Synchronous neuroendocrine tumor and non‐small‐cell lung cancer in neurofibromatosis type 1

Neurofibromatosis type 1 is a common cancer predisposing condition. Tumors, particularly gastrointestinal tumors, are commonly associated with NF1 but are not widely known. In addition, the relationship between lung cancer and neurofibromatosis has been controversial until recently with the discovery of oncogenes such as p53.     

Bioinformatics analysis of differentially expressed miRNAs in non‐small cell lung cancer

ObjectiveNon‐small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype‐specific molecular therapeutic procedures.MethodsA total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.ResultsLUAD and LUSC appear sharply distinct at molecular and pathological level. Let‐7a‐5p, miR‐338, miR‐375, miR‐217, miR‐627, miR‐140, miR‐147b, miR‐138‐2, miR‐584, and miR‐197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2‐1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let‐7a‐5p was significantly down‐regulated in LUAD while miR‐338 was markedly down‐regulated in LUSC. Bioinformatics analyses appeared that let‐7a‐5p directly targets high–molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2‐1) which was associated with tumor progression in LUSC was identified as a target gene of miR‐338.ConclusionsDistinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype‐specific molecular therapeutic target to protect against LUAD and LUSC.     

Aberrant methylation of mutL homolog 1 is associated with increased risk of non‐small cell lung cancer

Background

Non‐small cell lung cancer (NSCLC) is a common malignant tumor. DNA hypermethylation in the promoter region has been served as a potential molecular marker for several tumors. The goal of the current study was to assess the diagnostic ability of mutL homolog 1 (MLH1) promoter methylation in NSCLC.

Methods

A total of 111 NSCLC patients’ paired tissue samples were obtained to explore the association between MLH1 promoter methylation and NSCLC by methylation‐specific polymerase chain reaction (MSP) method. Public databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to verify our findings.

Results

Our results showed a significantly higher MLH1 methylation frequency in tumor tissue samples than their paired adjacent tissues (P = .008). ROC curve indicated that MLH1MSP assay was a sensitive but not a specific method in the diagnosis for NSCLC (sensitivity = 0.964, specificity = 0.135, AUC = 0.550). And the association between the methylation level and clinical characteristics has no statistical significance. TCGA cohort evinced a higher methylation probability in tumor group compared with nontumor group (the mean β value: −0.449 [−0.467, −0.437] vs −0.466 [−0.472, −0.437], P = .011), which was consistent with our results. Meanwhile, an inverse correlation between MLH1 methylation and MLH1 expression was detected in TCGA and GEO databases.

Conclusions

The MSP method for MLH1 methylation was a sensitive but not a specific diagnostic method for NSCLC.

     

康莱特联合化疗对中老年晚期非小细胞肺癌患者生存质量的影响

目的观察康莱特联合化疗对中老年晚期非小细胞肺癌患者生存质量的影响。方法47例中老年晚期非小细胞肺癌患者随机分为康莱特加化疗组(康莱特组)26例及单纯化疗组(化疗组)21例,就生存质量进行比较。结果康莱特组与化疗组比较,疼痛缓解率、KPS评分、体重评分、及生存质量评分有明显提高,统计学处理均有显著性差异(P<0.01)。结论康莱特能明显控制癌痛,增加患者体重,并提高患者生存质量。     

晚期非小细胞肺癌患者预后相关因素分析

目的 探讨晚期非小细胞肺癌预后的相关因素。方法 对234例晚期非小细胞肺癌患者的临床资料进 行回顾性分析,对可能影响其预后的相关因素进行单因素和多因素分析。结果 符合纳入标准的非小细胞肺癌患者 234例,选择性别、年龄、吸烟状况、功能状态(PS)评分、病理类型、临床分期6个因素进行单因素分析,其结果显示:PS 评分的相对危险度是1.980(95%CI =1.482~2.646,P <0.05),吸烟状况的相对危险度是1.355(95%CI =1.029~ 1.784,P <0.05),提示PS评分及吸烟状况对晚期非小细胞肺癌预后有影响。针对上述两个因素进一步行多因素 COX分析显示:PS评分的相对危险度是2.085(95%CI =1.555~2.796,P <0.05),吸烟状况的相对危险度是1.464 (95%CI =1.109~1.934,P <0.05),提示PS评分、吸烟状况是影响晚期非小细胞肺癌预后的独立因素。结论 PS评分、吸烟状况是影响晚期非小细胞肺癌生存的独立预后因素。     

Transformation of non-small cell lung cancer into small cell lung cancer in a patient with advanced lung cancer: a case report

Targeted therapy in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often fails because of drug resistance. Here, we report a 57-year-old male patient with stage IV small cell lung cancer (SCLC) transformation during targeted therapy. Chest computerized tomography (CT), hematoxylin and eosin histological examination, immunohistochemistry, allele refractory mutation system‐based quantitative polymerase chain reaction analysis of EGFR point mutations, and next-generation sequencing were performed for diagnosis and therapeutic efficacy evaluation. A combination of chest CT, histological examination, and immunohistochemistry confirmed the initial NSCLC diagnosis. Next-generation sequencing detected only EGFR exon 19 deletion (ex19del) before treatment and later identified EGFR exon20p.T790M point mutation, EGFR amplification, myc proto-oncogene (MYC) amplification, retinoblastoma 1 (RB1) mutation, and tumor protein 53 (TP53) mutation. Histology and immunohistochemistry revealed transformation from NSCLC to SCLC during treatment, which eventually returned to NSCLC. Drug resistance to targeted therapy for patients with NSCLC frequently occurs because of EGFR exon20p.T790M point mutation, TP53 mutation, RB1 mutation, and MYC amplification. These mutations are also the major determining factors of NSCLC outcomes. Therefore, next-generation sequencing should be performed to confirm drug efficacy during targeted therapy for NSCLC.     

血清标志物pro-GRP、NSE在小细胞肺癌鉴别诊断中的价值

目的探讨血清标志物胃泌素释放肽前体(pro-GRP)、神经元特异性烯醇化酶(NSE)对小细胞肺癌(SCLC)鉴别诊断的价值。方法选择SCLC患者120例(SCLC组)、非小细胞肺癌(NSCLC)患者130例、良性肺部疾病者80例,以及同期健康体检者90例(健康对照组),检测血清pro-GRP、NSE水平,SPSS13.0进行统计分析,分析各标志物的血清水平和阳性率。Graph-Pad Prism 5进行ROC曲线绘制。结果 SCLC组患者血pro-GRP、NSE水平明显高于NSCLC组、良性肺部疾病组和健康对照组,差异有统计学意义(P0.05)。SCLC组患者血清pro-GRP阳性率(80.00%)高于其他3组,差异有统计学意义(P0.05)。SCLC组和NSCLC组NSE阳性率比较差异无统计学意义(P0.05)。pro-GRP、NSE单独及联合诊断SCLC的ROC曲线下面积分别为0.890、0.810和0.915。结论 NSE只能鉴定良恶性肺部疾病,不能鉴定SCLC和NSCLC;pro-GRP既可鉴定良恶性肺部疾病,还可鉴定肺癌的SCLC和NSCLC病理分型;pro-GRP、NSE联合检测对SCLC的鉴别诊断有重要价值。     

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

BackgroundImmunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC.MethodsSerum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel.ResultsThe expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively.ConclusionsTIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.     

非小细胞肺癌新辅助化疗疗效评价进展

术前新辅助化疗已成为非小细胞肺癌患者的标准化治疗方案,随着新辅助化疗在临床治疗中的广泛应用,疗效评价显得尤为重要。如何能无创、及时、准确、有效的评价化疗疗效已成为临床研究的重点。目前临床上通常采用影像学及病理学检查等方法,同时对非小细胞肺癌生物学因子的研究也在迅速开展。现将各种评价方法的应用现状作一综述。     

吉非替尼联合西黄丸治疗晚期非小细胞肺癌的疗效评价

目的 评价吉非替尼联合西黄丸治疗晚期非小细胞肺癌的临床疗效.方法 选取2015年9月至2018年12月我院收治的晚期非小细胞肺癌患者21例为研究对象,所有患者均接受吉非替尼联合西黄丸治疗,观察患者的近期疗效.结果 21例患者中,疾病稳定(SD)10例,部分缓解(PR)8例,疾病进展(DP)3例,完全缓解(CR)0例,疾病缓解率(DRR)38.09％(8/21),疾病控制率(DCR)85.71％(18/21).用药治疗后随访6～24个月,36例患者中死亡3例,无进展生存期(PFS)5～14(7.12±0.93)个月,总生存期(OS)6～24(10.23±1.10)个月.用药期间,出现恶心、呕吐Ⅰ度1例(4.76％);AST/ALT水平升高Ⅱ度1例(4.76％);皮疹Ⅰ度4例(19.04％)、Ⅱ度1例(4.76％);腹泻Ⅰ度2例(9.52％).结论 吉非替尼联合西黄丸可以显著改善晚期非小细胞肺癌本身及与治疗有关的热证或热毒证的症状,提高生存质量,延长生存时间,减轻毒副作用的发生率及程度,值得推广应用.