiotics. Antibiotic exposure was associated with worse ORR (27% vs 40%, p = 0.001), shorter PFS (3.9 months vs. 5.9 months, hazard ratio [HR] 1.35, 95%CI 1.1,1.6, p = 0.0012), as well as shorter OS (10 months vs. 15 months, HR 1.50, 95%CI 1.2,1.8, p = 0.00014). After adjusting for known prognostic factors in NSCLC, antibiotic exposure was independently associated with worse PFS (HR 1.39, 95%CI 1.35,1.7, p = 0.002) and OS (HR 1.61, 95%CI 1.28,2.03, p < 0.001). Similar results were obtained in the -60 + 42d window, and also in an independent cohort. In a meta-analysis of patients with NSCLC treated with Chemo-IO (N = 4) or IO monotherapy (N = 13 studies) antibiotic exposure before treatment was associated with worse OS among all patients (n = 11,351) (HR 1.93, 95% CI 1.52, 2.45) and Chemo-IO-treated patients (n = 1201) (HR 1.54, 95% CI 1.28, 1.84). Thus, antibiotics exposure prior to Chemo-IO is common and associated with worse outcomes, even after adjusting for other factors. These results highlight the need to implement antibiotic stewardship in routine oncology practice.

Molecular alterations and clinical prognostic factors in resectable non-small cell lung cancer

BackgroundEGFR inhibitor and immunotherapy have been approved for adjuvant treatment in resectable non-small cell lung cancer (NSCLC). Limited reports of molecular and clinical characteristics as prognostic factors in NSCLC have been published.MethodsMedical records of patients with resectable NSCLC stage I–III diagnosed during 2015–2020 were reviewed. Real time-PCR (RT-PCR) was performed for EGFR mutations (EGFRm). Immunohistochemistry staining was conducted for ALK and PD-L1 expression. Categorical variables were compared using chi-square test and Fisher’s exact test. Survival analysis was done by cox-regression method.ResultsTotal 441 patients were included. The prevalence of EGFRm, ALK fusion, and PD-L1 expression were 57.8%, 1.9%, and 20.5% (SP263), respectively. The most common EGFRm were Del19 (43%) and L858R (41%). There was no significant difference of recurrence free survival (RFS) by EGFRm status whereas patients with PD-L1 expression (PD-L1 positive patients) had lower RFS compared to without PD-L1 expression (PD-L1 negative patients) (HR = 1.75, P = 0.036). Patients with both EGFRm and PD-L1 expression had worse RFS compared with EGFRm and PD-L1 negative patients (HR = 3.38, P = 0.001). Multivariable analysis showed higher CEA at cut-off 3.8 ng/ml, pT4, pN2, pStage II, and margin were significant poor prognostic factors for RFS in the overall population, which was similar to EGFRm population (exception of pT and pStage). Only pStage was a significant poor prognostic factor for PD-L1 positive patients. The predictive score for predicting of recurrence were 6 for all population (63% sensitivity and 86% specificity) and 5 for EGFRm population (62% sensitivity and 93% specificity).ConclusionThe prevalence and types of EGFRm were similar between early stage and advanced stage NSCLC. While lower prevalence of PD-L1 expression was found in early stage disease. Patients with both EGFRm and PD-L1 expression had poorer outcome. Thus PD-L1 expression would be one of the prognostic factor in EGFRm patients. Validation of the predictive score should be performed in a larger cohort.

Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis.

Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs). Several electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted. In this meta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09-2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64-1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1-2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0-1 and 2 vs. 1) showed similar results. LIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis.

Populations particulières : patients de performance status 2 ou plus: Special populations: patients with performance status 2 or higher

Performance status (PS) is a measure of the patient’s overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80 %, ECOG 2 = Karnofsky 60-70 %, ECOG 3-4 = Karnofsky 50-10 %. Numerous factors, whether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Preoperative computed tomography-based tumoral radiomic features prediction for overall survival in resectable non-small cell lung cancer.

The purpose of this study was to evaluate whether preoperative radiomics features could meliorate risk stratification for the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. After rigorous screening, the 208 NSCLC patients without any pre-operative adjuvant therapy were eventually enrolled. We segmented the 3D volume of interest (VOI) based on malignant lesion of computed tomography (CT) imaging and extracted 1542 radiomics features. Interclass correlation coefficients (ICC) and LASSO Cox regression analysis were utilized to perform feature selection and radiomics model building. In the model evaluation phase, we carried out stratified analysis, receiver operating characteristic (ROC) curve, concordance index (C-index), and decision curve analysis (DCA). In addition, integrating the clinicopathological trait and radiomics score, we developed a nomogram to predict the OS at 1 year, 2 years, and 3 years, respectively. Six radiomics features, including gradient_glcm_InverseVariance, logarithm_firstorder_Median, logarithm_firstorder_RobustMeanAbsoluteDeviation, square_gldm_LargeDependenceEmphasis, wavelet_HLL_firstorder_Kurtosis, and wavelet_LLL_firstorder_Maximum, were selected to construct the radiomics signature, whose areas under the curve (AUCs) for 3-year prediction reached 0.857 in the training set (n=146) and 0.871 in the testing set (n=62). The results of multivariate analysis revealed that the radiomics score, radiological sign, and N stage were independent prognostic factors in NSCLC. Moreover, compared with clinical factors and the separate radiomics model, the established nomogram exhibited a better performance in predicting 3-year OS. Our radiomics model may provide a promising non-invasive approach for preoperative risk stratification and personalized postoperative surveillance for resectable NSCLC patients.

Prognostic value of pretherapeutic FDG PET/CT in non-small cell lung cancer with pulmonary lymphangitic carcinomatosis

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.

Populations particulières : patients de Performance Status 2 ou plus

Performance status (PS) is a measure of the patient’s overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80%, ECOG 2 = Karnofsky 60-70%, ECOG 3-4 = Karnofsky 50-10%. Numerous factors, whether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer.

Lung cancer remains a leading cause of cancer-related deaths worldwide, overtaking colon, breast, and prostate cancer-related deaths. Due to the limited diagnostic possibilities, it is often diagnosed after it has reached an advanced stage. The delayed diagnosis significantly worsens the patient’s prognosis. In recent years, we have observed an increased interest in the use of microRNAs (miRNAs) as diagnostic, predictive, and prognostic markers in non-small-cell lung cancer (NSCLC). The abnormal expression levels of the miRNAs could be used to detect NSCLC in its early stages while it is still asymptomatic. This could drastically improve the clinical outcome. Furthermore, some miRNAs could serve as promising predictive and prognostic factors for NSCLC. Some of the currently available studies have shown a correlation between the miRNAs’ levels and the sensitivity of tumour cells to different treatment regimens. Analysing and modulating the miRNAs’ expression could be a way to predict and improve the treatment’s outcome.

Long non-coding MELTF Antisense RNA 1 promotes and prognosis the progression of non-small cell lung cancer by targeting miR-1299

ABSTRACT This paper explored the influence of long non-coding MELTF Antisense RNA 1 (lncRNA MELTF-AS1) on the prognosis of non-small cell lung cancer (NSCLC), and further deepened the understanding of NSCLC. A total of 130 patients with NSCLC participated in current study to detect and compare lncRNA MELTF-AS1 expression in cancer and normal tissues. Kaplan-Meier analysis and log-rank test were chosen to analyze the effect of MELTF-AS1 expression on the survival of patients within 5 years. The correlation between the expression of MELTF-AS1 and the clinical characteristics of NSCLC patients was analyzed, and the prognostic factors of NSCLC were analyzed by multivariate Cox regression. Subsequently, MELTF-AS1 expression in NSCLC cells were detected. The Cell Counting Kit-8 (CCK-8) and Transwell methods were selected to study the proliferation, migration capability and invasion level of NSCLC cells that silencing MELTF-AS1. Through the luciferase activity assay to explore the relationship between MELTF-AS1 and miR-1299, to further understand the effect of silencing MELTF-AS1 on NSCLC. MELTF-AS1 was increased in NSCLC tissues and cells. Silencing MELTF-AS1 suppressed the proliferation ability, migration capability and invasion level of NSCLC cells, which means that low expression of MELTF-AS1 may be more conducive to patient survival. In addition, through luciferase activity analysis and bioinformatics analysis, MELTF-AS1 has a negative effect on miR-1299, and silencing MELTF-AS1 enhanced miR-1299 expression in NSCLC cells. MELTF-AS1 is highly likely to be a promising prognostic biomarker, and associated with the progression of NSCLC.

Interferon regulatory factor-1 regulates cisplatin-induced apoptosis and autophagy in A549 lung cancer cells

This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase 3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase 3 activity were evaluated using commercial kits. Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment-induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer.

POSA177 Real-World Profiling of Non-Small Cell Lung Cancer Patients in Japan

Lung cancer is the leading cause of cancer-related mortality in Japan, with non-small cell lung cancer (NSCLC) accounting for ∼85%. There is a paucity of research in Japan on clinical characteristics, treatment outcomes and prognostic factors of NSCLC. This real-world study aimed to understand patient characteristics and treatment strategies for NSCLC management in Japan.

Pretreatment Albumin-to-Alkaline Phosphatase Ratio Is a Prognostic Marker in Lung Cancer Patients: A Registry-Based Study of 7077 Lung Cancer Patients.

Simple SummarySince the albumin-to-alkaline phosphatase ratio (AAPR) has shown promising prognostic prediction in cancer patients, the prognostic value of the AAPR was evaluated in a large cohort of 7077 lung cancer patients. We combined patient data from the Danish Lung Cancer Registry and the clinical laboratory information system (LABKA) and showed that a low AAPR was independently associated with an inferior median overall survival in non-small cell lung cancer patients and small cell lung cancer patients. Furthermore, data indicated a level-dependent correlation between the AAPR and survival and that the AAPR added additional prognostic value to the already well-established prognostic markers in lung cancer. Therefore, if our findings are validated in the future, the AAPR should be incorporated as a factor in the general prognostication of lung cancer patients.The albumin-to-alkaline phosphatase ratio (AAPR) is a novel promising prognostic marker in cancer patients. However, the evidence for its significance in lung cancer is scarce. Therefore, we assessed the prognostic value of the AAPR in a large cohort of lung cancer patients. Data on lung cancer patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and combined with data on the pretreatment serum AAPR level extracted from the clinical laboratory information system (LABKA). AAPR tertiles were applied as cutoffs. Cox proportional hazard models assessed the prognostic value of the AAPR. In total, 5978 non-small cell lung cancer (NSCLC) patients and 1099 small cell lung cancer (SCLC) patients were included. Decreasing AAPR level was significantly associated with declining median overall survival (OS) in NSCLC patients (medium vs. low AAPR, adjusted HR = 0.73 (95% confidence interval (CI) 0.68–0.79); high vs. low AAPR, adjusted HR = 0.68 (95% CI 0.62–0.73)) and in SCLC patients (medium vs. low AAPR, adjusted HR = 0.62 (95% CI 0.52–0.74); high vs. low, adjusted HR = 0.59 (95% CI 0.50–0.70)). In conclusion, the AAPR was an independent prognostic factor in NSCLC and SCLC patients. The correlation seems to be level dependent, with reducing survival found to be associated with decreasing AAPR level.

STAT3/miR-135b/NF-\u03baB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is one of the most commonly diagnosed cancers worldwide but has limited effective therapies. Uncovering the underlying pathological and molecular changes, as well as mechanisms, will improve the treatment. Dysregulated microRNAs (miRNAs) have been proven to play important roles in the initiation and progression of various cancers, including NSCLC. In this manuscript, we identified microRNA-135b (miR-135b) as a tumor-promoting miRNA in NSCLC. We found that miR-135b was significantly upregulated and that its upregulation was associated with poor prognosis in NSCLC patients. miR-135b was an independent prognostic factor in NSCLC. Overexpressing miR-135b significantly promoted the aggressiveness of NSCLC, as evidenced by enhanced cell proliferation, migration, invasion, anti-apoptosis, and angiogenesis in vitro and in vivo, and knockdown of miR-135b had the opposite effects. Mechanistically, our results reveal that miR-135b directly targets the 3′-untranslated region (UTR) of the deubiquitinase CYLD, thereby modulating ubiquitination and activation of NF-κB signaling. Moreover, we found that interleukin-6 (IL-6)/STAT3 could elevate miR-135b levels and that STAT3 directly bound the promoter of miR-135b; thus, these findings highlight a new positive feedback loop of the IL-6/STAT3/miR-135b/NF-κB signaling in NSCLC and suggest that miR-135b could be a potential therapeutic target for NSCLC.

Evaluation of the Effect of Lymph Node Status on the Survival of Non-Small Cell Lung Cancer Patients With Brain Metastases: Applications of a Novel Grade Prognostic Assessment Score Model Involving N Stage.

BackgroundGrade prognostic assessment (GPA) is widely used to evaluate the prognosis of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This study aimed to investigate whether lymph node status (LNS) could be included as one of the GPA variables for NSCLC with BMs.MethodsOverall, 586 patients with NSCLC and BMs were retrospectively analyzed. Overall survival stratified by LNS was analyzed using the Kaplan-Meier method. Multivariate analysis was also performed to identify independent prognostic factors using the Cox proportional hazards progression model. In the updated GPA index, prognostic factors and criteria of GPA score were weighted by effect magnitude relative risk (RR) and statistical significance.ResultsIn NSCLC patients with BMs, those with lymph node involvement had worse overall survival (mOS, 13.4 months vs. 25.9 months, P <0.001) than those without lymph node involvement. Multivariate analysis showed that LNS might be an independent prognostic factor (RR: 1.702, CI: 1.340–2.162, P <0.001). Finally, five prognostic factors including LNS, the age of the patient, Karnofsky performance status (KPS), the number of BMs, and extracranial metastases were enrolled in our novel GPA index. With the updated GPA index involving the N stage, survival analysis was also performed. Prognostic results were significantly different among these four subgroups (Class A vs. Class B, P=0.047; Class B vs. Class C, P<0.001; Class C vs. Class D, P=0.007).ConclusionsThese results indicate that LNS might be an indispensable prognostic factor in NSCLC with BM. The novel GPA model involving the N stage could provide more reliable evidence to estimate the survival of NSCLC patients with BMs.

Prognostic and clinicopathological significance of long noncoding RNA MALAT-1 expression in patients with non-small cell lung cancer: A meta-analysis.

Although expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in tumor tissues has been assessed in several malignancies. However, the association between lncRNA MALAT-1 expression and prognosis or clinicopathological feature remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA MALAT-1 expression was associated with prognosis or clinicopathological features in patients with non-small cell lung cancer (NSCLC). We searched Embase, PubMed, Web of Science, Cochrane library, The Chinese National Knowledge Infrastructure, and Wanfang databases from inception to March, 1, 2020. The language restrictions were Chinese and English. The published literature on lncRNA MALAT-l expression and prognosis or clinicopathological characteristics of NSCLC patients was statistically analyzed. Combined hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were used to evaluate the effects of lncRNA MALAT-l on the prognosis and clinicopathological features of NSCLC. Fifteen studies with 1477 NSCLC patients were enrolled. The results showed that the elevated expression of lncRNA MALAT-l in tumor tissues was associated with shorter overall survival (OS) (HR: 2.20, 95% CI: 1.53-3.16; P = 0.000). Additionally, high lncRNA MALAT-l expression was also significantly associated with gender (OR: 0.69, 95% CI: 0.51-0.93; P = 0.014), tumor size (OR: 1.87, 95% CI:1.13-3.09; P = 0.016), lymph node metastasis (LNM) (OR: 2.87, 95% CI:1.05-7.83, P = 0.04), tumor differentiation (OR: 1.60, 95% CI:1.17-2.20; P = 0.003), and tumor-node-metastasis (TNM) stage (OR: 0.42, 95% CI: 0.25-0.70; P = 0.001). There was no significant relationship between lncRNA MALAT-l expression and other clinicopathological features including age (OR: 1.03, 95% CI: 0.79-1.34; P = 0.830), number of tumors (OR: 1.02, 95% CI: 0.63-1.64; P = 0.943), vascular invasion (OR: 1.23, 95% CI: 0.50-3.05; P = 0.652), and recurrence (OR: 1.98, 95% CI: 0.67-5.85; P = 0.214). The overexpression of lncRNA MALAT-l in NSCLC tissues was correlated with OS, gender, tumor size, LNM, tumor differentiation, and TNM stage. Thus, lncRNA MALAT-l may serve as a prognostic factor for NSCLC.

MiR-1225-5p inhibits non-small cell lung cancer cell proliferation, migration and invasion, and may be a prognostic biomarker.

Non-small cell lung cancer (NSCLC) is a malignant tumor, which presents with a high 5-year mortality rate owing to the lack of an effective early screening tool and the absence of obvious early symptoms. MicroRNAs (miRs/miRNAs) have attracted increasing attention due to their significant clinical value in the diagnosis and prognosis of various human malignancies. The present study aimed to investigate the expression levels of microRNA (miR)-1225-5p in NSCLC and to analyze its prognostic value and biological role. The expression levels of miR-1225-5p in the tissues of patients with NSCLC and NSCLC cell lines were analyzed using reverse transcription-quantitative PCR. The association between miR-1225-5p expression levels and the clinicopathological features of patients with NSCLC was analyzed using a χ2 test. The prognostic value of miR-1225-5p in NSCLC was analyzed using both Kaplan Meier survival and Cox regression analyses, and the effects of miR-1225-5p on NSCLC cell proliferation, migration and invasion were examined. The results revealed that the expression levels of miR-1225-5p were significantly downregulated in NSCLC tissues compared with normal control tissues. Furthermore, miR-1225-5p was discovered to be a potential independent prognostic factor in NSCLC. The inhibition of miR-1225-5p in NSCLC cell lines led to increased cell proliferation, migration and invasion, whereas miR-1225-5p overexpression exerted the opposite effects in these cells. In conclusion, the findings of the present study indicated that the downregulated expression levels of miR-1225-5p in NSCLC may predict a poor prognosis in patients and suggested miR-1225-5p as a potential therapeutic target for NSCLC.

Expression of PD-L1, cancer stem cell and epithelial–mesenchymal transition phenotype in non-small cell lung cancer

The purpose of this study was to investigate the expression of PD-L1, cancer stem cells (CSC) markers (CD44, NANOG, and ALDH1) and epithelial-mesenchymal transition (EMT) markers and to evaluate their correlation and prognostic significance in non-small cell lung cancer (NSCLC) patients. PD-L1 protein expression was evaluated in resected 277 NSCLC cases and its correlation with CSC and EMT marker expression and survival was determined based on immunohistochemical (IHC) analysis. mRNA expression obtained from The Cancer Genome Atlas and the Kaplan-Meier plotter database were compared with the IHC results. PD-L1 expression was negatively correlated with ALDH1 expression in adenocarcinoma by IHC and mRNA expression. PD-L1 expression was also associated with mesenchymal phenotype (vimentin and TWIST) adenocarcinoma by IHC and mRNA expression. PD-L1 expression was associated with poor prognosis in adenocarcinoma by IHC. However, NANOG or ALDH1 expression measured by IHC and mRNA expression was correlated with a favourable prognosis in adenocarcinoma. Epithelial marker p120-catenin detected by IHC and mRNA expression was associated with a favourable prognosis in adenocarcinoma, however mesenchymal marker TWIST was associated with a worse prognosis. Patients with low PD-L1 and high ALDH1 expression showed more favourable prognoses than adenocarcinoma patients with other expression patterns. In multivariate analysis, ALDH1 detected by IHC and mRNA expression was an independent favourable prognostic marker for adenocarcinoma. Our study results support the hypothesis that PD-L1 interacts with CSC and EMT features and that PD-L1, ALDH1, and the mesenchymal phenotype may serve as tandem markers as prognostic factor in NSCLC.

Populations particulières : patients de Performance Status 2 ou plus: Special Populations: Patients with Performance Status 2 or higher

AbstractPerformance status (PS) is a measure of the patient’s overall condition. Karnofsky and ECOG (Eastern Cooperative Oncology Group) are the most widely used scales. A three-point conversion scale allows a strong correlation between both scores: ECOG 0-1 = Karnofsky 100-80 %, ECOG 2 = Karnofsky 60-70 %, ECOG 3-4 = Karnofsky 50-10 %. Numerous factors, wether linked to cancer or to comorbidities, can affect PS. PS remains a major independent prognostic factor in NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer), despite its flawed reproducibility and the heterogeneity of cancer patients with poor PS. As a matter of fact, PS should be regarded as a stratification factor in research. All guidelines take PS into account as a therapeutic decision making tool, especially in the case of chemotherapy for metastatic NSCLC. Targeted therapy should be considered in case of metastatic disease with molecular targets regardless of PS, for its high effectiveness and good safety profile. Data regarding immunotherapy are rather sketchy. Tolerance seems to be fine. Findings regarding efficacy warrant careful selection of patients who might benefit from this therapy. In light of the European Medicines Agency call, let us build studies dedicated to patients as frail as they come and enroll them in clinical trials in such a way that they benefit, among others, from therapeutic advances. In order to apply clinical research findings to the general population, specific groups of patients should be more involved.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.