Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.

There is an unmet clinical need to develop novel strategies to overcome resistance to tyrosine kinase inhibitors (TKI) in patients with oncogene-driven lung adenocarcinoma (LUAD). The objective of this study was to determine whether simvastatin could overcome TKI resistance using the in vitro and in vivo LUAD models. Human LUAD cell lines, tumor cells, and patient-derived xenograft (PDX) models from TKI-resistant LUAD were treated with simvastatin, either alone or in combination with a matched TKI. Tumor growth inhibition was measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and expression of molecular targets was assessed by immunoblots. Tumors were assessed by histopathology, IHC stain, immunoblots, and RNA sequencing. We found that simvastatin had a potent antitumor effect in tested LUAD cell lines and PDX tumors, regardless of tumor genotypes. Simvastatin and TKI combination did not have antagonistic cytotoxicity in these LUAD models. In an osimertinib-resistant LUAD PDX model, simvastatin and osimertinib combination resulted in a greater reduction in tumor volume than simvastatin alone (P < 0.001). Immunoblots and IHC stain also confirmed that simvastatin inhibited TKI targets. In addition to inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, RNA sequencing and Western blots identified the proliferation, migration, and invasion-related genes (such as PI3K/Akt/mTOR, YAP/TAZ, focal adhesion, extracellular matrix receptor), proteasome-related genes, and integrin (α3ß1, αvß3) signaling pathways as the significantly downregulated targets in these PDX tumors treated with simvastatin and a TKI. The addition of simvastatin is a safe approach to overcome acquired resistance to TKIs in several oncogene-driven LUAD models, which deserve further investigation.

Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.

[Combined use of prefabricated rib-locking titanium plate with ultrasound-guided thoracic paravertebral nerve blockade in the treatment of multiple rib fractures among the elderly].

OBJECTIVE: This paper is aimed at investigating the efficacy of combining internal fixation using prefabricated rib-locking titanium plate with ultrasound-guided thoracic paravertebral nerve blockade in treating multiple rib fractures among the elderly. METHODS: Retrospective analysis of 221 elderly patients with multiple rib fractures treated from February 2016 to November 2020. According to whether surgery was performed, they were divided into the plate-blockage combination group (surgical group, 102 cases) and conservative treatment group (non-surgical group, 119 cases). The surgical group consisted of 58 males and 44 females aged from 60 to 85 years old, with an average of (67.2±3.6 ) years old, who suffered from 3 to 12 rib fractures with an average of (5.3±2.1) fractures. The non-surgical group consisted of 66 males and 53 females aged from 60 to 84 years old with an average of (66.8±3.2) years old, who suffered from 2 to 11 rib fractures with an average of(6.1±2.3) fractures. The clinical data, efficacies observed, and complications associated with both groups were compared and analyzed. RESULTS: There was no significant difference in preoperative clinical data between two groups (P>0.05), and all patients were discharged smoothly. Pulmonary infection (P=0.028), atelectasis (P=0.032), respiratory failure (P=0.026), time to get out of bed (P=0.040), time to fracture healing (P=0.035), length of hospital stay in the operation group (P=0.043), visual analogue scale (VAS) at 3 days (P=0.028), 5 days(P=0.032), and 7 days(P=0.019), maximal voluntary ventilation (MVV) at 3 months after surgery (P=0.042), forced expiratory volume in one second (FEV1)(P=0.035), and maximal voluntary ventilation at 6 months, the maximal voluntary ventilation(MVV)(P=0.021) and forced FEV1(P=0.026) were all significantly better than those in non-surgical treatment group. CONCLUSION: For elderly patients with severe multiple rib fractures, the proposed plate-blockade combination can timely and effectively relieve pain, restore thoracic stability, shorten hospital stay, and reduce the incidence of complications such as pulmonary infections and acute respiratory distress syndrome(ARDS) compared with non-surgical treatments. Prefabricated rib-locking titanium plates have proved to demonstrate high clinical efficacy in treating multiple rib fractures among the elderly.

LncRNA OIP5-AS1 Knockdown Facilitated the Ferroptosis and Immune Evasion by Modulating the GPX4 in Oesophageal Carcinoma.

Objective: Oesophageal cancer (EC) is an extremely invasive malignancy, which has bad prognosis that requires safe and effective treatment modalities. Immunotherapy has provided new ideas for the treatment of EC in recent years. This project was conducted to probe into the role and mechanism of lncRNA OIP5-AS1 in ferroptosis and immunotherapy of EC. Methods: Cell viability and multiplication were assessed through CCK-8, colony formation assays. Levels of Fe2+, MDA, and lipid ROS were applied to determine ferroptosis. GPX4 and OIP5-AS1 levels were examined through real-time PCR assay. The relationship between OIP5-AS1 and GPX4 was estimated through RNA immunoprecipitation assay. Flow cytometry was applied to examine the effect of OIP5-AS1 on CD8+ T cells. Results: OIP5-AS1 inhibition significantly inhibited EC cell viability and proliferation, induced ferroptosis, and downregulated GPX4 levels, while GPX4 reversed these effects. OIP5-AS1/GPX4 induced CD8+ T cell interaction and induced apoptosis through PD-1/PD-L1 immune checkpoints of CD8+ T cells. Conclusion: OIP5-AS1/GPX4 promotes EC development and relieved ferroptosis; furthermore, OIP5-AS1/GPX4 facilitated immune evasion via modulation of PD-1/PD-L1, suggesting aiming at OIP5-AS1 is a possible route which might enhance the effectiveness of immunotherapy.

Maximum Spreading of Impacting Ferrofluid Droplets under the Effect of Nonuniform Magnetic Field.

This article investigates the maximum spreading of ferrofluid droplets impacting on a hydrophobic surface under nonuniform magnetic fields. A generalized model for scaling the maximum spreading is developed. It is observed that, if the magnetic field strength is zero, a ferrofluid droplet not only demonstrates similar spreading dynamics as the water droplet but also obeys the same scaling law for the maximum spreading factor. Therefore, this article emphasizes the effects of magnetic field strength. In this regard, a dimensionless parameter (Nm) is introduced as the ratio between inertial force and Kelvin force, with an assumption that the kinetic energy mainly transforms to thermal energy. This parameter allows us to rescale all experimental data on a single curve with the Padé approximant, which is applicable to a wide range of impact velocities and magnetic field strengths.

UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling.

This study was designed to explore the function of UBE4B in the development of lung adenocarcinoma (LUAD) and the role of PP2A/AKT in this process. Bioinformatics analysis, qRT-PCR, western blot, and immunohistochemistry were used to assess the gene expression in clinical samples, human LUAD database, human LUAD tissue microarrays, LUAD cells, and tumor xenograft model, respectively. The UBE4B overexpression and shRNA vector was constructed and transfected into LUAD cells, and the cell viability, migration, lactate production, and glycolysis were detected. The interaction between UBE4B and PP2A was assessed by CoIP and ubiquitination assay. The enhanced UBE4B expression is confirmed in LUAD datasets, clinical samples, human LUAD tissue microarrays and LUAD cells. UBE4B is positively associated with the proliferation, migration, lactate production, and glycolysis in LUAD cells, and UBE4B elevated proliferation, migration, lactate production, and glycolysis are abolished by PP2A overexpression. Mechanistically, UBE4B ubiquitinates PP2A and induces the activation of AKT. In conclusion, UBE4B act as an oncogene in the development of LUAD through PP2A/AKT signaling. UBE4B could be a new target for diagnosis and treatment of lung adenocarcinoma.

SKA3, negatively regulated by miR-128-3p, promotes the progression of non-small-cell lung cancer.

Aim: To investigate the effects of SKA3 on cell proliferation and metastasis in non-small-cell lung cancer (NSCLC) and its underlying mechanism. Methods: Immunohistochemistry was employed to analyze the expression of SKA3 in NSCLC. CCK-8 assay, EdU assay, Transwell assay and flow cytometry analysis were employed to assess cell proliferation, metastatic potential and apoptosis in vitro, respectively. A lung metastasis model was used to evaluate metastasis of NSCLC cells in vivo. A luciferase reporter gene assay was conducted to verify the targeting relationship. Results: SKA3 exhibited high expression in NSCLC tissues and cells. Overexpression of SKA3 remarkably accelerated cell proliferation and metastasis and suppressed apoptosis of NSCLC cells and promoted lung metastasis in a mouse model. miR-128-3p repressed SKA3 expression by targeting it. Conclusion:miR-128-3p inhibited the progression of NSCLC through targeting SKA3.

It is reported that the protein SKA3 can promote the growth and spread of cancer cells in multiple tumors. However, the biological role and action of SKA3 in the progression of non-small-cell lung cancer remain unknown. This study showed that a high level of SKA3 was linked with poor outcomes in non-small-cell lung cancer patients. SKA3 overexpression facilitated cell growth and spread, but inhibited cell death. miR-128-3p directly targeted SKA3 and reversed its effects. Our work suggests that SKA3 and miR-128-3p are promising therapy targets and diagnostic markers for non-small-cell lung cancer.

High integrin α3 expression is associated with poor prognosis in patients with non-small cell lung cancer.

BACKGROUND: We previously showed that α3ß1 integrin is a novel cancer biomarker and drug target in non-small cell lung cancer (NSCLC). This study characterized the integrin α3 (ITGA3) expression on patient specimens. METHODS: Tissue microarrays (TMAs) were prepared from archival tissue blocks containing 161 patients, which included 91 adenocarcinoma (LUAD), 46 squamous carcinomas (LUSC), and 24 other histology types. TMA sections were stained and scored for ITGA3 expression by immunohistochemistry (IHC). Kaplan-Meier curves and log-rank tests were used to compare overall survival (OS) between IHC score groups. Propensity-score-weighted Kaplan-Meier curves and weighted Cox models were used to adjust for covariate imbalance between IHC score groups. Logistic regression was used to determine ITGA3 transcriptome expression in NSCLC in The Cancer Genome Atlas (TCGA). RESULTS: ITGA3 IHC expression (1+ to 3+) was detected in 107/161 (66.5%) of the NSCLC samples, and was associated with poor prognosis at the edge of significance (HR =1.30, 95% CI: 0.99-1.71, P=0.056), but significant (P<0.05) in subgroups of female patients, smokers and tumors with grade I and II differentiation using propensity-score-weighted survival analysis after adjusting for confounders. Multivariate survival analysis based on multiple imputation for missing variables showed ITGA3 expression, old age and metastasis were associated with poor prognosis (P<0.05). ITGA3 IHC expression was associated with poor prognosis in LUSC (HR =2.27, P<0.05) but not in LUAD (HR =1.49, P=0.16). Median ITGA3 expression was significantly higher in LUAD than LUSC (P<0.0001) in the TCGA transcriptome datasets. Using a higher cutoff than LUSC (70.6 vs. 19.5 FPKM), high ITGA3 RNA expression was also associated with poor prognosis in LUAD (P=0.023). ITGA3 interacted with key genes regulating epithelial to mesenchymal transition, angiogenesis, invasion and metastasis in both LUAD and LUSC. CONCLUSIONS: High ITGA3 IHC expression was associated with poor prognosis in NSCLC patients. Further study is warranted for targeting α3ß1 integrin in NSCLC.

Airway reconstruction using decellularized aortic xenografts in a dog model.

Tracheal reconstruction after extensive resection remains a challenge in thoracic surgery. Aortic allograft has been proposed to be a potential tracheal substitute. However, clinically, its application is limited for the shortage of autologous aortic segment. Whether xenogeneic aortic biosheets can be used as tracheal substitutes remains unknown. In the present study, we investigated the possibility in dog model. The results show that all dogs were survived without airway symptoms at 6 months after tracheal reconstruction with gently decellularized bovine carotid arteries. In the interior of engrafted areas, grafted patch integrated tightly with the residual native tracheal tissues and tracheal defects in the lumen were repaired smoothly without obvious inflammation, granulation, anastomotic leakage, or stenosis. In addition, histological and scanning electron microscopy examination showed that grafted patches were covered with ciliated columnar epithelium similar to epithelium in native trachea, which indicated successfully re-epithelialization of decellularized bovine carotid arteries in dogs. These findings provide preclinical investigation of xenogeneic aortic biosheets in serving as tracheal substitute in a dog model, which proposes that decellularized biosheets of bovine carotid may be a potential material for bioartificial tracheal graft.

Circ_ZNF124 promotes non-small cell lung cancer progression by abolishing miR-337-3p mediated downregulation of JAK2/STAT3 signaling pathway.

BACKGROUND: Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, however, the role of circ_ZNF124 in non-small cell lung cancer (NSCLC) is still unknown. The purpose of this study was to investigate the role and molecular mechanism of circ_ZNF124 in NSCLC development. METHODS: The expression of circ_ZNF124, miR-337-3p and JAK2 (Janus Kinase 2) in lung cancer cell lines and normal epithelial cells were detected by qRT-PCR (quantitative real-time PCR). siRNA was used to knockdown circ_ZNF124 expression in cells. The effects of circ_ZNF124 in NSCLC cells were determined by cell growth, cell migration, cell cycle analysis and colony formation. Bioinformatics analysis, RNA immunoprecipitation, luciferase assay and western blots were used to study the molecular mechanism of circ_ZNF124 in NSCLC. RESULTS: The results showed that circ_ZNF124 expression was highly upregulated in NSCLC cells than in normal epithelial cells. Knockdown of circ_ZNF124 by using siRNA significantly decreased cell growth, promoted cell cycle arrested in sub-G1 phase, impaired cell migration and colony formation. Bioinformatic analysis discovered that miR-337-3p was a direct target of circ_ZNF124. In contrast to circ_ZNF124, miR-337-3p expression was significantly downregulated in NSCLC cells. Biotin labeled circ_ZNF124 immunoprecipitation and luciferase assay showed that miR-337-3p could directly bind to and affect circ_ZNF124 activity. The regulation of circ_ZNF124 on miR-337-3p was also investigated. Further analysis showed that despite STAT3 (signal transducer and activator of transcription 3), JAK2 was also a target of miR-337-3p, overexpression of miR-337-3p greatly downregulated JAK2, STAT3 and JAK2/STAT3 downstream regulated oncogenes HIF1a (Hypoxia-inducible factor 1-alpha), BCL2 (B cell lymphoma 2) and c-FOS expression, however, the roles of miR-337-3p in JAK2/STAT3 signaling pathway were greatly inhibited in the presence of circ_ZNF124. CONCLUSION: In NSCLC, highly expressed circ_ZNF124 promoted the activation of JAK2/STAT3 signaling pathway by acting as a sponge of miR-337-3p, thus promoting the occurrence and development of NSCLC. Circ_ZNF124 could be a potential biomarker or target for the treatment of NSCLC patients in the future.

Correction to: High-affinity peptide ligand LXY30 for targeting α3ß1 integrin in non-small cell lung cancer.

The original article [1] contains an error in Fig. 2 whereby Fig. 2D has mistakenly been omitted. Fig. 2 can be viewed in its entirety - including Fig. 2D - in this Correction article.

High-affinity peptide ligand LXY30 for targeting α3ß1 integrin in non-small cell lung cancer.

BACKGROUND: α3ß1 integrin is a promising cancer biomarker and drug target. We previously identified a 9-amino-acid cyclic peptide LXY30 for detecting α3ß1 integrin on the surface of live tumor cells. This study was undertaken to characterize LXY30 in the detection, cellular function, imaging, and targeted delivery of in vitro and in vivo non-small cell lung cancer (NSCLC) models. METHODS: The whole-cell binding assay was performed by incubating NSCLC cells, extracellular vesicles (EVs), and peripheral blood mononuclear cells (PBMCs) with TentaGel resin beads coated with LXY30. In this study, we defined the nanosize EVs as exosomes, which were characterized by flow cytometry, transmission electron microscopy, dynamic light scattering, and Western blots. The function of LXY30 was determined by modulating the epidermal growth factor receptor (EGFR) signaling pathway by growth inhibition and Western blots. For in vivo biodistribution, mice bearing subcutaneous and intracranial NSCLC xenograft tumors were administrated intraveneously with LXY30-biotin/streptavidin-Cy5.5 complex and then analyzed for in vivo and ex vivo optical imaging and histopathology. RESULTS: We showed that LXY30 specifically and sensitively detected α3ß1 integrin-expressing NSCLC cells and tumor-derived exosomes. Tumor DNA isolated from LXY30-enriched plasma exosomes might be used to detect driver oncogenic mutations in patients with metastatic NSCLC. LXY30 only enriches tumor cells but not neutrophils, macrophages, or monocytes in the malignant pleural effusion of NSCLC patients for detecting genomic alterations by next-generation sequencing. LXY30 detected increased α3ß1 integrin expression on the EGFR-mutant NSCLC cells with acquired resistance to erlotinib compared to parental erlotinib-sensitive EGFR-mutant NSCLC cells. We further showed that LXY30 modulated the EGFR signaling pathway independently from another peptide ligand LXW64 targeting αvß3 integrin in erlotinib-resistant, EGFR-mutant H1975 cells. Analysis of The Cancer Genome Atlas (TCGA) revealed high α3 integrin expression was associated with poor prognosis in lung squamous cell carcinoma. LXY30-biotin/streptavidin-Cy5.5 complex had higher uptakes in the subcutaneous and intracranial xenografts of various α3ß1 integrin-expressing lung adenocarcinoma and patient-derived lung squamous cell carcinoma xenografts while sparing the surrounding normal tissues. CONCLUSION: LXY30 is a promising peptide for the cancer diagnosis and in vivo targeted delivery of imaging agents and cancer drugs in NSCLC, independent of histology and tumor genotype.

FAM46B suppresses proliferation, migration and invasion of non-small cell lung cancer via ß-catenin/MMP7 signaling.

BACKGROUND: This study investigated the functions of FAM46B in non-small cell lung cancer (NSCLC) cells and determined the role of ß-catenin/matrix metalloproteinase 7 (MMP7) signaling in mediating these functions. METHODS: Human paracancerous and cancer tissues were collected from lung cancer patients. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay while migration and invasion were examined by transwell chamber assays. Relative mRNA expression and protein levels were determined by quantitative reverse transcription (q-RT) polymerase chain reaction (PCR) and western blot, respectively. RESULTS: FAM46B displayed reduced expression in lung cancer tissues compared with paired paracancerous tissues. In contrast, ß-catenin protein levels were elevated in lung cancer tissues compared with paired paracancerous tissues. FAM46B over-expression reduced proliferation, migration and invasion of A549 and H292 cells, as well as decreased the protein levels of ß-catenin, MMP7 and vascular endothelial growth factor (VEGF). On the other hand, FAM46B knockdown by shRNA in H1975 cells enhanced proliferation, migration and invasion, as well as increased the protein levels of ß-catenin and MMP7. These enhanced effects were ameliorated by treatment with the Wnt/ß-catenin inhibitor XAV939, suggesting a role for Wnt signaling in mediating the functions of FAM46B in NSCLC. CONCLUSIONS: FAM46B functions as a tumor suppressor by inhibiting ß-catenin/MMP7 signaling.

Identification of a prognostic 5-Gene expression signature for gastric cancer.

PURPOSE: Gastric cancer (GC) is a major tumor throughout the world with remaining high morbidity and mortality. The aim is to generate a gene model to assess the prognoses risk of patients with GC. METHODS: Gene expression profiling of gastric cancer patients, GSE62254 (300 samples) and GSE26253 (432 samples), was downloaded from Gene Expression Omnibus (GEO) database. Univariate survival analysis and LASSO (Least Absolute Shrinkage and Selectionator operator) (1000 iterations) of differentially expressed genes in GSE62254 was assessed using survival and glmnet in R package, respectively. Kaplan-Meier analysis on the clustering algorithm from each regression model was performed to calculate the influence to the prognosis. Random samples in GSE26253 were analyzed in multivariate and univariate survival analysis for one thousand times to calculate statistical stability of each regression model. RESULTS: A total of 854 Genes were identified differentially expressed in GSE62254, among which 367 Genes were found influencing the prognoses. Six gene clusters were selected with good stability. Hereinto, five or more genes in 11-Gene model, TRPC1, SGCE, TNFRSF11A, LRRN1, HLF, CYS1, PPP1R14A, NOV, NBEA, CES1 and RGN, was available to evaluate the prognostic risk of GC patients in GSE26253 (P = 0.00445). The validity and reliability was validated. CONCLUSION: In conclusion, we successfully generated a stable 5-Gene model, which could be utilized to predict prognosis of GC patients and would contribute to postoperational treatment and follow-up strategies.

Multiple mutations of lung squamous cell carcinoma shared common mechanisms.

Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancers which is the cause of 80% of all lung cancer deaths. The genes that highly mutated in patients with LUSC and their roles played in the tumorigenesis remains unknown. Data of patients with Lung squamous cell carcinoma (LUSC) were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified between control and cancer samples. Patients and controls can be separated by mRNA expression level showing that the between-group variance and totally 1265 genes were differentially expressed between controls and patients. Top genes whose mutations highly occurred in patients with LUSC were identified, most of these genes were shown to be related with tumorigenesis in previous studies. All of the genes mostly mutated were independently correlated with expression levels of all genes. These mutations did not show the trend of co-occurrence. However, the influenced gene of these mutations had overlaps. After studying the intersection of these genes, a group of shared genes were identified. The shared pathways enriched which played critical role in LUSC were identified based on these shared genes. Different mutations had contribution to the progression of LUSC. Though these genes involved different specific mechanisms, most of them may share a common mechanism which is critical for LUSC. The results may suggest a neglected mechanism and also indicate a potential target for therapies.

MiR-96 downregulates RECK to promote growth and motility of non-small cell lung cancer cells.

MicroRNAs play critical roles in the development and progression of non-small cell lung cancer (NSCLC). miR-96 acts as an oncogene in some malignancies, while its role in NSCLC is unclear. Here, we validated that miR-96 was significantly increased in both human NSCLC tissues and cell lines. Inhibition of miR-96 expression remarkably reduced cell proliferation, colony formation, migration, and invasion of NSCLC cells. Reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was identified as a target of miR-96 in NSCLC cells. In addition, the expression of RECK was found to be negatively correlated with the expression of miR-96 in NSCLC tissues. Our data suggest that miR-96 might promote the growth and motility of NSCLC cells partially by targeting RECK.

[Comparative study of expressions of P16 protein in patients suffered from non-small-cell-lung-cancer of Xuanwei and Kunming district].

OBJECTIVE: To study the effect and function of P16 protein during the development of lung cancer, in order to explore the differences of expression of P16 protein in non-small cell lung cancer (NSCLC) between Xuanwei and Kunming district. METHODS: 45 patients with NSCLC from Xuanwei and 45 patients from Kunming,18 patients from pneumatocele who underwent radical resection were collected. Immunohistochemical staining were used to analyze the expressions of P16 protein in paraffin-embedded tissues from these 90 residing patients with lung cancer. RESULTS: 45 cases with lung cancer were negative for P16 protein expression, total loss expression rates were 41.7% (45/108). Loss expression rates of Xuanwei,Kunming and pneumatocele were 57.8% (26/45), 37.8% (17/45), 11.1% (2/18), respectively. In comparition the loss expression of P16 protein in clinicopathologic characteristics between the two groups, there were some statistically significant differences in the loss expression rate of P16 (P < 0.05): the loss expression rate of P16 in cases with stage I, adenocarcinoma and stage T2 in Xuanwei were more higher than those in Kunming; the loss expression rates of P16 in Xuanwei and Kungming were more higher than those in pneumatocele respectively. CONCLUSION: Loss expression rates of P16 protein in the early stage and adenocarcinoma in Xuanwei lung cancer group were significant difference compared with in Kunming lung cancer group.