Construction of Prognostic Prediction Model for Lung Squamous Cell Carcinoma Based on Cuproptosis-related LncRNAs / 肿瘤防治研究

Objective To develop a new risk scoring model based on cuproptosis-related lncRNAs (CRLs) to predict the prognosis of lung squamous cell carcinoma (LUSC). Methods Data were obtained mainly from TCGA and GTEx databases. Univariate Cox, Lasso, and multivariate Cox regression analyses were conducted to determine CRLs that affect the prognosis of LUSC and establish a risk scoring model. The ability of risk score characteristics to independently predict LUSC survival was compared with that of clinical characteristics by calculating the area under the ROC curve (AUC). Immune-related functions and immune checkpoint differences were compared between high- and low-risk groups. Results Nine CRLs were selected as independent prognostic lncRNAs for LUSC, and a risk scoring model was developed. Risk score was the influence factor for the prognosis of LUSC. The AUC values predicted by the risk score model for 1-, 3-, and 5-year survival rates of patients with LUSC were 0.710, 0.718, and 0.743, respectively. The high- and low-risk groups were partly statistically different in terms of immune-related functional assays and immune checkpoint assays (P < 0.05). Conclusion The risk scoring model developed based on nine CRLs could predict the prognosis and immune therapy response of patients with LUSC in clinical practice.

A Case of Lung Squamous Cell Carcinoma Retroperitoneal Lymph Node Metastasis Whose Lymphedema Was Improved by Radiation Therapy and Was Temporarily Discharged from the Hospital

The patient was a 73-year-old woman. She had been treated for squamous cell carcinoma of the lung (cT3N3M0, Stage IIIC) at our department. The patient had low back pain due to retroperitoneal lymph node metastasis; in June 2022, this was exacerbated as lung cancer progressed. She had difficulty in body movements due to edema in both lower limbs, in addition to the pain. Consequently, she was urgently admitted on July 8 and received radiotherapy (30 Gy/10 fractions) for retroperitoneal lymph node metastasis. She was being given tapentadol at a dose of 200 mg/day for relief of her pain. However, she was switched to fentanyl patch at a dose of 1200 µg/day during her hospitalization, which resulted in relief of low back pain. The underlying disease causing the edema was investigated. Based on physical and laboratory findings and medical history, lymphedema associated with retroperitoneal lymph node metastases was diagnosed. On day 31 of hospitalization, the patient was allowed to be temporarily discharged from the hospital because the edema had improved and the activity of daily living around the bed had increased. Treatment methods for lymphedema associated with lymph node metastasis have not been established, but the efficacy of radiotherapy has been reported. We have herein reported a case of lymphedema that was improved by radiotherapy after it was differentiated from other diagnoses.

LncRNA FENDRR Affect Proliferation, Migration and Apoptosis of Lung Squamous Cell Carcinoma H226 Cells via ERK/MAPK Signaling Pathway / 肿瘤防治研究

Objective To investigate the effects of lncRNA FENDRR on the proliferation, migration, invasion and apoptosis of LUSC H226 cells and its molecular mechanism. Methods The expression levels of FENDRR in normal lung epithelial cells BEAS, lung adenocarcinoma A549 and H1299 cells and LUSC H226 cells were detected by qRT-PCR. H226 cells were transfected with FENDRR-siRNA as the experimental group, or with FENDRR-siNC as a negative control group. Cell proliferation was detected by CCK-8 assay. Cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. The protein expression levels of MEK, p-MEK, ERK and p-ERK were determined by Western blot. Results FENDRR levels in H226 cells were significantly lower than those in normal lung epithelial cells. Compared with the negative control group, the knockdown of FENDRR could significantly promote the proliferation, migration and invasion of H226 cells, inhibit the cell apoptosis, and increase the protein levels of p-MEK and p-ERK. The addition of ERK inhibitor U0126 rescued the effect of FENDRR knockdown on H226 cells. Conclusions The knockdown of lncRNA FENDRR can promote the proliferation, migration and inhibit the apoptosis of H226 cells through ERK/MAPK pathway.

Influence of SLC16A Family on Clinical Features and Biological Behaviours of Lung Adenocarcinoma and Squamous Cell Carcinoma / 肿瘤防治研究

Objective To explore the relation between SLC16A family and clinical characteristics, biological behavior of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods The expression of 14 members of the SLC16A family in LUAD tissues, LUSC tissues and normal tissues in TCGA database was analyzed by Wilcoxon signed rank sum test. Cox regression was used to evaluate the relation between the family and overall survival, progression-free survival of LUAD and LUSC patients. Logistic regression was used to evaluate the relation between the family and TNM, clinical stage of LUAD and LUSC patients. Principal component analysis was used to establish a Score-SLC16As that comprehensively reflected the family in LUAD and LUSC. ROC, Log rank analysis and univariate and multivariate Cox regression analyses were applied to evaluate the diagnostic effect and survival prediction function of Score-SLC16As on LUAD and LUSC respectively. GSEA was used to evaluate the biological significance of Score-SLC16As and CIBERSORT/Immune checkpoint clusters were used to assess the immune status of Score-SLC16As in LUAD and LUSC. Results In LUAD and LUSC, most members of SLC16A family were differentially expressed and significantly correlated with survival prognosis. Score-SLC16As can clearly diagnose LUAD and LUSC, significantly predict survival prognosis, and can be used as an independent risk factor. Score-SLC16As is a risk factor for LUAD but a protective factor for LUSC. Score-SLC16As is closely related to tumor proliferation pathways and immune escape. Conclusion The SLC16A family is closely related to the clinical features and malignant biological behaviors of LUAD and LUSC.

Atypical MSCT pleomorphic signs in metastatic adenocarcinoma and squamous cell carcinoma of the lung / 国际肿瘤学杂志

Objective:To investigate the correlations between multi-slice spiral CT (MSCT) atypical pleomorphic signs and pathological findings of lung metastases.Methods:From January 2012 to July 2019, the MSCT chest imaging data of 168 metastatic tumor of lung from the General Hospital of Central Theater Command of the Chinese People′s Liberation Army and Shaanxi Provincial Tumor Hospital were collected. According to the pathological type, they were divided into metastatic adenocarcinoma group ( n=88) and metastatic squamous cell carcinoma group ( n=80). The atypical imaging signs of MSCT of the two groups were observed and recorded, and classified after labeling one by one. The difference of atypical MSCT imaging features between the two groups was compared, and the correlations between lesion size and atypical imaging features of MSCT in the metastatic adenocarcinoma group and metastatic squamous cell carcinoma group were analyzed. Results:The spicule sign in metastatic adenocarcinoma and metastatic squamous cell carcinoma were 61 (69.32%) and 28 (35.00%), with a statistically significant difference ( χ2=19.811, P<0.001). The pleural depression sign in the two groups were 48 (54.55%) and 16 (20.00%), and there was a statistically significant difference ( χ2=21.206, P<0.001). The vacuole/cavity sign in the two groups were 10 (11.36%) and 61 (76.25%), and there was a statistically significant difference ( χ2=72.303, P<0.001). The air bronchial sign in the two groups were 43 (48.86%) and 13 (16.25%), with a statistically significant difference ( χ2=20.057, P<0.001). The halo sign/ground glass shadow in the two groups were 58 (65.91%) and 37 (46.25%), with a statistically significant difference ( χ2=6.591, P=0.010). The results of the Spearman rank correlation analysis indicated a positive correlation between the size of metastatic adenocarcinoma and spicule sign, pleural depression sign ( r=0.270, P=0.011; r=0.226, P=0.035). There was no correlation between the nodule size and atypical MSCT imaging features in metastatic squamous cell carcinoma (all P>0.05). Conclusion:The atypical MSCT of metastatic lung adenocarcinoma are mostly spicule sign, pleural depression sign, air bronchial sign and halo sign/ground glass shadow. The characteristic atypical imaging of metastatic squamous cell carcinoma is vacuole/cavity sign. The spicule sign and pleural depression sign are related to the size of metastatic lung adenocarcinoma nodules.

LINC00355 promoted the progression of lung squamous cell carcinoma through regulating the miR-466/LYAR axis

LINC00355 has been reported aberrantly over-expressed and associated with poor prognosis in various types of cancer. However, reports regarding the effect of LINC00355 on lung squamous cell carcinoma (SCC) are rare. This study aimed to explore the function of LINC00355 in the development and progression of lung SCC and reveal the underlying mechanism. The expression and subcellular location of LINC00355 were determined by qRT-PCR and RNA-FISH, respectively. The lung SCC cell growth was analyzed by CCK-8 assay, transwell invasion, wound healing, colony formation, and flow cytometry assays. Reactive oxygen species level was evaluated by DCFH-DA probes. Bioinformatics online websites, luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), and RNA pull-down assays were utilized to investigate the interaction among LINC00355, miR-466, and Ly-1 antibody reactive clone (LYAR). The results showed that LINC00355 was upregulated in lung SCC and was positively associated with poor overall survival in lung SCC patients. LINC00355 was mainly located in the cytoplasm of SCC cells. Additionally, LINC0035 functioned as a competing endogenous RNA (ceRNA) to target miR-466, and LYAR was identified as a direct target of miR-466. LINC00355 expression negatively correlated with miR-466 level, and positively correlated with LYAR level. Mechanistically, knockdown of LINC00355 inhibited cell proliferation, migration and invasion, promoted cell apoptosis in vitro, and suppressed tumor growth in vivo through targeting miR-466, and thus down-regulated LYAR expression. These findings provide a new sight for understanding the molecular mechanism of lung SCC and indicate that LINC00355 may serve as a potential biomarker for the diagnosis and treatment of lung SCC.

Effects of FRZB mRNA in adjusting WNT signal pathway for prognosis of non-small cell lung cancer / 临床检验杂志

Objective@#This study aimed to reveal the potential clinical and biological functions of frizzled related protein (FRZB) mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). @*Methods@#We used the keyword “lung cancer” to search the data through Gene Expression Omnibus (GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA (The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio (HR). @*Results@#We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR（95%CI）=0.54（0.46-0.64）,P＜0.05 in univariate analysis; pooled HR（95%CI）=0.66（0.54-0.79）,P＜0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR（95%CI）=1.11（0.67-1.84）,P＞0.05 in univariate analysis; pooled HR（95%CI）=1.13（0.71-1.78）,P＞0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. @*Conclusion@#High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.

Identification of differentially expressed genes between lung adenocarcinoma and squamous cell carcinoma using transcriber signature analysis / 南方医科大学学报

OBJECTIVE@#To analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC).@*METHODS@#The gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, and , in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues.@*RESULTS@#GEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC.@*CONCLUSIONS@#Through transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.

Pooled analysis of prognostic significance of CX3CL1 mRNA expression level in patients with non-small cell lung cancer / 医学研究生学报

Objective The prognostic expression level and prognostic significance of CX3CL1 in patients with non-small cell lung cancer(NSCLC) need further investigation. The purpose of this paper was to investigate the effects of various CX3CL1 mRNA expression levels on patients with NSCLC.Methods By retrieving lung-cancer related gene expression profile data in NCBI GEO database and TCGA of UCSC Cancer Browser, 8 datasets were included based on inclusion and exclusion criteria. All the datasets were collated and standardized through R statistical software. Univariate and multivariate Cox models were conducted for prognosis analysis of CX3CL1 in each dataset. HR values of all the datasets were pooled by meta algorithm.Results High-expression of CX3CL1 mRNA in tumor tissues of lung adenocarcinoma was a positive prognostic factor for overall survival(pooled HR=0.53; 95% CI=0.43-0.65 in univariate analysis; pooled HR=0.52; 95% CI=0.42-0.64 in multivariate analysis). However, in lung squamous cell carcinoma, there was no significant association between CX3CL1 expression and overall survival (pooled HR=1.09; 95% CI=0.82-1.45 in univariate analysis; pooled HR=1.18; 95% CI=0.88-1.58 in multivariate analysis).Conclusion The mRNA level of CX3CL1 in lung adenocarcinoma was positively correlated with better prognosis, but there was no correlation between CX3CL1 mRNA level and prognosis in patients with lung squamous cell carcinoma. CX3CL1 may be used as a potential prognostic marker for patients with lung adenocarcinoma.

Treatment of lung squamous cell carcinoma with apatinib in patient who couldn't tolerate chemotherapy: A case report and literature review / 吉林大学学报(医学版)

Objective: To analyze the efficacy of apatinib in the treatment of a patient with lung squamous cell carcinoma who couldn' t tolerare the chemotherapy and review the literature, and to clarify the effectiveness of apatinib in order to provide the treatment reference. Methods: The patient was clearly diagnosed as stage Flung squamous cell carcinoma. After four cycles of chemotherapy, there was no significant change of the tumor volume, while the patient couldn' t tolerate the side effects caused by chemotherapy. Then the disease progressed rapidly. The primary lesion and multiple metastases responded significantly to the radiotherapy. However, the lesions were too extensive to radiotherapy, therefore, apatinib (500 mg • d-1, 40 d) was used to inhibit the progression of disease. Results: After the application of apatinib, the volumes of both lesions in chest wall and lung shrank greatly compared wtih before administration. The patient developed myelosuppression (grade E thrombocytopenia) and stopped taking apatinib. Then the volume of lesion in chest wall was increased. The dosage of apatinib reduced to 250 mg . d-1 , and the progression free survival (PFS) of the patient reached to 5 months. Conclusion: For the patients with lung squamous cell carcinoma who couldn ' t tolerate chemotherapy or fail in multiple lines of chemotherapy, apatinib has better efficacy with controllable side effects.

The value of multimodal MRI in differential diagnosis of lung squamous cell carcinoma and adenocarcinoma / 实用放射学杂志

Objective To evaluate the value of multimodal MRI in differential diagnosis of lung squamous cell carcinoma and adenocarcinoma.Methods Routine sequence,diffusion weighted imaging(DWI)and dynamic enhancement images about 1 6 squamous cell carcinoma and 21 adenocarcinoma patients were analyzed retrospectively.Taken a record about the size,edge,internal signal, enhancement types and apparent diffusion coefficient(ADC)values when b=600 s/mm2,and the difference in the degree of pathological differentiation was studied.Results The average diameter of squamous cell carcinoma was (4.17±2.0)cm,while adenocarcinoma was (3.81±1.8)cm,lobulated and spiculation were the most common signs in both of them.Squamous cell carcinoma showed low T1signal in 12 cases(75%),low T2signal in 7 cases(43.7%),adenocarcinoma showed high T1signal in 10 cases(47.6%),high T2 signal in 14 cases(66.7%).Squamous cell carcinoma had lower ADC value than adenocarcinoma(1.27×10-3mm2/s vs 1.38×10-3mm2/s), and well differentiated tumors had higher ADC values than poor ones,it was statistically significant.The most common time-signal intensity curves were type A in squamous cell carcinoma(62.5%)and type B in adenocarcinoma(50%).Conclusion MRI findings of squamous cell carcinoma and adenocarcinoma are associated with the biological characteristics,squamous cell carcinoma has shorter T2signal and adenocarcinoma has shorter T1signal.Squamous cell carcinoma has lower ADC value than adenocarcinoma and is dominated by outflow curve (type A),these features are helpful in subtype and differential diagnosis.

Microwave Hyperthermia Combined with Gemcitabine Inhibits Proliferation and Induces Apoptosis of Human Lung Squamous Carcinoma Cells / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the highest morbidity and mortality in the world and it is very important to find an effective anti-tumor method. Microwave hyperthermia, a new treatment technology, has been getting more and more attention. This study was designed to investigate the effects of microwave hyperthermia combined with gemcitabine on the proliferation and apoptosis of human lung squamous cell carcinoma (NCI-H1703 and NCI-H2170) in vitro.@*METHODS@#The proliferation of cells treated with microwave hyperthermia, the effect of gemcitabine on cell proliferation and the proliferation of cells treated with different methods of microwave hyperthermia and gemcitabine were detected by CCK-8 assay. Colony formation assay was used to measure the colony formation of human lung squamous cell carcinoma cells. Flow cytometry assay was used to detect the total apoptosis rates of the treated cells. Caspase-3, Caspase-8 activity assay was used to detect the activity of Caspase-3, Caspase-8 enzyme in each group of cells. CCK-8 assay was used to detect the effect of control group, AC-DEVD (Caspase-3 inhibitor) group, thermalization combined group, and thermal AC-DEVD combined group on cell proliferation. The levels of p53, Caspase-3, Cleaved-Caspase-3, PARP, Bax and BCL-2 protein expression were detected using Western blot assay.@*RESULTS@#Our results demonstrated that microwave hyperthermia inhibited the proliferation of lung squamous cell carcinoma. The IC₅₀ values of gemcitabine for the two cells were 8.89 μmol/L and 44.18 μmol/L, respectively. The first chemotherapy after microwave hyperthermia has synergistic effect on the two lung squamous cell carcinoma cells and can significantly inhibit the cell clone formation (P0.05). Furthermore, Western blot analysis showed that microwave hyperthermia combined with gemcitabine could up-regulate the p53, Caspase-3, Cleaved-Caspase-3, Cleaved-PARP and Bax protein expression.@*CONCLUSIONS@#Microwave hyperthermia combined with gemcitabine remarkably inhibit the proliferation and induce apoptosis of human lung squamous cell carcinoma in vitro. This effect may be associated with the activation of p53, cleavage of PARP protein, and induced the Caspase-3 dependent apoptosis.

Relationship between BRCA1 protein expression in lung cancer tissues and the efficacy of chemotherapy / 中国生化药物杂志

Objective To investigate the relationship between BRCA1 protein expression in lung cancer tissues and the effect of gemcitabine and Cisplatin based chemotherapy.Methods 80 cases of squamous cell carcinoma confirmed by pathology from May 2013 to May 2015 were selected, and treated with gemcitabine plus cisplatin chemotherapy and Ginseng and Astragalus assisted theropy.BRCA1 protein expression of all patients were detected, and relationship between the effect of chemotherapy and prognosis of patients with BRCA1 protein expression in lung cancer tissues were studied.Results In 80 cases, BRCA1 protein was positive in 40 cases, 40 cases were negative, CR 5 patients, PR 6 patients with BRCA1 positive expression, the remission rate was lower than the BRCA1 negative patients ( P <0.05 ) .80 cases of adverse reactions were seen as leukopenia, gastrointestinal symptoms (nausea and vomiting), abnormal liver function, BRCA1 expression of peripheral neurotoxicity, the incidence of complications in patients with positive expression were significantly higher than BRCA1 negative patients(P<0.05).N stage (P=0.03), BRCA1 gene (P=0.02) were independent risk factors of the prognosis of patients.Conclusion BRCA1 protein positive patients in lung cancer tissue had poor chemotherapy effect, more adverse reactions, and poor prognosis.

Diagnostic value of string beads sign in peripheral small cell lung cancer / 实用放射学杂志

Objective To investigate the formation mechanism of string beads sign in peripheral small cell lung cancer (SCLC) and evaluate the significance of it in differential diagnosis among SCLC,peripheral lung adenocarcinoma and peripheral lung squa-mous cell carcinoma.Methods 78 cases of SCLC,69 cases of peripheral lung adenocarcinoma and 33 cases of peripheral lung squa-mous cell carcinoma,confirmed pathologically were included in this study.The positive rates of string beads sign,mediastinal lymph node metastasis and mediastinal lymph nodes larger than primary lung lesions were calculated and analyzed in these three groups.Results 10 out of SCLC cases (12.8%)have string beads sign,in which all mediastinal lymph nodes were larger than lung lesions.Mediasti-nal lymph node metastases were observed in 63(80.8%)of 78 cases,and 42 (53.8%)cases had larger mediastinal lymph nodes than lung lesions.No string beads sign was observed in patients with peripheral solid lung adenocarcinomas,but 25 of 69 cases (36.2%) have mediastinal lymph node metastasis and 2 cases (2.9%)had larger mediastinal lymph nodes than lung lesions.13 cases(39.4%) of 33 patients with peripheral lung squamous cell carcinomas had mediastinal lymph node metastasis,and 6 cases (16.7%)had larger mediastinal lymph nodes than lung lesions.The statistical results showed the positive rate of string beads sign was not significantly different between peripheral SCLC group and peripheral lung squamous cell carcinoma group,but that of mediastinal lymph node and larger mediastinal lymph nodes than lung lesions were statistically different among these three groups.Conclusion To some extent, string beads sign on CT could reflect the biologic character of SCLC.It played an important role in differential diagnosis of peripheral SCLC,peripheral lung adenocarcinoma and periph-eral lung squamous cell carcinoma,but it should be combined with mediastinal lymph node size.

The single-center safety observation of ipilimumab combined with chemotherapy in the treatment of advanced squamous cell carcinoma / 中国癌症杂志

Background and purpose:Checkpiont targeted immunotherapy in the field of solid tumor therapy has huge potential, triggering a boom in the study of immune targeted drugs. A study has provided a basis for the follow-up study of ipilimumab combined with chemotherapy in the treatment of non-small cell lung cancer(NSCLC) patients. This study counted the adverse event statistics that ipilimumab or placebo combined with paclitaxel and carboplatin as first-line therapy for the treatment of stage Ⅳ or recurrent squamous cell carcinoma to evaluate the safety of ipilimumab combined with chemotherapy in the treatment of advanced squamous cell carcinoma.Methods:This study selected 13 patients with ECOG scores≤1 and stage ⅣA or ⅣB squamous cell carcinoma in the Shanghai Chest Hospital, Shanghai Jiao Tong Uni-versity. Randomized controlled double blind trial was used in this study. The patients of experimental group were treated with ipilimumab combined with paclitaxel and carboplatin, while the patients of control group were treated with the placebo combined with paclitaxel and carboplatin. Adverse events (AEs) were counted in the process of treatment.Results:The most common AEs were the 1/2 grade AEs. Immune-related AEs (irAEs) reported in the ipilimumab group included level Ⅰ of diarrhea and pruritus, level Ⅱ of rash and pruritus and level Ⅲ of hypophysitis.Conclusion:The side effects of ipilimumab were mild, tolerable and manageable.

Expression and significance of CD44v6 in lung squamous cell carcinoma tissues before and after neoadjuvant radiotherapy / 中国综合临床

Objective To investigate the effect and clinical significance of neoadjuvant radiotherapy for the expression of CD44v6 in lung squamous cell carcinoma tissues. Methods Fifty cases lung squamous cell carcinoma patients confirmed by aspiration biopsy from May 2013 to January 2015 were collected in Yangquan Coal Mine Group Genernal Hospital,including 20 cases of patients with stageⅢA were treated with neoadjuvant radiotherapy before surgery,and then performed surgery after neoadjuvant therapy. The expression of CD44v6 was detected by immunohistochemistry. The correlation between CD44v6 and clinicopathological features was analyzed by chi?square test. Results Immunohistochemical staining of CD44v6 was performed in tumor tissue of puncture biopsy, the positive rate expression of CD44v6 was 72%( 36/50 ) , it was associated with lymphatic metastasis(χ2 =3. 964, P=0. 046 ) and advanced TNM stage (Ⅲ+Ⅳstage ) (χ2 =4. 276, P=0. 039 ) . The positive expression of CD44v6 protein in tumor tissue was significantly decreased in 20 patients with neoadjuvant radiotherapy compared with before radiotherapy(7. 23±1. 45 vs. 11. 42±1. 31,t=2. 524,P=0. 025). Conclusion Positive expression of CD44v6 in human lung squamous cell carcinoma is related to the malignant clinicopathological features. Neoadjuvant radiotherapy before operation may improve prognosis via down?regulating CD44v6 expression.

Integrated analyses of copy number variations and gene differential expression in lung squamous-cell carcinoma

BACKGROUND: Although numerous efforts have been made, the pathogenesis underlying lung squamous-cell carcinoma (SCC) remains unclear. This study aimed to identify the CNV-driven genes by an integrated analysis of both the gene differential expression and copy number variation (CNV). RESULTS: A higher burden of the CNVs was found in 10-50 kb length. The 16 CNV-driven genes mainly located in chr 1 and chr 3 were enriched in immune response [e.g. complement factor H (CFH) and Fc fragment of IgG, low affinity Ilia, receptor (FCGR3A)], starch and sucrose metabolism [e.g. amylase alpha 2A (AMY2A)]. Furthermore, 38 TFs were screened for the 9 CNV-driven genes and then the regulatory network was constructed, in which the GATA-binding factor 1, 2, and 3 (GATA 1, GATA2, GATA3) jointly regulated the expression of TP63. CONCLUSIONS: The above CNV-driven genes might be potential contributors to the development of lung SCC.

Effect of BMP9 over-expression on migration and invasion of human lung squamous-cell carcinoma NCI-H520 cells / 中国病理生理杂志

AIM:To investigate the effect of bone morphogenetic proteins 9 (BMP9) on the migration and in-vasion abilities of human lung squamous-cell carcinoma NCI-H520 cells and its mechanism.METHODS:The expression of BMP9 at mRNA and protein levels in the NCI-H520 cells and human bronchial epithelial ( HBE) cells was detected by RT-PCR and Western blot.The NCI-H520 cells were transfected with the recombinant adenovirus AdBMP9 and the expres-sion of BMP9 at mRNA and protein levels was validated by RT-PCR and Western blot.The migration and invasion abilities of the NCI-H520 cells were determined by wound-healing and Transwell assays.The mRNA and protein levels of the migra-tion-related factor matrix metalloproteinase 2 (MMP2) were detected by RT-PCR and Western blot.The level of phospho-rylated Smad1/5 (p-Smad1/5) was detected by Western blot.Meanwhile, NCI-H520 cells were treated with BMP specific antagonist AdNoggin and AdBMP9.The level of p-Smad1/5 and the cell migration ability were measured by Western blot, wound-healing and Transwell assays.RESULTS:The expression of BMP9 at mRNA and protein levels was lower in NCI-H520 cells than that in HBE cells.After AdBMP9 was stably transfected into the NCI-H520 cells, the expression of BMP9 at mRNA and protein levels was significantly up-regulated, cell migration and invasion abilities were significantly de-creased, and the mRNA and protein levels of MMP2 were decreased.Meanwhile, the level of p-Smad1/5 was increased. Noggin reversed BMP9-caused the increase in p-Smad1/5 and the decrease in cell migration ability.CONCLUSION:O-ver-expression of BMP9 inhibits the migration and invasion abilities of lung squamous-cell carcinoma NCI-H520 cells.The activation of BMP-Smad signaling pathway may be involved in this inhibitory process.

Expression of OPN protein in lung squamous cell carcinoma tissue and its clinical signiifcance / 中国癌症杂志

Background and purpose:Osteopontin (OPN) is a secreted glyco-phosphoprotein, which is overex-pressed by numerous human cancers, invovled in tumor occurrence, development and prognosis. OPN up-regulates matrix metal proteases (MMPs) expression in a NF-κB-dependent fashion during extracellular matrix (ECM) invasion causing degradation of cell basement membrane and ECM leading to tumor invasion and metastasis. The aim of this study was to examine the protein level of OPN in a large number of tissue samples from patients with lung squamous cell carcinoma (SCC), and evaluate its potential clinical value.Methods:The OPN protein levels in 265 tumor tissue samples and corresponding 24 normal lung tissue samples were examined by immunohistochemical (IHC) analysis.Results:IHC results showed that the positive rate of OPN was 64.5% in the SCC tissues, which was significantly higher than that in normal alveoli tissues (29.2%,P<0.001). The positive rate of OPN expression in late stage (Ⅲ+Ⅳ) tissues was 78.4%, significantly higher than that in early stage (Ⅰ+Ⅱ) tissue(positive rate 54.5%,P<0.001). The positive rate of OPN expression in T3-4 stage (Ⅲ+Ⅳ) tissue was 76.9%, significantly higher than that in T1-2 stage tissue (positive rate 59.4%,P=0.007). The expression of OPN was signifcantly correlated with the status of lymph node metastasis (LNM). The positive rate in the tumor tissue with LNM was 73.4%, significantly higher than that without (positive rate 51.4%,P<0.001).Conclusion:The level of OPN protein was overexpressed in lung cancer tissues, involved in SCC carcinogenesis and LNM. It is indicated that OPN has an impor-tant reference value in diagnosis, prognosis and therapy of SCC.

Effect of epithelial-to-mesenchymal transition on the invasion and migration abilities of lung squamous cell carcinoma / 中国肿瘤临床

Objective:To investigate the clinical significance of epithelial-to-mesenchymal (EMT) in lung squamous cell carcino-ma (LSCC) and to examine the effect of EMT on the invasive and migration abilities of LSCC. Methods:Immunohistochemical stain-ing was performed to determine the expression of E-cadherin, Vimentin, and TGF-β1 in 79 LSCC patients, and the clinical significance was explored. SK-MES-1 lung squamous carcinoma cells were cultured in conditioned medium containing various concentrations of transforming growth factor-β1 (TGF-β1) for 5 and 10 days. The expression levels of E-cadherin and Vimentin were detected via West-ern blot and reverse transcription-polymerase chain reaction (RT-PCR). With different concentrations and induction times, invasion and wound healing assays were performed to evaluate the invasion and migration abilities. Results:E-cadherin expression was significantly lower, whereas Vimentin expression was significantly higher in LSCC with lymph node metastasis than in that without noda metastasis (P<0.05). In the tissues of 79 LSCC patients, TGF-β1 expression was significantly related to lymph node metastasis (P<0.05). Western blot showed that Vimentin expression was higher, whereas E-cadherin expression was lower in TGF-β1 inducing medium with 10 ng/mL SK-MES-1 cells than in the other media. RT-PCR showed similar results. Scratch test and invasion assay both showed that treat-ment of cells with cytokines markedly enhanced the migration and invasion of the cells. Conclusion:Lymph node metastasis of LSCC correlates with EMT. SK-MES-1 cells undergo EMT via TGF-β1 induction, which enhances invasion and migration.