Search

Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator, and is associated with the malignant progression of lung cancer. However, the mechanisms of EZH2 on lung adenocarcinoma (LUAD) remain unclear. The relationship between EZH2 and SPOCK2 or SPRED1 was confirmed by dual-luciferase reporter assay. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to examine the expression of SPOCK2 and SPRED1 and their prognostic values of LUAD. The effects of SPOCK2 and SPRED1 on the biological characters of LUAD cells were identified on functional assays in vitro and in vivo. Our results showed that EZH2 suppressed the expression and transcriptional activity of SPOCK2 and SPRED1, and these effects were reversed by the EZH2 inhibitor, Tazemetostat. SPOCK2 and SPRED1 were expressed at low levels in LUAD patients, and a high expression level of SPOCK2 or SPRED1 predicted better survival. Moreover, overexpression of SPOCK2 or SPRED1 could inhibit tumoral proliferation, migration ratio, and invasion activity in vitro as well as retard tumor growth in vivo. However, EZH2 elevation could rescue these impacts and accelerate LUAD progression. Our findings reveal that SPOCK2 and SPRED1 are epigenetically suppressed by EZH2 and may act as novel regulators to inhibit the proliferation, migration, and invasion of LUAD cells. [ABSTRACT FROM AUTHOR]

Background. Lymph node metastasis (LNM) is the main route of metastasis in lung adenocarcinoma (LA), and preoperative prediction of LNM in early LA is key for accurate medical treatment. We aimed to establish a preoperative prediction model of LNM of early LA through clinical data mining to reduce unnecessary lymph node dissection, reduce surgical injury, and shorten the operation time. Methods. We retrospectively collected imaging data and clinical features of 1121 patients with early LA who underwent video-assisted thoracic surgery at the First Hospital of China Medical University from 2004 to 2021. Logistic regression analysis was used to select variables and establish the preoperative diagnosis model using random forest classifier (RFC). The prediction results from the test set were used to evaluate the prediction performance of the model. Results. Combining the results of logistic analysis and practical clinical application experience, nine clinical features were included. In the random forest classifier model, when the number of nodes was three and the n -tree value is 500, we obtained the best prediction model (accuracy = 0.9769), with a positive prediction rate of 90% and a negative prediction rate of 98.69%. Conclusion. We established a preoperative prediction model for LNM of early LA using a machine learning random forest method combined with clinical and imaging features. More excellent predictors may be obtained by refining imaging features. [ABSTRACT FROM AUTHOR]

Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achieved a complete response to subsequent immune checkpoint inhibitor (ICI) therapy. The concentration of circulating tumor DNA (ctDNA) following the treatment course strongly reflects the response to ICI therapy. This report highlights the efficacy of ICI treatment in metastatic LCNELC patients with a high TMB and suggests that ctDNA analysis in detecting molecular residual disease may facilitate the personalization of ICI therapy. [ABSTRACT FROM AUTHOR]

The progression of lung adenocarcinoma through lymph node metastasis has been well established; however, the process of segmental lymph node (LSN) metastasis in cT1N0M0 lung adenocarcinoma remains unclear. We aimed to elucidate the markers of lymph node metastasis to different segments in early-stage lung adenocarcinoma and identify new indications for segmentectomy. A total of 200 patients were enrolled in this study. These patients were diagnosed with cT1N0M0 lung adenocarcinoma after positron emission tomography/computed tomography and received lobectomy and lymph node dissection surgeries. Lymph nodes retrieved from each station were sorted. The metastatic status of the isolated (i) LSNs and several characteristics were analyzed. Patients with ground-glass nodules (GGNs) (P = 0.025), AIS/MIA/lepidic adenocarcinoma (P = 0.038), nodules with a maximum diameter ≤1 cm (P = 0.017), maximum standardized uptake value (SUVmax) < 2.5 (P = 0.029), serum carcinoembryonic antigen (CEA) levels ≤4.5 ng/ml (P = 0.036), and no N1 lymph nodes metastasis (P = 0.036) had significantly lower iLSN metastasis rates than those without these characteristics. Pure GGNs, CEA levels ≤4.5 ng/ml, SUVmax < 2.5, tumors with a maximum diameter of ≤1 cm, or those confirmed to be adenocarcinoma in situ, minimally invasive adenocarcinoma, or invasive lepidic-predominant adenocarcinoma by frozen section may indicate segmentectomy. However, segmentectomy is not suitable for patients with metastasis to the N1 lymph nodes. [ABSTRACT FROM AUTHOR]

MicroRNA‐198‐5p (miR‐198‐5p) displays crucial roles in various cancers including non‐small cell lung cancer (NSCLC), but the underlying molecular mechanisms remain unclear. Fucosyltransferase 8 (FUT8) is associated with tumour metastasis and prognosis. In this study, we explored the expression of miR‐198‐5p and FUT8 in NSCLC patients. Results showed that miR‐198‐5p was under‐expressed in NSCLC tissues and was negatively correlated with tumour size, lymph node metastasis and tumour‐node‐metastasis stage, while FUT8 expression was highly upregulated. Next, we altered miR‐198‐5p expression using the mimic or inhibitor in the functional study. Results showed that miR‐198‐5p overexpression could inhibit the migration, invasion and epithelial‐to‐mesenchymal transition (EMT) of NSCLC cells; reversely, suppression of miR‐198‐5p enhanced cell migration, invasion and EMT. In vivo, miR‐198‐5p overexpression inhibited the formation of mouse lung and liver metastasis. Luciferase reporter, real‐time PCR and western blot assays showed that miR‐198‐5p could directly target FUT8 and regulate FUT8 expression. Further, FUT8 overexpression reversed the effect of miR‐198‐5p overexpression on the migration, invasion and EMT of NSCLC cells. Taken together, miR‐198‐5p functions as a tumour suppressor by targeting FUT8 in NSCLC. MiR‐198‐5p may be developed as a new diagnostic biomarker and therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite encouraging results achieved with targeted therapy in recent years, the early diagnosis and treatment of lung cancer remains a major problem. Circular RNA (circRNA), a type of RNA with covalently closed continuous loop structures, has structural stability and certain tissue specificity. Recent studies have found that circRNAs have an important role in tumor development and are expected to be revealed as new targets for tumor prediction and treatment. Research on the biological functions and regulation mechanisms of circRNAs in lung cancer is in its infancy but is gathering momentum. In this review, we discuss the properties, biogenesis, biological function, and research progress of circRNAs in lung cancer to provide a theoretical foundation and new directions for studies on circRNAs in lung cancer. [ABSTRACT FROM AUTHOR]

Abstract CircRNAs are reported to be implicated in the development of lung cancer. This study focused on assessing the expression, functions and molecular mechanism of circPUM1 in lung adenocarcinoma. Here, it showed that circPUM1 is significantly upregulated in both lung adenocarcinoma cell lines and tissues. Furthermore, silencing of circPUM1 impaired the proliferation, migration and invasion ability, and increased apoptosis in A549 cells. Nevertheless, overexpression of circPUM1 in SPC-A1 cells has the opposite effect. Silencing of circPUM1 inhibits the tumorigenesis in nude mice. Mechanistically, circPUM1 could sponge miR-326 and promote the expression of its downstream proteins Cyclin D1 and Bcl-2. In summary, this present study revealed that circPUM1 functions as an oncogene to promote the tumorigenesis of lung adenocarcinoma through circPUM1/miR-326/Cyclin D1 and Bcl-2 axis. This indicates that circPUM1 may act as a potential therapeutic target for lung adenocarcinoma. Highlights • Upregulation of circPUM1 in lung adenocarcinoma cell lines and tissues. • Silencing of circPUM1 inhibits the proliferation, migration, invasion and inhibited apoptosis in vitro, and vice versa. • CircPUM1 sponges miR-326 to upregulate Cyclin D1 and Bcl-2 expression to promote tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is one of the major types of lung cancer, which is a prevalent human disease all over the world. LncRNA LINC01503 is a super-enhancer-driven long non-coding RNA that is dysregulated in several types of human cancer. However, its role in NSCLC remains unknown.Methods: Thirty NSCLC patients were recruited between April 2012 and April 2016. Luciferase reporter assay, qRT-PCR, Cell Counting Kit-8 (CCK-8), Transwell migration assay, RNA pull-down assay, western blotting, 5-ethynyl-29-deoxyuridine (EdU) assays, and flow cytometry were utilized to characterize the roles and relationships among LINC01503, miR-342-3p, and LASP1 in NSCLC. The transplanted mouse model was built to examine their biological functions in vivo.Results: We demonstrated that the expression of lncRNA LINC01503 and LIM and SH3 domain protein 1 (LASP1) were upregulated and miR-342-3p was downregulated in NSCLC samples and cell lines. Functional experiments revealed that inhibiting the expression of LINC01503 or over-expression of miR-342-3p inhibited NSCLC growth and metastasis both in vitro and in vivo. In addition, LINC01503 could bind to miR-342-3p and affect the expression of LASP1.Conclusion: These results provide a comprehensive analysis of the roles of LINC01503 as a competing endogenous RNA (ceRNA) in NSCLC progression. [ABSTRACT FROM AUTHOR]

Background: We present a critical comparison of lobectomy and sub-lobar resection in elderly patients with early stage non-small cell lung cancer using meta-analytical techniques.Methods: A literature search was conducted between the period of December 1997 to March 2019 to identify the comparative studies evaluating 1-, 3-, and 5-year survival rates. The pooled odds ratios (OR) and the 95% confidence intervals (95% CI) were calculated with either the fixed or random effect models, respectively.Results: Six retrospective studies are included in our meta-analysis for a total of 1205 patients. 843 of the individuals were treated with lobectomy, while 362 were treated with sub-lobar resection. We found no significant difference between the lobectomy and the sub-lobar resection in either of the 1-, 3-, or 5-year survival rates.Conclusions: This study suggests that in elderly individuals with stage I NSCLC, a sub-lobar resection is statistically equivalent to the lobectomy in terms of 1-, 3-, and 5-year survival rates. Further large-scale randomized studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC.Methods: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079.Findings: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related.Interpretation: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature.Funding: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China. [ABSTRACT FROM AUTHOR]

Nanoparticles are efficient delivery vehicles for cancer therapy such as paclitaxel (PTX). In this study, we formulated PTX into PLGA polymeric nanoparticles. Vitamin E TPGS was used as an emulsifier to stabilize the nanoparticle formulation. PTX was encapsulated in TPGS-emulsified polymeric nanoparticles (TENPs) by a nanoprecipitation method in ethanol–water system. The resultant PTX-TENPs showed a very uniform particle size (∼100 nm) and high drug encapsulation (>80%). The cytotoxicity of PTX-TENPs was examined in A549 lung cancer cell line. Preferential tumor accumulation of TENPs was observed in the A549 lung cancer xenograft model. Tumor growth was significantly inhibited by intravenous injection of PTX-TENPs. Our results suggested that the modified nanoprecipitation method holds great potential for the fabrication of the PTX loaded polymeric nanoparticles. TPGS can be used in the manufacture of polymeric nanoparticles for the controlled release of PTX and other anti-cancer drugs. [ABSTRACT FROM AUTHOR]