Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i.v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.
This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography (CEUS); and to investigate the angiogenesis features of tumor at different growth time. Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa. Time window for examining CEUS were respectively in 7-day, 14-day and 28-day. The perfusion parameters including rise time (RT), peak intensity (PI), area under the curve (AUC) of lung tumor were obtained on CEUS images by using off-line software Q lab. Immunohistochemically staining for CD34 was used to observe the microvessel density (MVD).The 7-day group had the highest AUC and PI; AUC and PI of 14-day and 28-day group decreased gradually (P < 0.05). RT was increased as tumor growth. In tumor with necrosis, AUC and PI of non-necrosis part were also larger than necrosis part (P < 0.05). Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis (7.50±3.44 vs.12.44±5.74, P=0.034). Pearson correlation indicated that PI was positively related with MVD (r=0.668, P=0.008). Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography. Time-intensity curve parameters including AUC, PI and RT may reflect tumor angiogenesis.
ObjectiveTo observe the effect of lncRNA-metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on colorectal cancer cells-induced angiogenesis, and explore the potential underlying mechanism. MethodsMALAT1 was overexpressed in colorectal cancer cells SW48 by plasmids transfection, then SW48 cells were cultured at normoxia or hypoxia conditions. The culture media was collected, and the concentration of vascular endothelial growth factor (VEGF) in the media was measured by the enzyme-linked immuno sorbent assay (ELISA), and the human umbilical vein endothelial cells (HUVEC) were incubated with the media collected above. Meanwhile, the expression of hypoxia-inducible factor-1α(HIF-1α) in SW48 cells was detected by western blot. ResultsOverexpression of MALAT1 increased the VEGF level in the culture media, normoxia:the MALAT1 group (514±32) mg/L vs. the control group (110±14) mg/L, P < 0.05; hypoxia:the MALAT1 group (928±18) mg/L vs. the control group (230±21) mg/L, P < 0.05. Meanwhile, the tube formation activity of HUVEC was enhanced, and the expression of HIF-1αwas elevated in the MALAT1 group by western blot. ConclusionOverexpression of MALAT1 could promote colorectal cancer cells-mediated angiogenesis, it may be developed as a new drug target for colorectal cancer treatment.
ObjectiveTo investigate the predictive value of thyroid transcription factor-1 (TTF-1) in the treatment of advanced lung adenocarcinoma with different chemotherapy regimens.MethodsA total of 126 patients with advanced lung cancer were divided into three groups according to the chemotherapy regimen, namely a pemetrexed+nedaplatin group (PEM+NDP group), a pemetrexed+cisplatin/carboplatin group (PEM+DDP/CBP group) and a third-generation (3G) chemotherapy+cisplatin/carboplatin group (3G agent+DDP/CBP group). The predictive value of TTF-1 in the above three treatment regimens was analyzed. The patients were followed up by telephone or outpatient visit until April 2017.ResultsThere were no significant differences in disease control rate or objective response rate between the three different chemotherapy regimens (all P>0.05). The survival rate of PEM+NDP group was significantly higher than that of PEM+DDP/CBP group and 3G agent+DDP/CBP group (9.68%vs. 5.56% and 6.80%, both P<0.05). ECOG score and brain metastasis were independent risk factors for the prognosis of chemotherapy regimens. TTF-1 was an independent risk factor for PEM+NDP therapy.ConclusionTTF-1 is an independent risk factor for PEM+NDP chemotherapy, but not for 3G agent + DDP/CBP or PEM+DDP/CBP regimens.
Objective To investigate the relationship between clinical features and lymph node metastasis in lung adenocarcinoma patients with T1 stage. Methods We retrospectively analyzed the clinical data of 253 T1-stage lung adenocarcinoma patients (92 males and 161 females at an average age of 59.45±9.36 years), who received lobectomy and systemic lymph node dissection in the Second Affiliated Hospital of Harbin Medical University from October 2013 to February 2016. Results Lymph node metastasis was negative in 182 patients (71.9%) and positive in 71 (28.1%). Poor differentiation (OR=6.988, P=0.001), moderate differentiation (OR=3.589, P=0.008), micropapillary type (OR=24.000, P<0.001), solid type (OR=5.080, P=0.048), pleural invasion (OR=2.347, P=0.024), age≤53.5 years (OR=2.594, P=0.020) were independent risk factors for lymph node metastasis. In addition, in the tumor with diameter≥1.55 cm (OR=0.615, P=0.183), although the cut-off value of 1.55 cm had no significant difference, it still suggested that tumor diameter was an important risk factor of lymph node metastasis. Conclusion In lung adenocarcinoma with T1 stage, the large tumor diameter, the low degree of differentiation, the high ratio of consolidation, and the micropapillary or solid pathological subtypes are more prone to have lymph node metastasis.
It was a short time from the initial investigation of tumor islands to the concept of tumor spread through air spaces (STAS) being adopted as a pattern of invasion in lung adenocarcinoma. Generally, STAS was defined as "spread of lung cancer cells into air spaces in the lung parenchyma beyond the edge of the main tumor". More and more studies had demonstrated that STAS could increase recurrence rate and cause worse prognosis in lung adenocarcinoma. However, criteria of this definition were various in previous studies, and there is no unified criterion of STAS up to now. In addition, perioperative manipulations including specimen processing and surgery procedure could squeeze tumor cells into alveolar spaces which could affect the assessment of STAS. Obviously, we need a precise definition to reduce and quantify the impacts of confounding factors. We summarize recent developments and put forward some advice for further studies in this article.
ObjectiveTo assess the specific clinicopathological characteristics as well as prognostic value of prognostic significance of spread through air spaces (STAS) in lung adenocarcinoma.MethodsWe systematically searched the databases of PubMed, EMbase and Web of Science databases from their date of inception to March 2019. The quality of the included literature was assessed by the Newcastle-Ottawa scale (NOS). The NOS of the study higher than 6 points was considered as high quality. Software of Stata 12.0 was used for meta-analysis.ResultsTwenty retrospective cohort studies involved with totally 6 225 patients were included. Quality of included studies was high with NOS score equal or higher than 6 points. STAS was associated with male sex, ever smoking history, abnormal carcino-embryonic antigen (CEA) level, air bronchogram negative, anaplasticlymphoma kinase (ALK) arrangement positive, epidermal growth factor receptor (EGFR) mutation positive, advanced pathological tumor stage and more invasive pathological adenocarcinoma subtypes. The presence of STAS indicated significantly poor recurrence free survival (RFS) (HR=1.960, 95%CI 1.718-2.237, P<0.001) as well as poor overall survival (OS) (HR=1.891, 95%CI 1.389-2.574, P<0.001). Further subgroup analyses showed that exhibiting tumor size including diameter less than 2 cm (HR=2.344, 95%CI 1.703-3.225, P<0.001) and diameter over 2 cm (HR=2.571, 95%CI 1.559-4.238, P<0.001), resection type including lobectomy (HR=1.636, 95%CI 1.258-2.127, P<0.001) and sublobar resection (HR=3.549, 95%CI 2.092-6.021, P<0.001) in stageⅠ adenocarcinoma suggested that STAS had a bad effect on RFS.ConclusionPresence of STAS is associated with more aggressive clinicopathological features and independently associated with worse RFS and OS in lung adenocarcinoma. STAS positive has a negative effect on RFS whatever the tumor size (including the diameter<2 cm or >2 cm) and resection types in stageⅠ adenocarcinoma.
With the development of technology, the detection rate of ground-glass opacity (GGO) is rapidly increasing. GGO comprises of pure GGO and mixed GGO. Many researches have studied the characteristics of GGO, and they found that different malignant probability of GGO was associated with different image characteristics. It is obvious that there is a close relationship between the image characteristics of GGO and its prognosis. However, due to the various image characteristics of GGO, it is essential to assess the prognosis of lung adenocarcinoma patients in a more comprehensive way. In this review, we summarize the correlation between the main GGO image features (solid proportion, size, mean CT value, shape characteristics) and the prognosis of lung adenocarcinoma patients, to provide clinical reference for prognosis prediction and decision-making for patients with lung adenocarcinoma.
ObjectiveTo investigate the relationship between the expression of programmed cell death ligand-1 (PD-L1) and the maximal standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the correlation of clinical factors between SUVmax values and PD-L1.MethodsThe clinical data of 84 patients with invasive lung adenocarcinoma diagnosed pathologically in West China Hospital, Sichuan University from August 2016 to November 2018 were analyzed retrospectively, including 38 males and 46 females, aged 60 (32-85) years. The tumor was acinar-predominant in 37 patients, papillary in 20, lepidic in 19, solid in 5 and micropapillary in 3. Multivariate analysis of the relationship between SUVmax value and other clinicopathological features was performed by linear regression. Logistic regression analysis was used to analyze the relationship between PD-L1 protein expression and other pathological features.ResultsThe SUVmax of the PD-L1 expression group was significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group (P=0.002) and intermediate-grade histologic subtype (P=0.016). The SUVmax cut-off value of PD-L1 expression in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype was 5.34 (AUC: 0.732, P=0.002) and 5.34 (AUC: 0.720, P=0.017), respectively. Multivariate analysis showed that pleura involvement, vascular tumor thrombus and the increase of tumor diameter could cause the increase of the SUVmax value, while the SUVmax value decreased in the moderately differentiated tumor compared with the poorly differentiated tumor. The SUVmax cut-off value between low-grade histologic subtype and intermediate-grade histologic subtype, intermediate-grade histologic subtype and high-grade histologic subtypes was 1.54 (AUC: 0.854, P<0.001) and 5.79 (AUC: 0.889, P<0.001), respectively. Multivariate analysis of PD-L1 expression showed pleura involvement (P=0.021, OR=0.022, 95%CI 0.001 to 0.558) and moderate differentiation (opposite to poor differentiation) (P=0.004, OR=0.053, 95%CI 0.007 to 0.042) decreased the expression of PD-L1.ConclusionThe SUVmax of the PD-L1 expression group is significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype. The level of SUVmax and the expression of PD-L1 in invasive lung adenocarcinoma are related to many clinical factors.
ObjectiveTo analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics.MethodsBased on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA).ResultsBased on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway.ConclusionCDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.