Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Exploring the impact of non-small cell lung cancer tumor microbiome on the efficacy of chemotherapy and immune checkpoint inhibitors

Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.

EGFR-TKI单药与传统化疗方案治疗进展期NSCLC安全性的网状meta分析

目的对一至三代表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)与传统化疗方案治疗进展期非小细胞肺癌(NSCLC)的安全性进行比较,同时采用网状meta分析方法评价三代EGFR-TKI与一、二代之间的安全性。方法检索PubMed、Embase、Cochrane图书馆、中国生物医学文献数据库、中国知网、万方数字化期刊全文数据库、维普数据库,检索时限均为从建库至2020年12月,搜集EGFR-TKI单药对比铂类为基础培美曲塞化疗方案的随机对照试验(RCT)。筛选文献、提取资料,并用Cochrane系统评价偏倚风险评估工具对纳入研究的RCT进行偏倚风险评估,采用RevMan 5.3软件、STATA 15.1软件进行meta分析。结果meta分析结果显示,试验组(EGFR-TKI单药)、对照组(培美曲塞联合铂类)患者的腹泻[相对危险度(RR)=2.16,95%置信区间(CI)0.742~6.297,P>0.05]、便秘(RR=0.44,95%CI 0.187~1.039,P>0.05)发生率比较差异均无统计学意义。试验组白细胞减少发生率、中性粒细胞减少发生率、贫血发生率、血小板减少发生率、食欲不振发生率、恶心发生率均低于对照组(RR=0.21,95%CI 0.10~0.41,P<0.001;RR=0.21,95%CI 0.08~0.55,P<0.001;RR=0.26,95%CI 0.13~0.51,P<0.001;RR=0.39,95%CI 0.24~0.64,P<0.001;RR=0.39,95%CI 0.28~0.55,P<0.001;RR=0.30,95%CI 0.24~0.37,P<0.001);试验组皮疹发生率高于对照组(RR=9.63,95%CI 6.30~14.72,P<0.001)。对一至三代EGFR-TKI的不良反应进行网状meta分析结果显示,三代EGFR-TKI奥希替尼组白细胞减少发生率要高于一、二代EGFR-TKI,贫血发生率与埃克替尼组相似,但高于吉非替尼组和阿法替尼组(均P<0.05)。结论一至三代EGFR-TKI的血液系统、消化系统不良反应发生率均低于传统化疗方案;三代EGFR-TKI与一、二代相比,在白细胞减少及贫血发生率方面各具优势。

基于UHPLC-MS技术的NSCLC血浆生物学标志物的筛选及鉴定研究

目的研究UHPLC-MS技术的NSCLC血浆生物学标志物的筛选及鉴定。方法本研究纳入符合非小细胞肺癌临床诊断标准的60例NSCLC患者,随机分为两组,接受靶向治疗(TACE)的非小细胞肺癌患者为鉴别诊断组,未接受靶向治疗的NSCLC患者为正常对照组。结果在60例NSCLC患者中,通过LC-MS/MS技术共检测到552个生物标志物。在其中17个生物标志物中,有8个出现在已知的EGFR突变患者中,另7个出现在ALK融合患者中,6个出现在HER2突变患者中。此外,NSCLC患者血浆中含有丰富的非编码RNA(miRNA),包括58个miRNA和23个mRNA。结论本研究中,采用LC-MS/MS技术对NSCLC患者血浆进行分析,可快速、高效地获得血浆样品中的生物学标志物。这些标志物可以作为NSCLC诊断的潜在生物学标志物,并且可以用于预测肿瘤进展和不良预后。

High expression of PD-L1 mainly occurs in non-small cell lung cancer patients with squamous cell carcinoma or poor differentiation

Background:Lung cancer is one of the most lethal cancers worldwide,but studies have shown that the higher the expression of programmed cell death protein 1 ligand 1(PD-L1)in non-small cell lung cancer(NSCLC),the more likely it will benefit from anti-PD-L1 immunotherapy.The purpose of our study was to collect and analyze abundant clinical samples in order to provide evidence for clinicians and patients who might consider anti-PD-L1 immunotherapy while jointly formulating treatment plans.Methods:On the one hand,we obtained cases from The Cancer Genome Atlas(TCGA)database,including 498 lung squamous cell cancer(LUSC)patients and 515 lung adenocarcinoma(LUAD)patients.We studied the lung caner driver gene in LUSC and LUAD.On the other hand,PD-L1 expression was detected in lung cancer tissues of 1,008 NSCLC patients with immunohistochemistry staining(IHC),and we studied the correlation between PD-L1 protein expression and clinicopathological characteristics.Results:PD-L1 expression was higher in LUSC than in LUAD at the mRNA level.In univariate analysis,PD-L1 expression at the protein level was higher in patients who were males,were LUSC,were smokers,had a tumor diameter>3 cm,had poor differentiation,or had stages Ⅲ-Ⅳ disease.In multivariate analysis,PD-L1 expression was higher in patients who were LUSC or in poor differentiation.Conclusion:In term of protein level,PD-L1 expression was higher in NSCLC patients who were LUSC or in poor differentiation.We recommend that PD-L1 IHC detection can be routinely performed in such populations that are likely to benefit most from PD-L1 immunotherapy.

炙甘草汤加减联合PD-1治疗晚期NSCLC(气阴两虚型)的疗效

目的:分析炙甘草汤加减联合程序性死亡受体1(programmed cell death protein-1,PD-1)治疗晚期非小细胞肺癌(nonsmall cell lung cancer,NSCLC)(气阴两虚型)的临床疗效。方法:回顾性分析2020年12月至2022年12月就诊于吉林省肿瘤医院、长春中医药大学附属医院的晚期NSCLC(气阴两虚型)患者72例,随机分为两组各36例,对照组(PD-1单抗)、治疗组(PD-1单抗联合炙甘草汤加减)。主要观察指标为免疫功能(CD3^(+)、CD3^(+)/CD4^(+)、CD3^(+)/CD8^(+))和生存质量评分(KPS),次要观察指标为客观缓解率(objective response rate,ORR)、中医症候积分、血清肿瘤标志物癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白片段(CYFRA211)、免疫相关不良反应(胃肠毒性、肺毒性、肝毒性、甲状腺毒性)发生率。结果:治疗组在调节免疫功能CD3^(+)、CD3^(+)/CD4^(+)、CD3^(+)/CD8^(+),提高患者生存质量在T3时间点、T4时间点、降低肿瘤标志物CEA、CY211、改善中医证候咳嗽、乏力、心悸、腹泻的症状和减少免疫相关性肺炎、腹泻方面,均优于对照组(P<0.05)。两组患者客观缓解率分别为治疗组36.1%,对照组25.0%,无显著性差异(P>0.05)。结论:炙甘草汤加减联合PD-1治疗晚期NSCLC的患者,可以显著增强免疫功能,提高临床疗效,减少免疫相关不良反应且安全性较好。

CHMP4C通过调控PI3K/AKT信号通路影响NSCLC细胞增殖与凋亡

目的:探究染色质修饰蛋白4C(CHMP4C)对非小细胞肺癌(NSCLC)进展及顺铂敏感性的影响及其机制。方法:通过免疫组化检测CHMP4C在NSCLC癌组织和癌旁组织中的表达情况。利用实时荧光定量PCR(RT-qPCR)和蛋白免疫印迹法(Western blot)检测CHMP4C在NSCLC细胞系中的表达水平。细胞计数试剂盒(CCK-8)和细胞克隆实验检测细胞活力及半数抑制浓度IC50;流式细胞术检测细胞周期和凋亡。Western blot分析细胞凋亡相关蛋白(caspase 3、Bad)及PI3K/AKT信号通路中关键蛋白的表达水平。另外,我们采用动物模型进一步验证CHMP4C对体内肿瘤生长的影响。结果:CHMP4C在NSCLC癌组织和细胞系中高表达,与肿瘤T分期显著相关(P<0.05)。敲低CHMP4C抑制细胞增殖,促进细胞凋亡,并将细胞阻滞在S期(P<0.05)。敲低CHMP4C可抑制PI3K/AKT信号通路活化,然而激活PI3K/AKT信号通路逆转了CHMP4C敲低对NSCLC细胞的影响(P<0.05)。利用顺铂处理细胞后发现NSCLC细胞生长受抑制,且CHMP4C表达降低;敲低CHMP4C联合顺铂治疗明显诱导肿瘤细胞凋亡,抑制肿瘤细胞增殖(P<0.05)。在动物实验中,CHMP4C敲低的肿瘤体积小于对照组,其ki67表达显著降低,而caspase 3表达升高(P<0.05)。结论:CHMP4C在NSCLC癌组织及细胞系中高表达,在体内及体外实验中敲低CHMP4C可抑制NSCLC细胞增殖,促进细胞凋亡,增强顺铂治疗的敏感性;CHMP4C可能通过PI3K/AKT信号通路参与NSCLC进展与顺铂耐药。

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L150%or more(EMPOWER-Lung 1):35-month follow-up from a multicentre,open-label,randomised,phase 3 trial

肺癌是全球癌症相关死亡的主要原因,非小组胞肺癌(NSCLC)占所有肺癌病例的80%-85%。随着分子生物学的发展,针对驱动基因突变(如EGFR、ALK等)的靶向药物治疗已成为晚期NSCLC的标准一线治疗。但大多数NSCLC并没有可检测到的驱动基因突变,传统的铂类化疗效果不佳。免疫检查点抑制剂的出现极大地改变了这一领域的治疗格局。PD-1/PD-L1抑制剂已被证实可以显著提高NSCLC患者的疗效和生存期,特别是PD-L1表达阳性率≥50%的人群。

Expressions of Osteopontin (OPN),αVβ3 and Pim-1 Associated with Poor Prognosis in Non-small Cell Lung Cancer (NSCLC)

Objective： To examine the expressions ot osteopontin （OPN）, αvP3 and Pim-1 in non-small cell lung cancer （NSCLC）, and investigate their potential pathogenic roles in the development of NSCLC. Methods： Immunohistochemistry was used to examine the expressions of OPN, αve3 and Pim-1 in cohort （136 cases） of NSCLC samples and their adjacent normal lung tissue specimens. Statistical analysis was performed to evaluate the relationships among expressions of OPN, αve3 and Pim-1 and their associations with patients clinico- pathological parameters. Results： The expressions of OPN and Pim-1 were predominantly observed in cytoplasm. The expression of αve3 was mostly detected in cytoplasm and/or membrane. In NSCLC samples, the positive rates of OPN, αve3 and Pim-1 expressions were 68.4% （93/136）, 77.2% （105/136） and 57.4% （78/136）, respectively. In normal lung tissues, in contrast, the positive rates of OPN, αve3 and Pim-1 were 24.0% （12/50）, 26.0% （13/50） and 16.0% （8/50）, respectively. There were significant differences of the positive expression rates of OPN, αve3 and Pim-1 between NSCLCs samples and normal lung tissues （P〈O.01）. In addition, the positive expression of OPN, αve3 and Pim-1 in NSCLCs samples was significantly associated with increased pathological grade, lymph node metastasis and advanced clinical stage （P〈O.01）, and they were independent of other clinicopathological parameters （P〉0.05）. Furthermore, a significantly positive correlation between the expression of OPN and αve3 （r=0.38, P〈O.O1）, OPN and Pim-1 （r=0.37, P〈O.01）, or av133 and Pim-1 （r=0.20, P〈0.05） was evaluated in our NSCLC cohort. Conclusion： OPN, αve3 and Pim-1 proteins are frequently overexpressed in NSCLC, and they may play important roles in the development and/or progression of NSCLC.

Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations： a report of seven cases and literature review

Brain metastasis(BM)arising from non-small cell lung cancer(NSCLC)with rare epidermal growth factor receptor(EGFR)mutations is quite rare.The prognosis and therapeutic effects of BM remain enigmatic.To the best of our knowledge,this is the first report to make a separate analysis of BM from NSCLC patients with original uncommon EGFR mutations.We retrospectively reviewed 7 cases of BM arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical University Cancer Institute and Hospital.We also performed a literature review to assess therapeutic features and outcomes.

Predictive factors associated with gefitinib response in patients with advanced non-small-cell lung cancer(NSCLC)

Purpose： A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in advanced non-small-cell lung cancer （NSCLC）. This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. Patients and methods： EGFR gene typing in 33 advanced NSCLC patients received gefitinib （250 mg/day） were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively. Results： The overall objective response rate （ORR） and median progression-flee survival （PFS） in the 33 patients treated by gefitinib were 45.5% and 3.0 （2.0-4.0） months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients （P〈0.01）. Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients （P〈0.05, P〈0.01, respectively）. However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR （P〈0.01）. Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS （P〈0.05）. Conclusions： EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.

Treatment with Intensity-Modulated Radiation Therapy (IMRT) and Chemotherapy in Advanced Inoperable Non-Small Cell Lung Cancer (NSCLC): Toxicity, Survival and Patterns of Failure in Relation to Treatment with High and Low Radiation Dose

Purpose: To investigate the toxicity, survival and patterns of failure in patients with advanced lung cancer treated with intensity modulated radiation therapy (IMRT) and chemotherapy. Methods and Materials: Retrospective chart review of 68 total patients: 46 academic and 22 community center. Endpoints: Grade ≥ 3 pneumonitis, Grade ≥ 2 esophagitis, local, regional and distant failure, progression-free survival (PFS) and overall survival (OS). Results: For the academic center patients, median follow-up was 19.2 months. Esophagitis: 0% Grade 3, 35% Grade 2, no significant difference between dose bins: <70 Gy vs. 70 Gy, 25% vs. 45% (p = 0.22), <66 Gy vs. 66 - 70 Gy, 28% vs. 39% (p = 0.53). Lung dose metrics and PTV size were not associated with Grade ≥ 3 pneumonitis. Esophageal V35, V50, and mean dose but not PTV size was associated with Grade 2 esophagitis. 1 year local, regional and distant failure = 6.5%, 6.5%, and 30.4%. No endpoint differences were seen between dose bins, though patients with smaller PTVs treated with 70 Gy did demonstrate improved OS (ns) when compared to those treated with <70 Gy. Community Center: Median follow-up 6.2 months with 15% Grade 2 esophagitis, no Grade 3 esophagitis. Two patients (9%) experienced Grade ≥ 3 pneumonitis. Conclusions: IMRT chemoradiation was well tolerated in a population with advanced NSCLC both in the academic and community settings. Severe pneumonitis rates were low and comparable to other series using IMRT and chemotherapy. Esophagitis was mild and associated with V35, V50 and mean dose. No significant benefit was seen for higher doses regarding survival, local, regional or distant control despite that higher dose bins had smaller tumors. Though not statistically significant, we did find a trend toward worse OS for <70 Gy when the PTV was less than the median PTV.

贝伐珠单抗联合TP化疗方案治疗晚期NSCLC的疗效及预后观察

目的探讨贝伐珠单抗联合TP(紫杉醇+顺铂)化疗方案治疗晚期非小细胞肺癌(NSCLC)的疗效及对预后的影响。方法选取晚期NSCLC患者78例,随机分为A组(39例,予以TP化疗方案)和B组(39例,予以TP化疗方案+贝伐珠单抗)。比较2组的客观缓解率(ORR)、疾病控制率(DCR)和血清肿瘤标志物[血管内皮生长因子(VEGF)、细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)]水平。记录治疗期间肝肾功能损害、白细胞减少、中性粒细胞减少、血小板减少、胃肠道反应等不良反应发生情况。自实施治疗日始对患者进行随访,统计2组患者的5年生存率、无进展生存期(PFS)和总生存期(OS)。结果B组ORR、DCR分别为58.97%、89.74%,分别高于A组的35.90%、71.79%(P<0.05)。治疗后2组血清VEGF、CYFRA21-1、CEA水平均降低,且B组低于A组(P<0.05)。2组肝、肾功能损害,白细胞减少,中性粒细胞减少,血小板减少,胃肠道反应发生率均无明显差异(P>0.05)。B组5年生存率为20.51%,与A组(12.82%)相比无明显差异(P>0.05)。Kaplan-Meier生存曲线显示,B组的中位PFS长于A组(8.9 vs 7.2个月)(P<0.05);B组的中位OS长于A组(25.6 vs 17.9个月)(P<0.05)。结论相比于TP化疗方案治疗晚期NSCLC,联合贝伐珠单抗可提高ORR和DCR,延长PFS和OS,且可降低VEGF、CYFRA21-1、CEA肿瘤标志物水平。

深度学习与机器学习预测NSCLC的N分期

本文利用深度学习和机器学习技术,提出一种基于PET和CT图像的非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)肿瘤N分期预测方法,以提高N分期的准确率和稳定性。使用深度学习残差神经网络3D Resnet50提取NSCLC的CT与PET影像特征,并将特征降维到32维;将多模态特征进行拼接,输入机器学习模型进行NSCLC的N分期预测。最终,本文所提出的基于深度学习和机器学习预测NSCLC肿瘤分期预测方法的预测准确率在训练集达到了1.0,测试集上达到了0.852,平均受试者工作特征曲线下面积(Receiver Operating Characteristic,ROC)超过了0.91。实验表明,基于深度学习和机器学习的NSCLC肿瘤预测方法可以提高非小细胞肺癌N分期的准确率和稳定性,具有良好的应用前景和实际应用价值。

Silencing ribosomal protein L4 enhances the inhibitory effects of triptolide on non-small cell lung cancer cells by disrupting the mouse double minute 2 protein–P53 tumor suppressor pathway

Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanisms through which TP inhibits NSCLC are well understood,those that involve ribosomal proteins remain yet to be understood.In this study,the transcriptome and proteome were integrated and analyzed.Our data indicated ribosomal protein L4(RPL4)to be a core hub protein in the protein-protein interaction network.RPL4 is overexpressed in NSCLC tissues and cells.Transfection with siRPL4 or TP treatment alone arrested the cell cycle in the G1 phase,induced cell apoptosis,and repressed cell invasion.Compared to treating cells with TP alone or siRPL4,treating them with siRPL4–TP enhanced the inhibition of NSCLC cells.Reduced RPL4 expression reinforced the inhibitory effects of TP on NSCLC cells by disrupting the MDM2-P53 pathway and by altering the expression of PARP1/Snail/cyclin D1.In vivo assays verified that TP induced cell apoptosis and reduced RPL4 expression in xenografts.These findings provide clues to facilitate the development of effective TP-based therapeutic strategies to kill NSCLC cells.

CircUCP2 promotes the tumor progression of non-small cell lungcancer through the miR-149/UCP2 pathway

Non-small cell lung cancer(NSCLC)is a highly lethal cancer,and better treatments are urgently needed.Many studies have implicated circular RNAs(circRNAs)in the progression of multiple malignant tumors.Nonetheless,the functions of circRNAs in NSCLC remain unclear.To study new targets for the treatment of NSCLC,circRNA expression profiling was performed on NSCLC tissues and para-carcinoma nonmalignant tissues.RNA was isolated and used for circRNA sequencing.Biological studies were performed in vitro and in vivo to determine the functions of circRNAs in NSCLC,including their functions in cell proliferation and migration.How circRNAs function in NSCLC was explored to clarify the underlying regulatory mechanisms.We found that circUCP2 was upregulated in NSCLC tissues compared with neighboring nonmalignant tissues.circUCP2 promoted the proliferation and metastasis of NSCLC cells.circUCP2 promoted NSCLC progression by sponging miR-149 and upregulating UCP2.The circUCP2/miR-149/UCP2 axis accelerates the progression of NSCLC,and circUCP2 may therefore be a novel diagnostic biomarker for the progression of NSCLC.

Exploration of Kras Mutations and Their Potential for Being a Target Molecule in Cancer Chemotherapy

The Rat sarcoma virus (RAS) family of proteins, which includes the Kristen Rat sarcoma virus (KRAS), is linked to nearly one-fourth of all human cancers. KRAS mutations, in particular, are associated with Non-Small Cell Lung Carcinoma (NSCLC), colorectal cancer, adenocarcinomas, ovarian carcinoma, and endometrial tumors. KRAS activates 80 different signaling pathways, including Mitogen-activated protein kinases (MAPK) and Phosphoinositide 3-kinase (PI3K), and up-regulates transcription factors such as ETS like Protein (ELK), Jun Proto-Oncogene (JUN), and Myelocytomatosis (MYC), which are involved in cell differentiation, proliferation, transformation, and survival. KRAS mutations are also known to cause autocrine function, which further exacerbates the situation. In NSCLC, KRAS mutations have a strong positive correlation with the disease, particularly in patients with a smoking history. In pancreatic cancer, KRAS mutations are a dominant pathological basis, with most mutations being G12D, G12V, G13D, G13C, G13S, and G13R. These mutations serve as initial markers in tumorigenesis and are associated with poor prognosis and high mortality rates. In colorectal cancer, KRAS mutations contribute to 4/5 of cases, with cellular mechanisms involving the MAPK pathway, which resists anti-epidermal growth factor antibodies. In Low-grade Serous Ovarian Cancer (LGSOC), KRAS mutations are associated with altered signaling in the MAPK pathway and drug resistance. However, treatments such as Selumetinib, a down regulator of RAS/Rapidly Accelerated Fibrosarcoma (RAF)/Mitogen-activated protein kinase (MEK) pathways, and a combination of trametinib and buparlisib have shown promise in managing LGSOC when diagnosed early through KRAS mutation markers. Although KRAS mutations are commonly associated with many types of cancer, their use in clinical practice is limited due to the lack of accurate methods to identify them. It is needed to further isolate the KRAS mutation products and correlate the cancer-causing genes to make it a promising approach for cancer chemotherapy.

Elevated pretreatment plasma fibrinogen level is associated with metastasis of non-small cell lung cancer(NSCLC)

Objective The aim of this study was to investigate the correlation between pretreatment fibrinogen levels and metastasis in non-small cell lung cancer(NSCLC).Methods The study included 503 NSCLC patients with a clear pathological diagnosis and 168 patients diagnosed with benign lung diseases by histological examination.Pretreatment plasma fibrinogen values were quantified,and the relationship between plasma fibrinogen level and clinical variables comprising tumor size,metastasis,and clinical stage was examined using Kruskal-Wallis test,Wilcoxon rank sum test,and Chi-square test.Results The median plasma fibrinogen values were statistically higher in NSCLC patients with metastasis than patients with benign lung diseases and NSCLC patients without metastasis(Kruskal-Wallis test;P<0.001).Plasma fibrinogen values were also significantly higher in advanced clinical stages(Wilcoxon rank sum test;P<0.001).A significant relationship was observed between elevated fibrinogen(>2.974 g/L)and metastasis,clinical stage,and tumor size(Chi-square test;P<0.001).Conclusion This correlation suggests that elevated pretreatment plasma fibrinogen levels can predict metastasis and advanced tumor stage in NSCLC patients.

胸腔镜辅助单孔与多孔肺段切除术治疗早期NSCLC的应用价值

目的探讨胸腔镜下单孔与多孔肺段切除术对早期非小细胞肺癌(Non-small cell lung cancer,NSCLC)患者代谢反应及心肺耐力的影响。方法选取2017年6月-2022年10月南通市第一人民医院早期NSCLC患者92例,根据简单随机数字表法分为多孔组与单孔组,各46例。单孔组采取胸腔镜单孔肺段切除术,多孔组采取胸腔镜多孔肺段切除术。比较两组围术期情况、术前及术后3 d代谢反应指标[视黄醇结合蛋白(Retinol-binding protein,RBP)、转铁蛋白(Transferrin,TRF)、前白蛋白(Prealbumin,PA)]水平、心肺耐力[6 min步行距离(6 min walking distance,6MWT)、疲劳指数、呼气峰流速(Peak expiratory velocity,PEF)、第1 s用力呼气容积(Forced expiratory volume 1 s,FEV1)]和并发症发生率。结果(1)两组手术时长、淋巴结清扫数目比较,差异无统计学意义(P>0.05),单孔组术中失血量、引流量少于多孔组,引流管放置时间、住院时长短于多孔组,差异有统计学意义(P<0.05)。(2)术后3 d两组PA、TRF、RBP水平较术前下降,但单孔组PA、TRF、RBP水平高于多孔组,差异有统计学意义(P<0.05)。(3)术后3 d两组6MWT、PEF、FEV1较术前降低,疲劳指数较术前增高,但单孔组6MWT、PEF、FEV1高于多孔组,疲劳指数低于多孔组,差异有统计学意义(P<0.05)。(4)单孔组并发症发生率(4.35%)低于多孔组(17.39%),差异有统计学意义(P<0.05)。结论采取胸腔镜单孔及多孔肺段切除术治疗早期NSCLC均可取得良好效果,但单孔术式可减少失血量,对代谢状态及心肺耐力影响较小,利于机体功能及早康复,且可降低并发症发生风险。