Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome

The immunoproteasome plays a key role in generation of HLA peptides for T cell-mediated immunity. Integrative genomic and proteomic analysis of non-small cell lung carcinoma (NSCLC) cell lines revealed significantly reduced expression of immunoproteasome components and their regulators associated with epithelial to mesenchymal transition. Low expression of immunoproteasome subunits in early stage NSCLC patients was associated with recurrence and metastasis. Depleted repertoire of HLA class I-bound peptides in mesenchymal cells deficient in immunoproteasome components was restored with either IFNγ or 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Our findings point to a mechanism of immune evasion of cells with a mesenchymal phenotype and suggest a strategy to overcome immune evasion through induction of the immunoproteasome to increase the cellular repertoire of HLA class I-bound peptides.Proteasomes are multisubunit complexes that degrade intracellular proteins through the ubiquitin–proteasome pathway (1). The three catalytic β subunits β1, β2, and β5 in the proteasome complex are replaced by proteasome (prosome, macropain) subunit B9 (PSMB9)/β1i, PSMB10/β2i, and PSMB8/β5i, respectively, to form the immunoproteasome (2). The immunoproteasome generates peptides suitable for binding onto HLA I molecules, facilitating antigen presentation for CD8⁺ T-cell responses. Lack of expression or down-regulation of the immunoproteasome may contribute to immune evasion through antigen loss (3).The impact of immunoproteasome expression on antigen presentation in tumors of epithelial origin is not well established. We have investigated the constitutive and induced expression patterns of immunoproteasome subunits in non-small cell lung carcinoma (NSCLC) and their impact on antigen presentation. We provide evidence for dysregulated expression of immunoproteasome subunits in NSCLC cells with a mesenchymal phenotype, associated with a markedly reduced repertoire of HLA-bound peptides. Reduced expression of immunoproteasome subunits in NSCLC was also associated with reduced disease free survival.     

恩度与化疗联合治疗非小细胞肺癌疗效观察

目的探讨重组人血管内皮抑制素(恩度)联合化疗方案治疗非小细胞肺癌(NSCLC)的疗效与毒副反应。方法选择NSCLC患者58例,随机分为观察组与对照组各29例,观察组给予恩度联合常规化疗,对照组给予单纯常规化疗,比较两组患者治疗效果与毒副反应。结果所有患者均完成2个周期以上,两组患者近期疗效比较无统计学差异(P>0.05);观察组1年总生存率(58.6%)与1年内肿瘤无进展生存率(20.7%)均显著高于对照组(27.6%,3.4%)(P<0.05),随访至今,观察组肿瘤无进展生存期(PFS)显著高于对照组(P<0.01);两组毒副反应比较差异无统计学意义(P>0.05)。结论恩度联合化疗方案治疗NSCLC疗效显著且安全性高,且不增加毒副反应发生率。     

晚期非小细胞肺癌生存因素分析

目的探讨晚期非小细胞肺癌(NSCLC)患者的预后相关因素。方法回顾性分析106例晚期NSCLC患者的病例资料;Kaplan-M eier方法分析单因素对生存时间的影响;Log-rank法检验比较生存时间之间的差异;多因素分析采用Cox比例风险模型。结果单因素分析表明KPS评分、手术、体重减轻、临床分期、细胞分化、化疗方案及治疗前血小板(PLT)的水平与患者预后相关(P0.05)。多因素分析表明,KPS评分、PLT、临床分期及体重减轻是晚期NSCLC患者预后的独立影响因素(P0.05)。结论治疗前PLT水平、临床分期、KPS评分及体重减轻是晚期NSCLC患者预后的独立影响因素。     

miR-1290 is a potential prognostic biomarker in non-small cell lung cancer

Background

miR-1290 is a newly discovered microRNA (miRNA), and its role in non-small cell lung cancer (NSCLC) remains unknown. This study aimed to evaluate the expression levels of miR-1290 in NSCLC tissues and serum, and explore its associations with clinicopathological characteristics and prognosis of NSCLC patients.

Methods

A total of 33 pairs of tissues and 73 serum samples were obtained from NSCLC patients and expression levels of miR-1290 were detected by specific TaqMan qRT-PCR. The relationship between miR-1290 expression levels in NSCLC tissues and serum and clinicopathological characteristics was estimated respectively. The correlation between serum miR-1290 expression levels and overall survival of NSCLC patients was performed by Kaplan-Meier analysis and Cox proportional hazards model.

Results

We determined that miR-1290 expression levels were increased significantly in NSCLC tissues compared with non-tumor adjacent normal tissues, and higher miR-1290 expression levels were positively correlated with high tumor stage (P=0.004) and positive lymph node metastasis (P=0.013). Compared with benign lung disease and healthy controls, serum levels of NSCLC patients exhibited higher expression of miR-1290. Furthermore, the up-regulation of serum miR-1290 more frequently occurred in NSCLC patients with high TNM stage, positive lymph node metastasis (P=0.022 and P=0.024, respectively). Kaplan-Meier analysis demonstrated that high serum miR-1290 expression levels predicted poor survival (P=0.022). Cox proportional hazards risk analysis indicated that miR-1290 was an independent prognostic factor for NSCLC.

Conclusions

Our study suggests that miR-1290 is overexpressed in NSCLC, and serum miR-1290 may be used as a potential prognostic biomarker for NSCLC.     

Detection of occult tumor cells in regional lymph nodes is associated with poor survival in pN0 non-small cell lung cancer: a meta-analysis

Background

patients of pN₀ non-small cell lung cancer (NSCLC) with occult tumor cells (OTCs) in regional lymph nodes (LNs) are reported to have controversial prognostic outcomes.

Method

We pooled pN₀ NSCLC patients with OTCs in LNs and compared with those without OTCs. Patient characteristics, hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and/or disease-free survival (DFS) were analyzed. HR greater than 1 conferred an increased hazard for patients with OTCs.

Results

Eighteen articles were finally enrolled in the meta-analysis and 15 studies provided sufficient data for extracting HRs for OS, resulting to 5 articles available for DFS analysis. The combined HRs of OS was 2.22 (95% CI, 1.87 to 2.64) and 2.4 (95% CI, 1.71 to 3.36) for analysis of DFS. The similar trend was obtained in the subgroup analyses regarding detection methods and study type. Interestingly, even in the analysis of mean numbers of LNs dissection (MLND) intraoperatively, both subgroups (LNs/Pts. <12 and ≥12) illustrated significant HRs of OS (HR: 3.13, 95% CI, 2.17 to 4.52 in LNs/Pts. <12 subgroup and HR: 2.09, 95% CI, 1.63 to 2.68 in LNs/Pts. ≥12). The combined HR of OS in this section was 2.37 (95% CI, 1.63 to 2.68). No publication bias was detected in all the meta-analysis sections. The prognosis of patients with OTCs is inferior to those without OTCs in the terms of OS and DFS regardless of detection methods, study types and MLND.

Conclusions

The prognosis of patients with OTCs is inferior to those without OTCs in the terms of OS and DFS regardless of detection methods, study types and MLND.     

Factors associated with long-term survival of patients with advanced non-small cell lung cancer

Background and objective: Only a small proportion of patients with advanced non‐small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The aim of this study was to identify the factors associated with long‐term survival of patients with advanced NSCLC. Methods: Patients who had received chemotherapy for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied retrospectively. Data were gathered prospectively from a comprehensive database. Long‐term survivors (>2 years) were compared with the other patients, with respect to clinical, biological and tumour–node–metastasis criteria. Results: Data for 245 consecutive patients were collected. Thirty nine patients (15.9%) survived for more than 2 years. Long‐term survivors were more likely to have had metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01), a performance status (PS) of 0–1 at first progression of the tumour (P = 0.002), a tumour that was controlled with first (P < 0.0001) and second‐line (P = 0.004) chemotherapy, maintenance therapy (P = 0.001), curative surgery (P < 0.0001), time to first progression of the tumour of >3 months (P < 0.0001), normal LDH levels at diagnosis (P = 0.049), and a haemoglobin concentration >110 g/L at first progression of the tumour (P = 0.02). In multivariate analysis, surgery, maintenance treatment, time to first progression of the tumour of >3 months, a PS of 0–1 at first progression, the number of chemotherapy agents received, and LDH levels, were significant predictors of long‐term survival. Conclusions: Assessment of these factors, and the use of maintenance therapy, when possible, may identify a population of patients with NSCLC that is likely to have a prolonged life expectancy.     

Peripheral blood eosinophilia may be a prognostic biomarker in non-small cell lung cancer patients treated with immunotherapy

BackgroundEosinophils have been traditionally associated with the initiation and propagation of inflammatory responses, particularly in allergic diseases and helminth infections. More recently, an association between eosinophils and cancer has been the focus of several studies, but controversial results have emerged. This study aims to evaluate the prognostic role of peripheral blood eosinophilia in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We also evaluated the impact of peripheral eosinophilia on the occurrence of immune-related adverse effects (irAEs).MethodsAdvanced NSCLC patients under IO were included in a retrospective single-center study. Peripheral blood eosinophilia was defined by a count greater than 500/µL. Patients were analyzed for eosinophil counts, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR).ResultsA total of 121 NSCLC patients receiving IO were included. Thirty-three (27.3%) patients presented peripheral blood eosinophilia during treatment. Patients with peripheral eosinophilia presented more frequently non-progression as best overall response to IO (83.3% vs. 58.1%, P=0.014), higher median OS (26.6 vs. 9.5 months, P=0.022) and higher median PFS (13.8 vs. 4.6 months, P=0.013). IrAEs were more common in patients with peripheral eosinophilia (66.7% vs. 36.4%, P=0.003).ConclusionsThis study suggests that peripheral blood eosinophilia may predict better outcomes in NSCLC patients receiving IO, despite being associated with an increased risk of irAEs. According to our findings eosinophils may be involved in immune response against tumor. Routine eosinophils count assessment may be an additional prognostic tool in NSCLC patients receiving IO.     

Non-surgical therapy for patients with advanced non-small cell lung cancer

Abstract Non-small cell lung cancer is the major cancer problem in the Western World. Treatment and prognosis are highly stage dependent, although overall only 5–10% of patients will be alive 5 years after diagnosis. Patients with early stage disease are treated with surgery alone. However, for patients with locally advanced disease there is increasing evidence that combined modality approaches, incorporating chemotherapy, radiotherapy and/or surgery result in modest improvements in survival. For patients with metastatic non-small cell lung cancer there is evidence from metaanalyses and randomised studies that chemotherapy results in improvements in both duration and quality of life. Despite these advances, there is substantial room for further improvement and therefore, wherever possible, patients should be enrolled in well designed clinical studies.     

中性-淋巴比和预后营养指数与非小细胞肺癌患者预后的相关性研究

目的探讨中性粒细胞-淋巴细胞比率和预后营养指数与进展期非小细胞肺癌预后的相关性。方法回顾性分析安徽医科大学第一附属医院呼吸内科2010年1月至2013年1月确诊的Ⅲb期及Ⅳ期非小细胞肺癌患者109例,根据首次化疗前中性粒细胞-淋巴细胞比率及预后营养指数,分为低中性粒细胞-淋巴细胞比率组(2.97)和高中性粒细胞-淋巴细胞比率组(≥2.97),低预后营养指数组(45.95)和高预后营养指数组(≥45.95)。分析潜在的预后因素如中性粒细胞-淋巴细胞比率、预后营养指数、性别、年龄、组织类型、转移部位数、化疗次数、化疗方案等。结果多因素分析结果示:中性粒细胞-淋巴细胞比率(无进展生存期:P=0.015,总生存期:P=0.018),预后营养指数(无进展生存期:P=0.012,总生存期:P=0.006)、年龄(无进展生存期:P0.001,总生存期:P0.001)及化疗次数(无进展生存期:P0.001,总生存期:P0.001)是影响进展期非小细胞肺癌患者的独立预后因素,中性粒细胞-淋巴细胞比率≥2.97及预后营养指数45.95预示非小细胞肺癌患者无进展生存期或总生存期较短。结论中性粒细胞-淋巴细胞比率和预后营养指数均是预测进展期非小细胞肺癌患者预后的独立因素,高的中性粒细胞-淋巴细胞比率及低的预后营养指数与患者预后差相关。     

培美曲塞治疗晚期非小细胞肺癌近期疗效及毒性反应研究

目的研究多靶点叶酸拮抗剂培美曲塞治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒性反应。方法收集我院2008年1月至2010年1月资料完整的晚期非小细胞肺癌患者共18例,男10例,女8例,中位年龄51岁(范围32～68岁),均经组织学和/或细胞学证实,因化疗后出现复发或进展而采用培美曲塞化疗。化疗方案为培美曲塞500mg/m2单药或联合顺铂75mg/m2,每3周重复;对接受两个或两个以上化疗周期的患者进行化疗效果及副反应评价。结果 18例可评价疗效,无完全缓解(CR)病例,部分缓解(PR)仅2例,稳定者(SD)共12例,4例疾病进展(PD)。全组有效率(CR+PR)为11.1%(2/18),疾病控制率(DCR)为77.8%(14/18)。中位生存时间9.2个月,中位疾病进展时间2.8个月,1年生存率为31.2%。未出现化疗相关死亡,毒副反应主要为I～Ⅲ度胃肠道反应和骨髓抑制。结论培美曲塞治疗复治晚期NSCLC安全有效,耐受性良好。     

厄洛替尼与化疗治疗晚期非小细胞肺癌的临床观察

目的观察厄洛替尼与含铂化疗方案治疗晚期非小细胞肺癌的疗效和安全性。方法对我院晚期NSCLC给予化疗组30例,服用厄洛替尼组27例定期随访,观察疗效与不良反应。结果 57例可评价疗效的患者中,化疗组30例:CR:0例,PR:6例,SD:10例,PD:14例;缓解率6/30(20%),疾病控制率16/30(53.3%);服用厄洛替尼组27例:CR:2例,PR:8例,SD:14例,PD:3例;缓解率:10/27(37.1%),疾病控制率24/27(88.9%);不良反应主要表现在骨髓抑制、胃肠道反应以及皮疹,发生率在化疗组和厄洛替尼组分别为76.7%、80%、13.3%及3.71%、40.7%、66.7%,三者之间均有显著性差异。结论厄洛替尼治疗晚期NSCLC患者的疗效较化疗组好,且安全性高。     

Elevated pretreatment serum globulin albumin ratio predicts poor prognosis for advanced non-small cell lung cancer patients

Background

The aim of the present study was to explore the association between the pretreatment globulin albumin ratio (GAR) and the survival of advanced non-small cell lung cancer (NSCLC) patients.

Methods

Patients hospitalized between January 2007 and December 2010 were enrolled and eliminated according to the inclusion and exclusion criteria. GAR was defined as the absolute globulin value divided by the absolute albumin value. Chi-squared test was performed to compare clinical characteristics in different groups. Kaplan-Meier and Cox regression model were used to determine independent prognostic factors. A P value of ≤0.05 was considered to be statistically significant.

Results

Total 316 patients were finally enrolled. The median progression free survival (PFS) and overall survival (OS) were 210.0 and 430.0 days, respectively. The statistical analyses indicated that pretreatment GAR >0.58 [hazard ratio (HR) =1.52, 95% confidence interval (95% CI): 1.12-2.08, P=0.008 for PFS, HR =1.65, 95% CI: 1.20-2.26, P=0.002 for OS], and pretreatment albumin ≤35 g/L (HR =2.09, 95% CI: 1.20-3.65, P=0.003 for PFS, HR =1.92, 95% CI: 1.10-3.36, P=0.022 for OS) were independent prognostic factors for both PFS and OS.

Conclusions

Our study first established a connection between pretreatment GAR and advanced NSCLC patients, suggesting that GAR was an independent prognostic factor and could be the biomarker for prognosis.     

Non-surgical therapy for the patients with advanced non-small cell lung cancer

Abstract Radiation therapy (RT) and chemotherapy have been the two main treatment modalities for advanced non-small cell lung cancer (NSCLC). New techniques in RT, including hyperfractination and 3-dimensional conformal RT (3-DCRT), have changed conventional RT, which has been regarded as standard modality for locally advanced NSCLC. Introduction of cisplatin into chemotherapeutic regimens for NSCLC has changed the status of chemotherapy to standard therapy for patients with stage IV or stage IIIb with effusion. Radiation therapy or chemotherapy alone have already showed their limitations, even although they could improve the survival of NSCLC patients. Combined treatments with these two have become powerful alternatives for patients with unresectable and locally advanced NSCLC. Sequential or concurrent chemoradiotherapy could improve the response rate and survival rate without a remarkable increase in toxicities. Gene therapy is a novel therapeutic approach based on molecular oncology and tumour immunology. The practical contribution of gene therapy to clinical oncology is still minimal. From the research data, gene therapy has shown its potential to become a new treatment modality or to lead us to as yet undiscovered novel approaches to the treatment of lung cancer.     

非小细胞肺癌患者外周血CCNB1IP1及c-Cbl基因突变研究

目的检测NSCLC患者外周血c-Cbl和CCNB1IP1基因突变情况。方法收集20例健康人、20例肺结核和40例NSCLC患者外周血标本,采用RT-PCR和基因测序方法,检测c-Cbl和CCNB1IP1基因突变。结果所有标本中均未检测出CC-NB1IP1基因突变;而仅在NSCLC患者外周血检测到4种c-Cbl基因突变,突变率为20%;突变率与患者的性别、年龄及病理学分型均无相关性(P>0.05);而不同临床分期间突变率不同,差异有统计学意义(P<0.05)。结论 NSCLC患者外周血中检测到c-Cbl基因突变,且不同临床分期间突变率不同。     

Elevated platelet count is a strong predictor of poor prognosis in stage I non-small cell lung cancer patients

Stage I non-small cell lung cancer (NSCLC) show a highly variable biological behavior which cannot be accurately predicted by the current available prognostic markers. Platelet plays a significant role in cancer cell growth, progression and metastasis. This study aimed to investigate whether preoperative platelet count correlate with clinical prognosis in localized NSCLC. A retrospective clinical analysis was designed for a total of 234 stage I NSCLC patients in our hospital between October 2006 and December 2009. Pre-operative platelet count was measured. The association of platelet count with clinical pathological factors and patient outcome was evaluated. A significant correlation was detected between platelet count and tumor cell differentiation and T stage. Patients with elevated platelet count had an elevated risk of disease progression and death compared to patients with normal platelet count. The hazard ratio was 5.314 (95% confidence interval [CI] 2.750–10.269) for disease progression and 3.139 (95% CI 1.227–8.034) for death. The trend linking increasing platelet count with risk was also statistically significant for both the outcomes (p?<?0.05). These finding demonstrate that preoperative platelet count is a useful predictor of high risk progression and poor prognosis in stage I NSCLC patients.     

Dynamic nomogram for long-term survival in patients with non-small cell lung cancer after pneumonectomy

BackgroundThe study aims to identify prognostic factors of overall survival (OS) in patients who had pneumonectomy, in order to develop a practical dynamic nomogram model.MethodsA total of 2,255 patients with non-small cell lung cancer (NSCLC) who underwent pneumonectomy were identified from 2010–2015 in the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into a training (2011–2015) and a validation [2010] cohort. A nomogram and a risk classification system were constructed from the independent survival factors in multivariable analysis. The predictive accuracy of the nomogram was measured through internal and external validation.ResultsIndependent prognostic factors associated with OS were gender, age, pathology, tumor size, N stage, chemotherapy, and radiotherapy. The C-index of the nomogram for OS was 0.675 (95% CI: 0.655–0.694). Similarly, the AUC of the model was 0.733, 0.709, and 0.701 for the 1-, 3-, and 5-year OS, respectively. The calibration curves for survival demonstrated good agreement. Significant statistical differences were found in the OS of patients within different risk groups. An online calculation tool was established for clinical use.ConclusionsThis novel nomogram was able to provide a reliable prognosis for survival in patients with NSCLC undergoing pneumonectomy.     

血清VEGF对塞来昔布治疗晚期肺癌的预测作用

目的验证以下假设:治疗开始前的低水平血清VEGF预示存活时间较长,而环氧合酶-2(COX-2)抑制剂塞来昔布联合化疗能提高非小细胞肺癌(NSCLC)的缓解率和生存期。方法本试验为双盲单中心III期试验,选取81例IIIB或IV期NSCLC患者,ECOG体力状态评分为0-2入组。随机给予塞来昔布或安慰剂400 mg b.i.d联合4周期长春瑞滨/铂类化疗。塞来昔布计划给药时间最长1年,如疾病进展或出现严重毒性可停药。在治疗起始和4周期化疗结束后,检测所有患者血清VEGF水平。结果 81例患者治疗起始的VEGF水平中位值是340.98pg/m L。4周期化疗结束后VEGF平均值下降。总体生存期(OS)塞来昔布组vs安慰剂组为17.5月vs15.9月(P=0.837);无进展生存期(PFS)塞来昔布组vs安慰剂组为14.4月vs 7月(P=0.000)。治疗起始的VEGF水平≥340.98pg/m L组患者OS较VEGF水平340.98pg/m L组差(13.2月vs 26月,P=0.000),PFS也缩短(3.5月vs8.5月,P=0.000)。结论治疗前血清VEGF低水平能预示塞来昔布对生存期的正效应。     

Retreatment with pemetrexed chemotherapy in advanced non-small cell lung cancer patient

Objective

The aim of this study was to evaluate the feasibility and safety of retreatment the pemetrexed after the failure prior pemetrexed-based chemotherapy in non-small cell lung cancer (NSCLC) from our institute.

Patients and methods

Patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from Dec 2009 to Dec 2012 were retrospectively analyzed. All of the patients were given pemetrexed chemotherapy after the prior pemetrexed-based treatment. Survival analysis was evaluated by Kaplan-Meier method.

Results

Twenty-five patients were included in current study. Initial pemetrexed-based therapy was given as first-line treatment in all patients. Nine patients retreated with pemetrexed as the fourth-line treatment, and sixteen as further-line. One patient (4%) achieved partial response (PR), 9 (36%) with stable disease (SD), and 15 (60%) had progressive disease (PD). The disease control rate (DCR) was 40% and the median progression-free survival (PFS) was 1.5 months (95% CI: 0.8-2.4 months). Patients with an initial PFS >6 months had a median PFS after retreatment of 2.2 months, while patients with an initial pemetrexed PFS ≤6 months had a median PFS after retreatment of 1.1 months (P=0.036). The toxicities associated with the 2nd pemetrexed were generally acceptable.

Conclusions

Retreatment of pemetrexed seems to be a potential therapeutic option for treatment of selected advanced NSCLC patients after failure of initial pemetrexed therapy, especially for the patients with a PFS more than 6 months in the initial pemetrexed treatment.     

Long-term survival of more than 3 years among patients with advanced non-small cell lung cancer treated with chemotherapy

AIM: To evaluate the prognostic factors of long-term survival of more than 3 years in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the records of 474 patients with advanced IIIB/IV NSCLC who received chemotherapy as initial treatment between September 2002 and March 2007. RESULTS: The median survival time (MST) was 12.5 mo and the 3 year and 5 year survival rates were 14.6% and 5.3%, respectively. Long-term survival of more than 3 and 5 years was observed in 65 and 16 patients, respectively. The MST for the 65 patients was 61.5 mo (range, 60.1-81.0 mo). In the 474 patients, a good performance status (PS), female sex, non-smoking status and adenocarcinoma histology were significantly associated with a favorable outcome. Furthermore, female sex, a good PS, non-smoking status and adenocarcinoma histology were significantly correlated with long-term survival of more than 3 years and most of these patients (89.2%, 58/65) received epidermal growth factor receptor-tyrosine kinase inhibitors as any line treatment. Survival analysis of long-term survivors showed that a PS of 0 was an independent prognostic factor for predicting favorable outcomes. CONCLUSION: Our results suggest that a good PS and adenocarcinoma histology play an important role in long-term survival of more than 3 years. A PS of 0 was an independent prognostic factor for predicting favorable outcomes in patients with advanced NSCLC who survived for more than 3 years.     

Enhanced expression of FGF19 predicts poor prognosis in patients with non-small cell lung cancer

BackgroundLung cancer is one of the most common cancers and a leading cause of cancer-related death worldwide. Although many treatment options exist for lung cancer, some patients still suffer postoperative recurrence, and a consequent reduction of overall survival (OS). Our study aimed to investigate the correlation of FGF19 expression with the clinicopathological features and survival outcomes of non-small cell lung cancer (NSCLC) patients.MethodsBioinformatics analysis was conducted using the data from The Cancer Genome Atlas (TCGA) database to distinguish between the FGF19 levels of tumor and normal tissue and to determine their correlation with the OS. A total of 187 NSCLC patients who underwent radical resection of lung cancer were enrolled, and tissues were collected to determine FGF19 expression by immunohistochemistry (IHC) assay. Clinicopathological features including the survival date were collected for detailed research.ResultsAccording to the analysis based on the TCGA database, we found that the NSCLC tissues exhibited enhanced FGF19 messenger RNA (mRNA) expression and that the FGF19 mRNA levels correlated with shorter OS in NSCLC patients. IHC staining indicated that 88 (47.1%) patients had high FGF19 expression and 99 (52.9%) patients had low FGF19 expression. Meanwhile, survival data showed that high FGF19 expression was correlated with reduced OS (P<0.001). Moreover, both the univariate analysis and the forward stepwise multivariate Cox regression revealed that high FGF19 expression was an independent prognostic factor for decreased OS (P=0.001).ConclusionsThe expression of FGF19 is significantly upregulated in NSCLC, and the overexpression of FGF19 is correlated with poor OS, especially in lung adenocarcinoma (LUAD) cases. FGF19 might serve as a potential biomarker for predicting poor OS in NSCLC patients.