Background The involvement of certain adipokines link to carcinogenesis, development, and prognosis. However, the roles of adipokines in lung cancer and its histological subtypes remains indistinct. Therefore, the aims of this study are to explore the causal relationship between adipokines and lung cancers. Methods Summary-level data for exposures (six adipokines) and outcomes (lung cancer and its histological subtypes) were collected from the IEU OpenGWAS, International Lung Cancer Consortium (ILCCO) and lectures. Two-sample mendelian randomization (MR) was conducted to estimate the causality by employing single nucleotide polymorphisms (SNPs) as instrument variables (IVs). Human tissue microarray and immunohistochemistry (IHC) analysis validated the adipokines expression. Functional effects of LEPR in LUSC were assessed in vitro using NCI-H2170 and SK-MES-1 cell lines via siRNA-mediated knockdown, followed by assays for cell proliferation, invasion, and apoptosis. Results Leptin receptor (LEPR) was associated with risk of lung squamous cell carcinoma (LUSC, OR: 1.05, 95% CI: 1.01-1.08; P < 0.0125), and no other adipokines associated with lung cancer and its histological subtypes (P > 0.05). Experimental results revealed that high expression of LEPR in LUSC tumor samples compared to adjacent normal samples, and associated with unfavorable survival status. In vitro , LEPR knockdown significantly inhibited proliferation and invasion while promoting apoptosis in LUSC cells. Conclusion These findings suggest that LEPR may play a critical role in the development and progression of LUSC, providing a potential target for therapeutic intervention.

IntroductionSMARCA4‑deficient non‑small‑cell lung cancer (SMARCA4‑dNSCLC) is a rare, aggressive NSCLC subtype driven by SWI/SNF complex dysfunction with no standardized therapeutic strategies. Although chemoimmunotherapy represents standard first‑line therapy for driver‑negative advanced NSCLC, its real‑world efficacy in SMARCA4‑dNSCLC remains controversial. SMARCA4 loss frequently generates an immune‑desert tumor microenvironment with low PD‑L1 and sparse CD8⁺ T‑cell infiltration, potentially conferring intrinsic resistance to immune checkpoint inhibitors (ICIs). Pre‑clinical data suggest synergism between anti‑angiogenic agents and chemoimmunotherapy; however, real‑world evidence comparing chemoimmunotherapy alone versus chemoimmunotherapy plus anti‑angiogenics for SMARCA4‑dNSCLC is limited.MethodsThis single‑center retrospective cohort enrolled 22 patients with immunohistochemically‑confirmed advanced SMARCA4‑dNSCLC treated from January 2021 to September 2024. Clinicopathological characteristics, treatment regimens, survival outcomes and safety data were collected. The Kaplan‑Meier method was applied to estimate progression‑free survival (PFS) and overall survival (OS). Given the small sample size, only univariate survival analysis was performed. Objective response rate (ORR) and disease control rate (DCR) were evaluated per RECIST 1.1, and treatment‑related adverse events were graded using CTCAE v4.0. This study obtained local ethics‑committee approval with informed consent waived. The last follow‑up date was September 1, 2025.ResultsMost patients were elderly male smokers with high Ki‑67, frequent adrenal metastasis and low‑to‑negative PD‑L1 expression. Compared with non‑ICI‑based therapy, ICI‑containing regimens achieved significantly superior survival: median OS not reached versus 8.7 months (HR = 0.28, 95%CI:0.08‑0.98, P = 0.047), accompanied by improved PFS, ORR and DCR. Addition of anti‑angiogenic agents brought no extra survival benefit. Elevated CYFRA21‑1 and poor ECOG‑PS predicted unfavorable prognosis. Treatment‑related adverse events were generally tolerable across groups.ConclusionDespite an immune‑suppressed tumor microenvironment, real‑world ICI‑containing chemoimmunotherapy delivers meaningful survival benefits for advanced SMARCA4‑dNSCLC, whereas additional anti‑angiogenic combination yields no further clinical advantage. Our findings should be interpreted cautiously given retrospective design and small sample size. Large‑scale multi‑center prospective studies incorporating multivariable prognostic analyses are required to validate these results and optimize individualized treatment for this rare molecular NSCLC subtype.

Nasopharyngeal carcinoma (NPC) usually metastasizes to cervical lymph nodes, whereas inguinal lymph node metastases (ILNM) are rare, with only a small number of cases reported. ILNs are an uncommon site of secondary involvement, a phenomenon attributed to their unique anatomical and immunological features. The current study reported a case of NPC in which baseline positron emission tomography/CT showed metastasis from the left pharyngeal recess to the left cervical levels II-III. Mildly increased metabolic activity was observed in levels II-III of the right cervical chain, the left supraclavicular area and the bilateral inguinal area, initially interpreted as reactive hyperplasia. The patient was diagnosed with NPC (T2N1M0, stage IIA, 8th edition of the American Joint Committee on Cancer). At 5 months after the completion of induction chemotherapy and concurrent chemoradiotherapy, the bilateral ILNs showed interval enlargement and biopsy confirmed metastatic NPC. The patient was classified as stage IVB based on biopsy results, prompting appropriate treatment for this advanced stage. This rare case underscores the importance of considering ILNM as a possible metastatic site in NPC, requiring clinicians to perform timely evaluations and lymph node biopsies to prevent clinical understaging due to unrecognized occult metastatic disease, particularly during the early stages of diagnosis.

ABSTRACT Purpose In non‐small cell lung cancer (NSCLC) patients resistant to first‐ or second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), only half develop the T790M mutation and thus qualify for the treatment using third‐generation EGFR‐TKIs. For T790M‐negative patients, chemotherapy is the recommended second‐line treatment. We compared the efficacy between third‐generation EGFR‐TKIs and chemotherapy with or without first/second‐generation EGFR‐TKIs in T790M‐negative patients. Patients This study included T790M‐negative patients with EGFR‐mutated advanced NSCLC and progressing after first‐line treatment with first‐ or second‐generation EGFR‐TKIs. Data on clinical characteristics, disease features, and survival were collected, including general conditions, medical history, imaging, histology, and molecular profiling. Results Of 82 patients progressing after first‐ or second‐generation EGFR‐TKIs without acquiring T790M, 45 received third‐generation EGFR‐TKIs and 37 received chemotherapy and/or first/second‐generation EGFR‐TKIs. We found that third‐generation EGFR‐TKIs led to significantly longer median progression‐free survival (mPFS) than other treatments [10.20 months vs. 5.70 months, p = 0.017]. Subgroup analyses indicated that third‐generation EGFR‐TKIs had similar mPFS to the chemotherapy group but were significantly superior to first/second‐generation EGFR‐TKIs with or without chemotherapy (10.20 months vs. 4.80 months, p < 0.001; 10.20 months vs. 3.30 months, p = 0.004). The median overall survival (mOS) for patients treated with third‐generation EGFR‐TKIs and with non‐third‐generation therapy was 39.80 months (95% CI 23.14 to 56.46) and 32.40 months (95% CI 18.71 to 46.09), p = 0.408, respectively. Conclusions Third‐generation EGFR‐TKIs significantly improved mPFS in T790M‐negative patients with EGFR‐mutated advanced NSCLC and resistant to first‐line treatment with first‐ or second‐generation EGFR‐TKIs. Trial Registration ChiCTR2500096109

Background:Lung cancer, especially non-small cell lung cancer (NSCLC), is a leading cause of cancer mortality. Epidermal growth factor receptor (EGFR) mutations drive NSCLC progression but also sensitize tumors to EGFR-tyrosine kinase inhibitors (TKIs). However, the response rate to targeted therapy is only 70%, and most patients experience disease progression 9 to 14 months after first- or second-generation EGFR-TKI treatment. This study aims to examine the association between super-amplification refractory mutation system (ARMS)-derived ΔCt values [mutant DNA cycle threshold (Ct) value relative to the endogenous reference gene (Ct) value] and EGFR mutation (EGFRm) abundance in predicting the efficacy and prognosis of EGFR-TKIs in NSCLC patients. Methods:The present retrospective research encompassed 139 patients with stage IIIB-IV NSCLC treated with EGFR-TKIs. Patients were categorized based on super-ARMS ΔCt values and Kaplan-Meier, and Cox regression models were used to evaluate the outcomes in survival and independent influencing factors, thus establishing the optimal ΔCt value for EGFR-TKIs response. Results:High mutation abundance, defined by ΔCt ≤3.76, was correlated with increased objective response rate (ORR) (61.2% vs. 36.8%, P=0.003) and longer median progression-free survival (mPFS) (20.9 vs. 15.8 months, log-rank P=0.005) compared to low abundance. The optimal ΔCt cut-off predictive of EGFR-TKIs response was 4.335. Patients with ΔCt ≤4.335 demonstrated superior ORR (64.6% vs. 28.1%, P<0.001) and mPFS (20.9 vs. 13.5 months, log-rank P<0.001) compared to those with ΔCt >4.335. Multivariate Cox analysis identified median ΔCt value group (ΔCt ≤3.76 or ΔCt >3.76), the optimal ΔCt cut-off value group (ΔCt ≤4.335 or ΔCt >4.335), brain metastasis, liver metastasis, EGFRm status, performance status (PS) score, and the generation of EGFR-TKIs as independent predictors of PFS in first-line EGFR-TKIs-treated patients. Conclusions:Stratification based on ΔCt values derived from the super-ARMS system can predict the efficacy and clinical prognosis of first-line EGFR-TKI treatment in NSCLC patients. Additionally, higher mutation abundance may contribute to the superior efficacy and prognosis of EGFR-TKIs in patients with exon 19 deletions compared to those with the 21L858R mutation.

This study aims to systematically evaluate the global distribution, academic impact, and technological trends of ultrasound technology in lung cancer research from 2000 to 2024 through bibliometric analysis, providing references for future research directions. Based on the Web of Science Core Collection database, 2,617 publications from 2000 to 2024 were included. Bibliometric analysis was conducted using VOSviewer and CiteSpace, covering publication trends, countries, institutions, authors, journals, highly cited literature, and keyword co-occurrence networks. Metrics such as publication volume, citation count, and total link strength (TLS) were quantitatively assessed. From 2000 to 2024, the annual number of publications on ultrasound in lung cancer diagnosis and treatment surged from 19 to 218, with the last five years accounting for 38

ObjectiveIn treatment-naïve patients with EGFR-mutated non-small-cell lung cancer (NSCLC) complicated by malignant pleural effusion (MPE), we first investigated whether the addition of intrathoracic chemotherapy (ICT) to first-line EGFR tyrosine-kinase inhibitors (EGFR-TKIs) confers superior therapeutic efficacy or survival outcomes compared with EGFR-TKI monotherapy. Subsequently, multivariable analyses were performed to identify independent prognostic determinants across the entire cohort, thereby informing individualized treatment selection.MethodsA retrospective analysis was performed, ultimately including 169 individuals diagnosed with stage IVA-IVB NSCLC who tested positive for EGFR mutations and exhibited malignant pleural effusion at initial presentation. All patients underwent either first-line EGFR-TKI monotherapy or a combination of intrathoracic chemotherapy with EGFR-TKIs. Patients were grouped according to receipt of EGFR-TKIs with or without concomitant ICT and by pertinent clinical characteristics. Kaplan-Meier survival analysis and Cox proportional hazards regression models were utilized to evaluate survival outcomes and potential influencing factors. The study’s objective was to determine the differential impact of intrathoracic chemotherapy plus EGFR-TKIs versus EGFR-TKIs alone on therapeutic efficacy and survival, while concurrently elucidating the independent prognostic relevance of clinical characteristics in EGFR-mutated NSCLC patients presenting with malignant pleural effusion, thereby guiding treatment prioritization.ResultsAmong patients with stage IVA-IVB NSCLC who were EGFR mutation-positive and presented with malignant pleural effusion at initial diagnosis, a comparative analysis showed no statistically significant differences in median progression-free survival (mPFS) (18.2 months vs. 15.0 months, Log Rank p = 0.07) and median overall survival (mOS) (29.2 months vs. 30.6 months, Log Rank p = 0.09) between EGFR-TKI monotherapy and the combination of thoracic perfusion chemotherapy with EGFR-TKIs. Further univariate and multivariate analyses indicated that the combination of EGFR-TKIs and ICT did not significantly impact PFS or OS. However, the use of third-generation EGFR-TKIs and the presence of exon 19 deletions independently predicted longer PFS, while ECOG performance status > 1, the presence of compound mutations, and liver metastasis predicted shorter OS.ConclusionDespite our study failing to demonstrate superior efficacy or survival benefits of ICT combined with EGFR-TKIs compared to EGFR-TKI monotherapy, considering that international clinical guidelines recommend pleural drainage as a standard approach for managing MPE and the significant efficacy of third-generation EGFR-TKIs observed in our study for treating EGFR mutation-positive lung cancer patients with MPE, we speculate that the combination of third-generation EGFR-TKIs and pleural drainage may be a more rational treatment option for this patient population. Future studies are needed to further validate this hypothesis.

Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC.

目的 探讨长非编码RNA母系表达基因8(lncRNA MEG8)通过调控miR-363-3p/人类配对盒基因6(PAX6)轴促进非小细胞肺癌(NSCLC)的肿瘤进展.方法 选取 116 例经确诊为NSCLC患者的肿瘤组织与癌旁正常组织标本,常规培养人NSCLC细胞株 A549、H1299,采用 RT-qPCR 法检测组织和细胞中 lncRNA MEG8、miR-363-3p 和 PAX6 mRNA 的表达.将A549、H1299 细胞分别分为对照组(control 组,空白培养基处理)、pcDNA 组(转染 pcDNA)、pcDNA-MEG8 组(转染 pcDNA-MEG8)、pcDNA-MEG8+miR-NC组(pcDNA-MEG8 与miR-NC共转染)、pcDNA-MEG8+miR-363-3p mimic组(pcDNA-MEG8 与miR-363-3p mimic共转染).CCK-8 法检测培养24,48,72 h各组细胞增殖能力;细胞划痕实验检测细胞迁移能力;流式细胞术检测细胞凋亡;采用Western blot检测凋亡相关蛋白Bax、Bcl-2、Caspase-3 和PAX6 蛋白的表达.双荧光素酶报告基因实验分别验证MEG8 和miR-363-3p、miR-363-3p和PAX6 的关系.RNA结合蛋白免疫沉淀(RIP)实验检测lncRNA MEG8、miR-363-3p和PAX6 之间的结合.结果 与正常组织相比,肿瘤组织中lncRNA MEG8、PAX6 mRNA高表达,miR-363-3p呈现低表达(均P＜0.05).与control 组和 pcDNA 组相比,pcDNA-MEG8 组培养 48,72 h A549 和 H1299 细胞增殖能力、细胞迁移率、PAX6、Bcl-2 蛋白表达显著升高(P＜0.05),细胞凋亡率和Bax、Caspase-3 蛋白显著降低(P＜0.05).与pcDNA-MEG8 组和pcDNA-MEG8+miR-NC组相比,pcDNA-MEG8+miR-363-3 mimic组培养48,72 h A549 和H1299 细胞增殖能力、细胞迁移率、PAX6、Bcl-2 蛋白表达显著降低(P＜0.05),miR-363-3p表达、细胞凋亡率、Bax、Caspase-3 蛋白表达显著升高(P＜0.05).双荧光素酶报告基因实验结果显示,与miR-NC+MEG8-WT共转染组相比,miR-363-3p mimic+MEG8-WT共转染组荧光素酶活性显著降低(P＜0.05);与miR-NC+MEG8-MUT共转染组相比,miR-363-3p mimic+MEG8-MUT共转染组荧光素酶活性无显著差异(P＞0.05).与miR-NC+PAX6-WT共转染组相比,miR-363-3p mimic+PAX6-WT共转染组荧光素酶活性显著降低(P＜0.05);与miR-NC+PAX6-MUT共转染组相比,miR-363-3p mimic+PAX6-MUT共转染组荧光素酶活性无显著性差异(P＞0.05).RIP实验结果显示,与IgG处相比,lncRNA MEG8 和miR-363-3p、miR-363-3p和PAX6 均主要富集在Ago2 处,IgG处与Ago2 处的lncRNA MEG8、miR-363-3p和PAX6RNA相对表达水平均具有统计学差异(P＜0.05),提示lncRNA MEG8 和miR-363-3p、miR-363-3p和PAX6 能靶向结合.结论 过表达lncRNA MEG8 可能通过下调miR-363-3p并促进PAX6 蛋白的表达,进而促进NSCLC的进展.

Cervical cancer (CC) is among the leading causes of cancer-associated mortality in women worldwide; yet the molecular regulators involved in its progression are unclear. This study found that miR-182 was overexpressed in CC tissues when compared with adjacent normal tissues. Moreover, it found that miR-182 expression was significantly positively correlated with distant metastasis in patients with CC. Interestingly, in vitro experiments showed that overexpression and inhibition of miR-182 promoted and suppressed the growth of CC cells, respectively. The tumor-promoting effects of miR-182 on CC progression were achieved via the Wnt/β-catenin axis and its downstream genes. Thus, this study revealed the potential of miR-182/β-catenin as an effective new target for CC treatment.

Lung cancer has the highest morbidity rate (11.6%) and mortality rate (18.4%) among all current tumors. The morbidity rate in China accounts for approximately one-third, and it is still rising. Nonsmall cell lung cancer is the most common type of lung cancer, accounting for 80%-85% of all lung cancers, and approximately 57% of patients with advanced nonsmall cell lung cancer have distant metastases at the time of diagnosis. To explore the expression changes in microRNA-184 (miR-184) and its clinical value in serum exosomes of patients with nonsmall cell lung cancer (NSCLC). This study adopted a case-control study method, selecting 88 patients (NSCLC group) from June 2015 to June 2017 in our hospital who are confirmed to have NSCLC by fiber-optic bronchoscopy, and 90 patients who are confirmed to have benign lung diseases by pathological examination during the same period (control group). Fluorescence quantitative PCR technology is used to detect the levels of miR-184 in serum exosomes of the two groups, and the differences in the levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics are analyzed. According to the results of the 3-year follow-up, the miR-184 levels in serum exosomes of NSCLC patients are grouped and compared. The expression level of miR-184 in serum exosomes in the NSCLC group is significantly higher than that in the control group, and the difference between the two groups is statistically significant (p < 0.05). The ROC curve is drawn with the expression level of miR-184 in serum exosomes of the two groups of patients. The results showed that the area under the ROC curve for the differential diagnosis of NSCLC and benign lung tumors with the expression level of miR-184 in serum exosomes is 0.927, and the sensitivity is 87.61%, while the specificity is 84.02%. The expression levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics, in different TNM stages [(I+II) vs. (III+IV)], lymph node metastasis (yes vs. no), and different degrees of differentiation [(High + Medium) vs. Poorly differentiated] are compared and showed statistical significance (p < 0.05). In 88 NSCLC patients, after 3 years of follow-up, 33 survived, and 55 died, with a survival rate of 37.50%. The expression of miR-184 in serum exosomes of the 33 surviving patients is significantly lower than that of the nonsurviving group (p < 0.05). The expression level of miR-184 in serum exosomes of NSCLC patients is significantly increased, which has a certain value for the differential diagnosis of the nature of benign and malignant lung diseases and is closely related to the prognosis of patients.

OBJECTIVES:We aimed at investigating whether serum exosomal miR-16-5p could be utilized as an immunotherapy biomarker in lung adenocarcinoma (LUAD) patients administered by programmed cell death ligand-1 (PD-L1) inhibitors, and to evaluate its functions in LUAD progression. METHODS:Sixty LUAD sufferers and 20 healthy controls (HCs) were covered in this work. We applied both IHC and WB to examine PD-L1 level in clinical tissue samples and utilized WB to quantify PD-L1 expression in LUAD cells and LUAD xenograft tissues, respectively. Transmission electron microscopy (TEM), WB, and nanoparticle tracking analysis (NTA) were executed to confirm the exosomes isolated from serum specimens and cell culture media. To quantify of exosomal miR-16-5p level from serum and culture medium of cultured cell, qRT-PCR experiment was utilized. The connection between tissue PD-L1 level and serum exosomal miR-16-5p expression in PD-L1-positive sufferers administered by PD-L1 inhibitors was verified using Spearman correlation coefficient analysis. In addition, the overall survival (OS) and progression-free survival (PFS) rates among PD-L1 inhibitor managed sufferers were acquired through a follow-up visit. Finally, we used a group of assays, including 5-bromo-2'-dexoyuridine (BrdU) and colony formation test, wound healing experiment, flow cytometry, and nude mice xenograft experiment, to explore the functions of circulating exosomal miR-16-5p on LUAD cell proliferation, apoptosis, and migration, as well as tumor development, respectively. RESULTS:PD-L1 expression was positively related to T stage (tumor size stage), and PD-L1 inhibitor treatment reduced the PD-L1 expression and mitigated T stage in PD-L1-positive LUAD sufferers. For PD-L1-positive LUAD sufferers, elevated PD-L1 expression or reduced serum exosomal miR-16-5p level were linked to longer PFS and OS upon PD-L1 inhibitor treatment. The number of exosomes in patient's serum was more than that in the serum of healthy individuals, and PD-L1 inhibitor treatment decreased the number of serum-derived exosomes in PD-L1-positive LUAD sufferers. Exosome-derived miR-16-5p was downregulated in patient's serum and cell culture medium, and this was negatively linked to tumor stage and PD-L1 expression. Meanwhile, PD-L1 inhibitor treatment could increase the serum exosomal miR-16-5p expression, and the expression change of serum exosomal miR-16-5p was diametrically related to PD-L1 after the treatment. Moreover, the overexpression of PD-L1 accelerated tumor growth and decreased the exosomal miR-16-5p content in cell culture media, while exosomal miR-16-5p overexpression in cell culture media inhibited tumor development by decreasing the PD-L1 expression. Exosomal miR-16-5p overexpression in cell culture media also depressed LUAD cell proliferation and migration, and stimulated cell apoptosis, especially in the cells which cultured in the mediums with PD-L1 inhibitor in vitro. CONCLUSIONS:Serum exosomal miR-16-5p may be a latent tumor inhibitor and a new biomarker for PD-L1 inhibitor-dependent immunotherapy in LUAD by regulating the PD-L1 expression.

Background: The aim of the present study was to summarize the clinical and pathological characteristics of 11 non-small cell lung cancer (NSCLC) patients with mesenchymal-epithelial transition factor exon 14 Methods: From 2018 to 2021, medical records of 763 NSCLC patients were reviewed and 11 patients carrying METex14 were identified from the Affiliated Hospital of Guangdong Medical University. Their clinical data were subsequently examined for pathological and related clinical information including symptom and diagnosis, imaging and follow-up. Results: The METex14 cohort includes 9 males and 2 females and the age range was 69-85 years, with a median age of 77 years. Of the patients one is diagnosed with stage IVB lung adenosquamous carcinoma, 7 with lung adenocarcinoma (1 with stage IIIA and 6 with stage IV), and 3 with stage IV lung sarcomatoid carcinoma. 3 reached stable disease until the end of follow-up and 4 died within a year due to multiple metastases. In 4 cases, the patients received selective MET inhibitor treatment all lived longer than 7 months. There were 4 heterozygous point mutations and 1 deletion of the MET gene in this cohort, as follows: c.G3028T (p.D1010Y); c.G3028A (p.D1010N); c.G3005C (p.V1002A); c.3022C>G and MET c.3021_3028+20del (E14). Conclusions: According to the data that we collected, the incidence of NSCLC carrying METex14 is low and male outnumber female in our sample pool. Selective target therapy had better prognosis than multitargeted tyrosine kinase inhibitor (TKI) such as crizotinib or standard therapy.

The current study aimed to investigate the function of the Hedgehog pathway and its association with epithelial-mesenchymal transition (EMT) in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). Lung tumor tissue specimens from EGFR TKI-resistant patients, including those with brain metastases, had hyperactive Hedgehog signaling compared with those from TKI-sensitive patients. SHH stimulation promoted GLI1 activation as well as cell motility in parental PC9 cells while suppressing gefitinib-induced apoptosis in gefitinib-resistant cells. SHH also promoted EMT in parental PC9 cells via E-cadherin suppression and N-cadherin and vimentin upregulation. The knockdown of GLI1 exhibited the opposite effects. Besides, SHH induced, whereas GLI1 knockdown reversed gefitinib resistance in xenograft tumors. The Hedgehog pathway inhibitor GDC-0449 synergized with gefitinib to increase xenograft tumor sensitivity to chemotherapy and extend survival in tumor-bearing animals. These results suggest the Hedgehog pathway mediates EGFR TKI resistance and induces EMT in NSCLC, representing a potential therapeutic target to defeat TKI resistance.

Lung cancer has the highest morbidity rate (11.6%) and mortality rate (18.4%) among all current tumors. The morbidity rate in China accounts for approximately one-third, and it is still rising. Nonsmall cell lung cancer is the most common type of lung cancer, accounting for 80%–85% of all lung cancers, and approximately 57% of patients with advanced nonsmall cell lung cancer have distant metastases at the time of diagnosis. To explore the expression changes in microRNA-184 (miR-184) and its clinical value in serum exosomes of patients with nonsmall cell lung cancer (NSCLC). This study adopted a case-control study method, selecting 88 patients (NSCLC group) from June 2015 to June 2017 in our hospital who are confirmed to have NSCLC by fiber-optic bronchoscopy, and 90 patients who are confirmed to have benign lung diseases by pathological examination during the same period (control group). Fluorescence quantitative PCR technology is used to detect the levels of miR-184 in serum exosomes of the two groups, and the differences in the levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics are analyzed. According to the results of the 3-year follow-up, the miR-184 levels in serum exosomes of NSCLC patients are grouped and compared. The expression level of miR-184 in serum exosomes in the NSCLC group is significantly higher than that in the control group, and the difference between the two groups is statistically significant ( p  < 0.05). The ROC curve is drawn with the expression level of miR-184 in serum exosomes of the two groups of patients. The results showed that the area under the ROC curve for the differential diagnosis of NSCLC and benign lung tumors with the expression level of miR-184 in serum exosomes is 0.927, and the sensitivity is 87.61%, while the specificity is 84.02%. The expression levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics, in different TNM stages [(I+II) vs. (III+IV)], lymph node metastasis (yes vs. no), and different degrees of differentiation [(High + Medium) vs. Poorly differentiated] are compared and showed statistical significance ( p  < 0.05). In 88 NSCLC patients, after 3 years of follow-up, 33 survived, and 55 died, with a survival rate of 37.50%. The expression of miR-184 in serum exosomes of the 33 surviving patients is significantly lower than that of the nonsurviving group ( p  < 0.05). The expression level of miR-184 in serum exosomes of NSCLC patients is significantly increased, which has a certain value for the differential diagnosis of the nature of benign and malignant lung diseases and is closely related to the prognosis of patients.

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.

Lung cancer has the highest morbidity rate (11.6%) and mortality rate (18.4%) among all current tumors. -e morbidity rate in China accounts for approximately one-third, and it is still rising. Nonsmall cell lung cancer is the most common type of lung cancer, accounting for 80%–85% of all lung cancers, and approximately 57% of patients with advanced nonsmall cell lung cancer have distant metastases at the time of diagnosis. To explore the expression changes in microRNA-184 (miR-184) and its clinical value in serum exosomes of patients with nonsmall cell lung cancer (NSCLC). -is study adopted a case-control study method, selecting 88 patients (NSCLC group) from June 2015 to June 2017 in our hospital who are confirmed to have NSCLC by fiber-optic bronchoscopy, and 90 patients who are confirmed to have benign lung diseases by pathological examination during the same period (control group). Fluorescence quantitative PCR technology is used to detect the levels of miR-184 in serum exosomes of the two groups, and the differences in the levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics are analyzed. According to the results of the 3-year follow-up, the miR-184 levels in serum exosomes of NSCLC patients are grouped and compared. -e expression level of miR-184 in serum exosomes in the NSCLC group is significantly higher than that in the control group, and the difference between the two groups is statistically significant (p< 0.05). -e ROC curve is drawn with the expression level of miR-184 in serum exosomes of the two groups of patients. -e results showed that the area under the ROC curve for the differential diagnosis of NSCLC and benign lung tumors with the expression level of miR-184 in serum exosomes is 0.927, and the sensitivity is 87.61%, while the specificity is 84.02%. -e expression levels of miR-184 in serum exosomes of NSCLC patients with different pathological characteristics, in different TNM stages [(I+II) vs. (III+IV)], lymph node metastasis (yes vs. no), and different degrees of differentiation [(High +Medium) vs. Poorly differentiated] are compared and showed statistical significance (p< 0.05). In 88 NSCLC patients, after 3 years of follow-up, 33 survived, and 55 died, with a survival rate of 37.50%. -e expression of miR-184 in serum exosomes of the 33 surviving patients is significantly lower than that of the nonsurviving group (p< 0.05). -e expression level of miR-184 in serum exosomes of NSCLC patients is significantly increased, which has a certain value for the differential diagnosis of the nature of benign and malignant lung diseases and is closely related to the prognosis of patients.

目的:对hsa-miR-497进行靶基因和功能生物信息学分析预测,为后续深入研究其生物学功能和调控机制提供实验理论指导,并对其在肺腺癌中的表达进行初步验证.方法:利用PubMed检索miR-497相关文章,通过miRBase在线工具分析miR-497碱基序列、染色体定位等信息.应用Targetscan及miRDB两种预测工具对miR-497进行靶基因预测取其交集,应用R中clusterProfiler包进行靶基因功能富集及信号转导通路富集分析.最后应用RT-PCR定量检测miR-497在新鲜肺腺癌及癌旁组织中的表达.结果:miR-497在多物种间具有高度的保守性,功能富集分析预测的结果显示miR-497调控的靶基因集合功能主要富集于输尿管芽生长、穿膜受体蛋白激酶、肽结合、分支形态发生和膜筏等过程(P<0.05).KEGG生物通路显著富集于调控干细胞多能性、癌、Wnt及Rap1信号通路等(P<0.001).miR-497在肺腺癌组织中表达明显低于癌旁组织,差异有统计学意义(P<0.05).结论:miR-497通过靶基因调控多个生物学过程及疾病通路,尤其在肿瘤方向的生物学功能值得进一步研究,miR-497在肺腺癌中低表达为研究肺腺癌的发生及发展及治疗提供了新的方向.

目的 比较序贯放化疗与同步放化疗对ⅢA-N2期非小细胞肺癌的治疗效果.方法 将40例ⅢA-N2期非小细胞肺癌患者按照随机数字表法分为序贯组(接受化疗序贯纵隔淋巴结放疗)与同步组(接受化疗同步纵隔淋巴结放疗),每组20例.比较两组患者的临床疗效、治疗前后的血清肿瘤标志物[糖类抗原125(CA125)、鳞状上皮细胞癌抗原(SCC-Ag)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)]水平、治疗期间不良反应发生情况、无进展生存时间(PFS)和总生存时间(OS).结果 同步组患者的总有效率为75％(15/20),高于序贯组患者的35％(7/20),差异有统计学意义(P<0.05).同步组患者的临床疗效优于序贯组患者,差异有统计学意义(P<0.05).治疗后,同步组患者血清中的CEA、CYFRA21-1、SCC-Ag水平均低于序贯组患者,差异均有统计学意义(P<0.05).两组患者的各不良反应发生率比较,差异均无统计学意义(P>0.05).同步组患者的PFS、OS均长于序贯组患者,差异均有统计学意义(P<0.05).结论 与序贯放化疗相比,同步放化疗对于IIIA-N2期非小细胞肺癌患者的临床疗效更优,能够有效延长患者的生存时间,且不会增加不良反应.

目的 探讨胸部放疗剂量对诱导化疗后未进展ES-SCLC患者临床预后的影响.方法 回顾性分析我院2010年1月-2015年12月收治诱导化疗后未进展ES-SCLC患者共108例临床资料,其中18例单纯接受化疗,90例则加用胸部放疗;同时根据放疗剂量进行分组,比较不同组,中位总生存时间和无进展生存时间,采用Cox回归模型分析临床预后影响因素.结果 :①放疗组患者中位总生存时间和无进展生存时间显著长于化疗组(P<0.05);②放疗B组,中位总生存时间显著长于化疗组(P<0.05);放疗C组和放疗D组总生存时间和无进展生存时间均显著长于放疗A组、放疗B组、化疗组(P<0.05);③单因素分析结果 显示,同步放化疗、肝或骨转移、病灶转移数量及放疗剂量,是患者总生存时间预后影响因素(P<0.05);同时病灶转移数目和放疗剂量是患者无进展生存时间预后影响因素(P<0.05).Cox回归模型分析结果 显示,同步放化疗、病灶转移数量及放疗剂量是患者总生存时间预后独立影响因素(P<0.05);病灶转移数量和放疗剂量是患者无进展时间独立影响因素(P<0.05);④倾向性评分匹配因素包括年龄、吸烟、KPS评分、体重减轻,转移灶个数、转移器官个数、脑转移、肝骨转移、同步放化疗、放疗时机、分割方式及脑预防;倾向性评分匹配分析结果 显示,高剂量放疗患者中位总生存时间和无进展生存时间均显著长于低剂量放疗患者(P<0.05).结论 诱导化疗后未进展ES-SCLC患者加用胸部放疗有助于改善临床预后,同时给予49.5～53.7Gy放疗剂量在延长生存时间方面更具优势,在此基础上增加或减少放疗剂量均未明显增加生存获益.