Concordance of ctDNA and tissue mutations in NSCLC: A meta-analysis.

Systematic evaluation of the consistency between circulating tumor DNA (ctDNA) in plasma and tumor tissue samples in mutations in non-small cell lung cancer (NSCLC) patients. To collect publicly published literature from numerous important international medical databases through computer retrieval. To compare the differences in literature data related to gene mutations between plasma ctDNA and tumor tissue samples, a meta-analysis was performed using Stata 12.0 software while taking into account the inclusion and exclusion criteria. This article includes a total of 15 research data and collected data reports from 15 groups of NSCLC patients. The results are displayed using tissue samples as the gold standard. The Pearson correlation coefficients of sensitivity and specificity were used to calculate rho=0.044, and P=0.893. The Q-test found poor homogeneity and high heterogeneity in sensitivity and specificity among research data from various literature studies (I2>50%, P<0.1). The area under the SROC curve is 0.97 (95% CI: 0.96~0.99). The small sample subgroup has high heterogeneity, and the combined diagnosis effect size is 26[6~111], lower than the large sample subgroup 185320 [0~2.7×1012]. When taking 200 as the cut-off point, the combined effect size of the small sample subgroup is 46 [12~183], still lower than that of the large sample subgroup 429 [52~3574]. From this, it can be concluded that the consistency of small-sample studies is higher than the quality of large-sample studies, and the heterogeneity is relatively low. From the perspective of mutation types, the heterogeneity of literature with EGFR gene mutations alone is higher than that of literature with non-EGFR mutations alone, and the consistency is lower. The consistency of using plasma ctDNA to detect mutations in NSCLC patients with tumor tissue samples is influenced by the type of mutation gene and sample size measured by the patient, and there is a significant bias in related studies.

Spectrum of germline mutations in RB1 in Chinese patients with retinoblastoma: Application of targeted next-generation sequencing.

Purpose: Retinoblastoma (RB) is a pediatric ocular malignancy due to biallelic inactivation of the RB1 gene. Genetic testing is critically important for treatment decisions for this disease. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for discovering all types of mutations in the RB1 gene. The aim of this study is the application of targeted NGS in a cohort of Chinese patients with retinoblastoma to identify germline mutations in the RB1 gene. Methods: Blood samples were collected from 149 unrelated probands with retinoblastoma (62 bilaterally and 87 unilaterally) and their parent(s). Genomic DNA was analyzed with custom panel-based targeted NGS, and the panel was designed to include exons 1-27 of the RB1 gene with flanking intronic sequences. Single nucleotide variations (SNVs) and small insertions/deletions (InDels) identified were confirmed with Sanger sequencing. If the Sanger sequencing of a low-frequency variant (LFV) detected with targeted NGS was negative, PCR-based deep NGS was conducted for added confirmation. Copy number variations (CNVs) detected with targeted NGS were confirmed with multiplex ligation-dependent probe amplification (MLPA). Results: Overall, 74 germline mutations were detected in 48.3% of the probands (72/149, 56 bilateral and 16 unilateral cases). The total detection rate in the bilateral cases was 90.3% (56/62). These mutations included 64 SNVs and InDels (25 nonsense, 20 splicing, ten frameshift, eight missense, and one synonymous variants) and ten CNVs. All CNVs were confirmed with MLPA. Twenty-four (32.4%, 24/74) variants detected were novel, including nine splicing, six frameshift, five missense, and four nonsense variants. Eight LFVs (10.8%, 8/74) were found with targeted NGS; six of which were identified with Sanger sequencing, and two were identified with PCR-based deep NGS (13.16% and 3.000% mutant rates, respectively). Conclusions: This study expanded the spectrum of germline mutations in RB1 using targeted NGS technology, which is a cost-saving and efficient method for genetic sequencing of retinoblastoma and may improve the molecular diagnosis of retinoblastoma.

Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK).

BACKGROUND: MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of cancers including esophageal carcinoma (ESCA). Increasing numbers of miRNAs have been identified to be important regulators in the progression of ESCA by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in ESCA need sufficient elucidation. AIMS: In the present study, the function of miR-2053 was investigated in ESCA cells. METHODS: The expression of miR-2053 was detected in four different ESCA cell lines (Eca109, Ec9706, KYSE30, and TE-1 cells) and normal cell line (HEEC) by qRT-PCR. Cell proliferation, migration, and invasion abilities after knockdown of miR-2053 were assessed by CCK-8 assay, scratch assay, and transwell assay, respectively. Cell cycle of ESCA cells was detected by flow cytometric analysis. Expression of proteins in ESCA cells was detected by Western blot analysis. RESULTS: The results showed that the expression of miR-2053 was remarkably up-regulated in ESCA tissues and cells lines. Down-regulation of miR-2053 markedly inhibited cell proliferation, migration, and invasion and markedly induced cell cycle arrest and cell apoptosis in ESCA cell lines. Fyn-related kinase (FRK) was a target gene of miR-2053. Moreover, down-regulation of miR-2053 mediated the protein kinase B (AKT)/mammalian target of rapamycin and Wnt3a/ß-catenin signaling pathway in ESCA cell lines. CONCLUSIONS: Our results together suggest the potential of regulating miR-2053 expression against development and progression of esophageal carcinoma by targeting FRK.

LncRNA WTAPP1 promotes cancer cell invasion and migration in NSCLC by downregulating lncRNA HAND2-AS1.

BACKGROUND: Long non-coding RNA (lncRNA) Wilms Tumor 1 Associated Protein Pseudogene 1 (WTAPP1) has been reported to be a critical player in the angiogenesis and migration of endothelial progenitor cells, while its involvement in cancer biology remains unknown. This study was carried out to investigate the role of WTAPP1 in non-small cell lung cancer (NSCLC). METHODS: The expression of WTAPP1 and lncRNA HAND2 Antisense RNA 1 (HAND2-AS1) in plasma and tissues from NSCLC patients was detected by qRT-PCR. A 5-year follow-up study was carried out to explore the prognostic value of WTAPP1 for NSCLC. Overexpression experiments were performed to analyze the interaction between WTAPP1 and HAND2-AS1. Cell invasion and migration were evaluated by Transwell assays. RESULTS: The expression of WTAPP1 was upregulated in NSCLC. The survival analysis showed that low plasma levels of WTAPP1 were accompanied with high survival rate. HAND2-AS1 was downregulated in NSCLC and inversely correlated with WTAPP1 across tumor tissues. Overexpression of WTAPP1 resulted in downregulation of HAND2-AS1 in NSCLC cells, while overexpression of HAND2-AS1 did not affect the expression of WTAPP1. Overexpression of WTAPP1 led to promoted, while overexpression of HAND2-AS1 resulted in inhibited invasion and migration of NSCLC cells. In addition, overexpression of HAND2-AS1 partially attenuated the effects of overexpressing WTAPP1. In addition, WTAPP1 did not affect cancer cell proliferation. CONCLUSION: WTAPP1 may promote cancer cell invasion and migration in NSCLC by downregulating lncRNA HAND2-AS1.

LncRNA-IUR up-regulates PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in esophageal squamous cell carcinoma.

BACKGROUNDS: Imatinib-up-regulated lncRNA (lncRNA-IUR) is a recently identified tumor suppressor, while its role in ESCC is unknown. This study aimed to investigate the role of lncRNA-IUR in esophageal squamous cell carcinoma (ESCC). METHODS: Between April 2011 and April 2014, the Second Hospital of Jilin University admitted a total of 98 ESCC patients, from whom the present study selected 50 cases (33 males and 17 females; 43-67 years; 54.8 ± 6.0 year). ESCC cells and transient transfections, qPCR, RNA interaction analysis, western blot, CCK-8 assay, and cell apoptosis analysis were applied. RESULTS: We found that IUR was down-regulated in ESCC, and low levels of IUR predicted poor survival of ESCC patients. In ESCC cells, IUR expression levels were significantly and positively correlated with PTEN mRNA. Bioinformatics analysis showed that IUR may sponge miR-21, which can target PTEN. In ESCC cells, IUR over-expression led to the increased expression levels of PTEN; while miR-21 over-expression led to decreased expression levels of PTEN. IUR and miR-21 failed to affect each other. Cell proliferation and apoptosis analysis showed that IUR and PTEN over-expression inhibited cancer cell proliferation and promoted apoptosis; while miR-21 over-expression played an opposite role. In addition, miR-21 over-expression attenuated the effects of IUR over-expression on PTEN expression and cell proliferation. CONCLUSION: Therefore, IUR may up-regulate PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in ESCC.

LncRNA Erbb4-IR promotes esophageal squamous cell carcinoma (ESCC) by downregulating miR-145.

Erbb4-IR is a recently identified lncRNA with pivotal functions in renal injury. The present study investigated the roles of Erbb4-IR in esophageal squamous cell carcinoma (ESCC). It was observed that Erbb4-IR was upregulated in tumor tissues of patients with ESCC. Plasma levels of Erbb4-IR in patients with ESCC were positively correlated with expression levels of Erbb4-IR in tumor tissues. MicroRNA-145 (miR-145) was downregulated in tumor tissues and inversely correlated with Erbb4-IR only in tumor tissues. Erbb4-IR overexpression led to downregulated miR-145, and increased rates of ECSS cell proliferation and decreased rates of ECSS cell apoptosis. Overexpression of miR-145 showed no significant effects on Erbb4-IR expression, but played an opposite role on cancer cell proliferation and apoptosis. In addition, miR-145 overexpression attenuated the effects of Erbb4-IR overexpression. Therefore, lncRNA Erbb4-IR may promote ESCC by downregulating miR-145.

Reduction of circular RNA expression associated with human retinoblastoma.

This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). Twelve paired primary samples from un-treated RB patients (primary RB samples and corresponding adjacent normal retinal samples) and eight recurrent RB samples from RB patients having recurrence after treatment were collected. Ribosomal-RNA depleted sequencing was performed in four paired primary samples. Quantitative polymerase chain reaction was conducted to validate circRNA and mRNA expression in the other eight paired primary samples and in eight recurrent RB samples. Bioinformatic analysis was applied to predict the oncological signal pathways and the binding microRNA (miRNA) of circRNA. As a result, a total of 47640 circRNAs were identified by RNA-sequencing, with a lower abundance of circRNAs in primary RB samples relative to matched normal retinal samples [22366 (47%) versus 37161 (78%), P <0.001]. Among the 11887 overlapping circRNAs in both RB and normal retinal samples, 550 circRNAs were downregulated and seven were upregulated in primary RB samples compared to normal retinal samples. The host genes of the differentially expressed circRNAs were associated with chromatin modification. TET1-has_circ_0093996 (ten-eleven translocation-1), whose host gene TET1 participates in chromatin modifying, was downregulated in both primary and recurrent RB samples. Programmed cell death 4 （PDCD4) was also downregulated in both primary and recurrent RB samples. We used bioinformatic tools to construct a complete regulatory axis including TET1-has_circ_0093996-miR-183-PDCD4 that regulates RB pathogenesis. In conclusion, circRNA expression is downregulated in RB tumor, which suggests epigenetic regulation of RB pathogenesis by circRNAs.

Isoalantolactone induces apoptosis through reactive oxygen species-dependent upregulation of death receptor 5 in human esophageal cancer cells.

Esophageal cancer is the eighth most prevalent cancer and has high mortality in our society. Isoalantolactone, extracted from Inula helenium L, has shown potent anticancer effects on a variety of cancers. However, its effect on human esophageal cancer, and the underlying molecular mechanism, remain to be investigated. In the present study, we demonstrated that isoalantolactone induced apoptosis in esophageal cancer cells. Treatment with isoalantolactone activated caspases-3, -7, and -10, and upregulated death receptor (DR)5. Furthermore, DR5 knockdown partially reversed the effect of isoalantolactone. These results indicated the extrinsic apoptosis was induced by isoalantolactone. In addition, intracellular reactive oxygen species (ROS) were significantly elevated after treatment with isoalantolactone. N-Acetylcysteine, an ROS scavenger, blocked both the apoptosis and decreased cell viability caused by isoalantolactone. In vivo, significant suppression of tumor growth by isoalantolactone was observed in an ECA109 cell xenograft mouse model. Isoalantolactone showed no obvious adverse effects on mouse weight and histology of heart, liver, spleen, lung, and kidney. In conclusion, our results revealed that isoalantolactone induced apoptosis through the extrinsic pathway via upregulation of DR5 and elevation of ROS in human esophageal cancer cells. Isoalantolactone, therefore, could be a potential candidate in developing anticancer agents for esophageal cancer patients.

Costunolide Induces Apoptosis through Generation of ROS and Activation of P53 in Human Esophageal Cancer Eca-109 Cells.

Costunolide is a sesquiterpene lactone, which possesses potent anti-cancer properties. However, there is little report about its effects on esophageal cancer. In our study, we investigated the effects of costunolide on the cell viability, cell cycle, and apoptosis in human esophageal cancer Eca-109 cells. It was found that costunolide inhibited the growth of Eca-109 cells in a dose-dependent manner, which was associated with the loss of mitochondrial membrane potential (Δψm ) and the production of ROS. Costunolide induced apoptosis of Eca-109 cells as well as cell cycle arrest in G1/S phase by upregulation of P53 and P21. Costunolide triggered apoptosis in esophageal cancer cells via the upregulation of Bax, downregulation of Bcl-2, and significant activation of caspase-3 and poly ADP-ribose polymerase. These effects were markedly abrogated when cells were pretreated with N-acetylcysteine, a specific reactive oxygen specie inhibitor. These results suggest that costunolide is a potential candidate for the treatment of esophageal cancer.

Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells.

Cepharanthine is a medicinal plant-derived natural compound which possesses potent anti-cancer properties. However, there is little report about its effects on lung cancer cells. In this study, we investigated the effects of cepharanthine on the cell viability and apoptosis in human non-small-cell lung cancer H1299 and A549 cells. It was found that cepharanthine inhibited the growth of H1299 and A549 cells in a dose-dependent manner which was associated with the generation of reactive oxygen species(ROS) and the dissipation of mitochondrial membrane potential (Δψm). These effects were markedly abrogated when cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, indicating that the apoptosis-inducing effect of cepharanthine in lung cancer cells was mediated by ROS. In addition, cepharanthine triggered apoptosis in non-small lung cancer cells via the upregulation of Bax, downregulation of Bcl-2 and significant activation of caspase-3 and PARP. These results provide the rationale for further research and preclinical investigation of cepharanthine's anti-tumor effect against human non-small-cell lung cancer.

Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases.

Macrophages, the predominant immune cells in the lungs, play a pivotal role in maintaining the delicate balance of the pulmonary immune microenvironment. However, in chronic inflammatory lung diseases and lung cancer, macrophage phenotypes undergo distinct transitions, with M1-predominant macrophages promoting inflammatory damage and M2-predominant macrophages fostering cancer progression. Exosomes, as critical mediators of intercellular signaling and substance exchange, participate in pathological reshaping of macrophages during development of pulmonary inflammatory diseases and lung cancer. Specifically, in inflammatory lung diseases, exosomes promote the pro-inflammatory phenotype of macrophages, suppress the anti-inflammatory phenotype, and subsequently, exosomes released by reshaped macrophages further exacerbate inflammatory damage. In cancer, exosomes promote pro-tumor tumor-associated macrophages (TAMs); inhibit anti-tumor TAMs; and exosomes released by TAMs further enhance tumor proliferation, metastasis, and resistance to chemotherapy. Simultaneously, exosomes exhibit a dual role, holding the potential to transmit immune-modulating molecules and load therapeutic agents and offering prospects for restoring immune dysregulation in macrophages during chronic inflammatory lung diseases and lung cancer. In chronic inflammatory lung diseases, this is manifested by exosomes reshaping anti-inflammatory macrophages, inhibiting pro-inflammatory macrophages, and alleviating inflammatory damage post-reshaping. In lung cancer, exosomes reshape anti-tumor macrophages, inhibit pro-tumor macrophages, and reshaped macrophages secrete exosomes that suppress lung cancer development. Looking ahead, efficient and targeted exosome-based therapies may emerge as a promising direction for treatment of pulmonary diseases.

Robust anti-tumor immunity through the integration of targeted lipid nanoparticle-based mRNA nanovaccines with PD-1/PD-L1 blockade.

Tumor mRNA vaccines present a personalized approach in cancer immunotherapy, encoding distinct tumor antigens to evoke robust immune responses and offering the potential against emerging tumor variants. Despite this, the clinical advancement of tumor mRNA vaccines has been hampered by their limited delivery capacity and inefficient activation of antigen-presenting cells (APCs). Herein, we employed microfluidics technology to engineer mannose-modified lipid-based nanovaccines for specifically targeting APCs. The encapsulation process efficiently entrapped the cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) agonist along with mRNA encoding antigens. The targeted nanovaccines (TNVs) exhibited a narrow particle size distribution, ensuring consistent and efficient delivery. These TNVs significantly enhanced gene expression of mRNA, facilitating antigen presentation and immune activation. When compared to non-targeted nanovaccines, TNVs outperformed in terms of antigen presentation and immune activation. Furthermore, the combination of anti-PD-L1 antibodies with TNVs elicited a synergistic anti-tumor effect. This was attributed to the anti-PD-L1 antibodies' ability to overcome the immune suppression of tumor cells. Our findings suggest that the combination treatment elicited the most robust anti-tumor immune activation and immune memory effect. These results indicate that integrating tumor mRNA vaccines with immune checkpoint inhibitors or other immunostimulatory agents may be crucial for enhancing the immune response.

Super-resolution imaging reveals the role of DDR1 cluster in NSCLC proliferation.

Discoidin domain receptor 1 (DDR1), a transmembrane protein, is crucial in tumor development. Prior studies have demonstrated a significant correlation between protein cluster distribution on the cell membrane and tumor evolution. However, the precise spatial distribution characteristics of DDR1 on cell membranes and their impact on tumor development remain unclear. In this study, we conducted gene expression analysis to investigate DDR1 expression in non-small cell lung cancer (NSCLC) and its association with patient prognosis. We also employed direct stochastic optical reconstruction microscopy (dSTORM) imaging to examine DDR1's spatial distribution in NSCLC cells and tissues. Our findings indicate that DDR1 forms larger, tighter, and more abundant clusters in cancer cells and tissues compared to their normal counterparts. Notably, we observed that the enhanced aggregation of DDR1 clusters increased the likelihood of interaction with SRC, thereby activating the SRC-STAT3 signaling pathway in NSCLC cells and promoting cell proliferation. This study provides novel insights into the role of DDR1 aggregation in tumor proliferation, confirms DDR1 as a potential tumor marker, and serves as a valuable resource for future drug development.

A rare case report: co-occurrence of two types of lung cancer with hamartoma and pulmonary tuberculosis.

With the widespread use of low-dose chest Computed Tomography (CT), lung nodules are being increasingly detected. Common pulmonary conditions such as lung adenocarcinoma, lung squamous cell carcinoma, and tuberculosis are typically diagnosable through imaging examinations. Nevertheless, when multiple types of lung cancer are combined with other benign tumors, how can an accurate diagnosis be made? In this report, we present a rare case of a patient with the simultaneous occurrence of lung adenocarcinoma, lung squamous cell carcinoma, pulmonary tuberculosis, and pulmonary hamartoma, which has not been previously reported. This patient underwent surgical intervention in the Department of Thoracic Surgery at the Second Hospital of Jilin University and has now fully recovered and been discharged. The patient's preoperative positron emission tomography-CT(PET-CT)results did not align with the postoperative pathological diagnosis. The imaging findings were atypical, and the pathological diagnosis was exceptionally rare. We share this case report to contribute to the accumulation of clinical experience.

Sectional anatomy aid for improvement of decompression surgery approach to vertical segment of facial nerve.

The aim of this study was to find a surgical approach to a vertical segment of the facial nerve (VFN) with a relatively wide visual field and small lesion by studying the location and structure of VFN with cross-sectional anatomy. High-resolution spiral computed tomographic multiplane reformation was used to reform images that were parallel to the Frankfort horizontal plane. To locate the VFN, we measured the distances as follows: from the VFN to the paries posterior bony external acoustic meatus on 5 typical multiplane reformation images, to the promontorium tympani and the root of the tympanic ring on 2 typical images. The mean distances from the VFN to the paries posterior bony external acoustic meatus are as follows: 4.47 mm on images showing the top of the external acoustic meatus, 4.20 mm on images with the best view of the window niche, 3.35 mm on images that show the widest external acoustic meatus, 4.22 mm on images with the inferior margin of the sulcus tympanicus, and 5.49 mm on images that show the bottom of the external acoustic meatus. The VFN is approximately 4.20 mm lateral to the promontorium tympani on images with the best view of the window niche and 4.12 mm lateral to the root of the tympanic ring on images with the inferior margin of the sulcus tympanicus. The other results indicate that the area and depth of the surgical wound from the improved approach would be much smaller than that from the typical approach. The surgical approach to the horizontal segment of the facial nerve through the external acoustic meatus and the tympanic cavity could be improved by grinding off the external acoustic meatus to show the VFN. The VFN can be found by taking the promontorium tympani and tympanic ring as references. This improvement is of high potential to expand the visual field to the facial nerve, remarkably without significant injury to the patients compared with the typical approach through the mastoid process.

Long non-coding MELTF Antisense RNA 1 promotes and prognosis the progression of non-small cell lung cancer by targeting miR-1299.

This paper explored the influence of long non-coding MELTF Antisense RNA 1 (lncRNA MELTF-AS1) on the prognosis of non-small cell lung cancer (NSCLC), and further deepened the understanding of NSCLC. A total of 130 patients with NSCLC participated in current study to detect and compare lncRNA MELTF-AS1 expression in cancer and normal tissues. Kaplan-Meier analysis and log-rank test were chosen to analyze the effect of MELTF-AS1 expression on the survival of patients within 5 years. The correlation between the expression of MELTF-AS1 and the clinical characteristics of NSCLC patients was analyzed, and the prognostic factors of NSCLC were analyzed by multivariate Cox regression. Subsequently, MELTF-AS1 expression in NSCLC cells were detected. The Cell Counting Kit-8 (CCK-8) and Transwell methods were selected to study the proliferation, migration capability and invasion level of NSCLC cells that silencing MELTF-AS1. Through the luciferase activity assay to explore the relationship between MELTF-AS1 and miR-1299, to further understand the effect of silencing MELTF-AS1 on NSCLC. MELTF-AS1 was increased in NSCLC tissues and cells. Silencing MELTF-AS1 suppressed the proliferation ability, migration capability and invasion level of NSCLC cells, which means that low expression of MELTF-AS1 may be more conducive to patient survival. In addition, through luciferase activity analysis and bioinformatics analysis, MELTF-AS1 has a negative effect on miR-1299, and silencing MELTF-AS1 enhanced miR-1299 expression in NSCLC cells. MELTF-AS1 is highly likely to be a promising prognostic biomarker, and associated with the progression of NSCLC.

Combination of GNRs-PEI/cGAMP-laden macrophages-based photothermal induced in situ tumor vaccines and immune checkpoint blockade for synergistic anti-tumor immunotherapy.

Immunotherapy is an effective strategy to control and eliminate primary and metastatic tumor by restarting and restoring the specific anti-tumor immune response. However, tumor immunotherapy often showed limited efficacy due to the poor T cell responses in vivo and the tumor suppressive microenvironments. Herein, we constructed polyethyleimine modified gold nanorods (GNRs-PEI) by conjugating PEI to GNRs via SAu bonds. GNRs-PEI/cGAMP nanoparticles were formed via electrostatic interaction and then loaded by macrophages. The GNRs-PEI/cGAMP-laden macrophages (GPc-RAWs) were intravenously injected into the tumor bearing mice and the in situ tumor vaccines were obtained after NIR irradiation. Besides, anti-PD-L1 antibody, an immune checkpoint inhibitor, was introduced to reverse immunosuppressive microenvironment and assisted to achieve the synergistic anti-tumor immunotherapy. GNRs-PEI/cGAMP-laden macrophages with NIR irradiation could effectively inhibit the primary tumors, while little effect for the contralateral tumors. When combined with anti-PD-L1 antibody, the combined strategy not only inhibited the growth of primary tumor, but also significantly delayed the proliferation of the contralateral tumors. More importantly, this strategy reversed immunosuppressive microenvironment without obvious side effects. Therefore, this study provided a great immunotherapy platform for the efficient treatment of primary and metastatic tumors.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis.

Objective: The progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis. Results: In total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44-0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25-0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09-0.22) and 0.86 (95% CI: 0.83-0.89), respectively. Conclusion: Neoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.

LncRNA CCDC144NL-AS1 Serves as a Prognosis Biomarker for Non-small Cell Lung Cancer and Promotes Cellular Function by Targeting miR-490-3p.

This study revealed the prognostic significance of long non-coding RNA (lncRNA) CCDC144NL-AS1 in NSCLC patients and discussed the effect and mechanism of proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells. 128 pairs of NSCLC tissues and paracancerous tissues were collected, and qRT-PCR was used to detect the differential expression of lncRNA CCDC144NL-AS1 in all tissues and cells lines. Kaplan-Meier analysis and Cox proportional hazards model analysis were used to estimate the prognostic value of lncRNA CCDC144NL-AS1. CCK-8 and Transwell assays confirmed the effect of lncRNA CCDC144NL-AS1 on the proliferation, migration, and invasion of NSCLC. Bioinformatics was used to predict the microRNAs that lncRNA CCDC144NL-AS1 might bind to miR-490-3p. The regulation of lncRNA CCDC144NL-AS1 on miR-490-3p was verified by luciferase activity assay with wide type or mutation. The expression of lncRNA CCDC144NL-AS1 was enhanced in both NSCLC tissues and cell lines. Patients with overexpression of lncRNA CCDC144NL-AS1 have a poor prognosis, and lncRNA CCDC144NL-AS1 is an independent prognostic factor for NSCLC. Increased the relative expression level of lncRNA CCDC144NL-AS1 can promote the proliferation, migration, and invasion of NSCLC cells. LncRNA CCDC144NL-AS1 might target miR-490-3p. LncRNA CCDC144NL-AS1 can be used as an oncogene of NSCLC to predict patient prognosis and promote tumor proliferation, migration, and invasion by targeting miR-490-3p.

HDAC2 enhances esophageal squamous cell carcinoma development through down-regulating microRNA-503-5p and promoting CXCL10.

OBJECTIVE: Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC. METHODS: ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p. RESULTS: HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells. CONCLUSION: This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.