Expression Profiles of VEGF-A, CD31 and GRP78 in Non-Small Cell Lung Cancer.

Abstract BackgroundAngiogenesis is mandatory for tumor growth and progression. The modest response to the anti-angiogenic therapies in non-small cell lung cancer reflects the presence of confounding molecular factors. The aims of this study were to investigate the expression levels of VEGF-A, CD31 and GRP78 and test for significant correlations between them.MethodsParaffin-embedded NSCLC tissue samples (71 adenocarcinoma and 23 squamous cell carcinoma) were retrospectively collected from 94 patients who underwent surgical resection between 2008 and 2015; and did not receive chemotherapy or radiotherapy prior to surgery. The expressions of VEGF-A, CD31 and GRP78 were determined by immunohistochemistry. ResultsHigh expression levels of VEGF-A, CD31 and GRP78 were observed in 15, 36 and 74 cases, respectively. Adenocarcinomas expressed higher levels of the aforementioned proteins as compared with squamous cell carcinomas (p-value < 0.05). Moreover, a statistically significant association was found between VEGF-A and CD31 expression levels (p-value = 0.006).ConclusionsOur study was the first to investigate the associations between GRP78 and the angiogenesis markers CD31 and VEGF-A in NSCLC patients. High GRP78 expression was revealed in the majority of the investigated samples. Nevertheless, no relationship was found between GRP78 and VEGF-A or CD31 which could be attributed to small sample size. On the other hand, the positive association between VEGF-A and CD31 expression levels suggests that VEGF-A may cooperate with CD31 to promote angiogenesis in NSCLC.

Download Full-text

Expression and Significance of HPV16 E6/E7 mRNAs in the Bronchial Brush and TBNA Cells of Patients With Small Cell Lung Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211019505 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110195

Author(s):

Di-Jia Zou ◽

Ya-Bin Zhao ◽

Jing-Hua Yang ◽

Hong-Tao Xu ◽

Qing-Chang Li ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Central Type ◽

Expression Levels

Background and Objective: Small cell lung cancer (SCLC) is characterized by rapid growth, strong invasion, and early metastasis. However, the cause of its occurrence remains unclear. High-risk HPV infection is closely related to the occurrence of non-small cell lung cancer and cervical small cell neuroendocrine carcinoma. Methods: The expression levels of E6 mRNA and E7 mRNA in HPV16 were detected by qRT-PCR in the bronchial brushing and transbronchial needle aspiration (TBNA) of 310 patients with lung cancer and with benign lung diseases. To make the design of this experiment scientific and reasonable, the expression levels in lung squamous cell carcinoma were taken as positive controls, while those in benign cells were taken as negative controls. Results: The expression levels of E6 mRNA and E7 mRNA in SCLC group were significantly higher than those in benign cell group and slight higher than those in squamous cell carcinoma group. The expression levels of E6 mRNA and E7 mRNA in the central type of SCLC were significantly higher than those in the peripheral type of SCLC. Conclusions: We speculate that the occurrence of some small cell carcinoma is the same as that of some squamous cell carcinoma, which is closely related to HPV16 infection. The overexpression of E6 mRNA and E7 mRNA is in some benign lesion cells, which may be related to HPV transient infection.

Download Full-text

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200721130700 ◽

2020 ◽

Vol 20 (17) ◽

pp. 2074-2081

Author(s):

Onur Tokgun ◽

Pervin E. Tokgun ◽

Kubilay Inci ◽

Hakan Akca

Keyword(s):

Lung Cancer ◽

Stem Cell ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Therapeutic Strategy ◽

Small Cell ◽

Small Cell Lung ◽

Expression Levels ◽

Qrt Pcr ◽

Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

Download Full-text

A re-evaluation of squamous cell carcinoma antigen (SCC) as a serum marker for non-small cell lung cancer

Medical Oncology ◽

10.1007/s12032-007-9021-3 ◽

2007 ◽

Vol 25 (2) ◽

pp. 187-189 ◽

Cited By ~ 11

Author(s):

Katsunori Kagohashi ◽

Hiroaki Satoh ◽

Hiroichi Ishikawa ◽

Morio Ohtsuka ◽

Kiyohisa Sekizawa

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Serum Marker ◽

Small Cell ◽

Squamous Cell Carcinoma Antigen ◽

Small Cell Lung

Download Full-text

Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2009.346 ◽

2016 ◽

Vol 71 (4) ◽

Cited By ~ 1

Author(s):

T. Kontakiotis ◽

N. Manolakoglou ◽

F. Zoglopitis ◽

D. Iakovidis ◽

L. Sacas ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Northern Greece ◽

Female Ratio

Background and Aim. The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. Methods. From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. Results. Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8±9.4 vs. 62.1±8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. Conclusion. The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

Download Full-text

Identification of a Subset of Human Non–Small Cell Lung Cancer Patients with High PI3Kβ and Low PTEN Expression, More Prevalent in Squamous Cell Carcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-13-1638 ◽

2013 ◽

Vol 20 (3) ◽

pp. 595-603 ◽

Cited By ~ 17

Author(s):

Marie Cumberbatch ◽

Ximing Tang ◽

Garry Beran ◽

Sonia Eckersley ◽

Xin Wang ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Cancer Patients ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients

Download Full-text

Mutation profile of non-small cell lung cancer revealed by next generation sequencing

10.21203/rs.3.rs-23075/v2 ◽

2020 ◽

Author(s):

Ya-Sian Chang ◽

Siang-Jyun Tu ◽

Yu-Chia Chen ◽

Ting-Yuan Liu ◽

Ya-Ting Lee ◽

...

Keyword(s):

Lung Cancer ◽

Squamous Cell Carcinoma ◽

Small Cell Lung Cancer ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Targeted Therapies ◽

Small Cell ◽

Small Cell Lung ◽

Whole Exome

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.

Download Full-text

Identifying Cross-Scale Associations between Radiomic and Pathomic Signatures of Non-Small Cell Lung Cancer Subtypes: Preliminary Results

Cancers ◽

10.3390/cancers12123663 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3663

Author(s):

Charlems Alvarez-Jimenez ◽

Alvaro A. Sandino ◽

Prateek Prasanna ◽

Amit Gupta ◽

Satish E. Viswanath ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Density ◽

Squamous Cell ◽

Cell Lung Cancer ◽

Ct Images ◽

Small Cell ◽

Small Cell Lung ◽

Cancer Subtypes ◽

Initial Results

(1) Background: Despite the complementarity between radiology and histopathology, both from a diagnostic and a prognostic perspective, quantitative analyses of these modalities are usually performed in disconnected silos. This work presents initial results for differentiating two major non-small cell lung cancer (NSCLC) subtypes by exploring cross-scale associations between Computed Tomography (CT) images and corresponding digitized pathology images. (2) Methods: The analysis comprised three phases, (i) a multi-resolution cell density quantification to identify discriminant pathomic patterns for differentiating adenocarcinoma (ADC) and squamous cell carcinoma (SCC), (ii) radiomic characterization of CT images by using Haralick descriptors to quantify tumor textural heterogeneity as represented by gray-level co-occurrences to discriminate the two pathological subtypes, and (iii) quantitative correlation analysis between the multi-modal features to identify potential associations between them. This analysis was carried out using two publicly available digitized pathology databases (117 cases from TCGA and 54 cases from CPTAC) and a public radiological collection of CT images (101 cases from NSCLC-R). (3) Results: The top-ranked cell density pathomic features from the histopathology analysis were correlation, contrast, homogeneity, sum of entropy and difference of variance; which yielded a cross-validated AUC of 0.72 ± 0.02 on the training set (CPTAC) and hold-out validation AUC of 0.77 on the testing set (TCGA). Top-ranked co-occurrence radiomic features within NSCLC-R were contrast, correlation and sum of entropy which yielded a cross-validated AUC of 0.72 ± 0.01. Preliminary but significant cross-scale associations were identified between cell density statistics and CT intensity values using matched specimens available in the TCGA cohort, which were used to significantly improve the overall discriminatory performance of radiomic features in differentiating NSCLC subtypes (AUC = 0.78 ± 0.01). (4) Conclusions: Initial results suggest that cross-scale associations may exist between digital pathology and CT imaging which can be used to identify relevant radiomic and histopathology features to accurately distinguish lung adenocarcinomas from squamous cell carcinomas.

Download Full-text

Circ_MDM2_000139, Circ_ATF2_001418, Circ_CDC25C_002079, and Circ_BIRC6_001271 Are Involved in the Functions of XAV939 in Non-Small Cell Lung Cancer

Canadian Respiratory Journal ◽

10.1155/2019/9107806 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Haixiang Yu ◽

Lei Xu ◽

Zhengjia Liu ◽

Bo Guo ◽

Zhifeng Han ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Regulatory Network ◽

Family Members ◽

Enrichment Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Expression Levels ◽

Relative Expression

Background. The small molecule inhibitor XAV939 could inhibit the proliferation and promote the apoptosis of non-small cell lung cancer (NSCLC) cells. This study was conducted to identify the key circular RNAs (circRNAs) and microRNAs (miRNAs) in XAV939-treated NSCLC cells. Methods. After grouping, the NCL-H1299 cells in the treatment group were treated by 10 μM XAV939 for 12 h. RNA-sequencing was performed, and then the differentially expressed circRNAs (DE-circRNAs) were analyzed by the edgeR package. Using the clusterprofiler package, enrichment analysis for the hosting genes of the DE-circRNAs was performed. Using Cytoscape software, the miRNA-circRNA regulatory network was built for the disease-associated miRNAs and the DE-circRNAs. The DE-circRNAs that could translate into proteins were predicted using circBank database and IRESfinder tool. Finally, the transcription factor (TF)-circRNA regulatory network was built by Cytoscape software. In addition, A549 and HCC-827 cell treatment with XAV939 were used to verify the relative expression levels of key DE-circRNAs. Results. There were 106 DE-circRNAs (including 61 upregulated circRNAs and 45 downregulated circRNAs) between treatment and control groups. Enrichment analysis for the hosting genes of the DE-circRNAs showed that ATF2 was enriched in the TNF signaling pathway. Disease association analysis indicated that 8 circRNAs (including circ_MDM2_000139, circ_ATF2_001418, circ_CDC25C_002079, and circ_BIRC6_001271) were correlated with NSCLC. In the miRNA-circRNA regulatory network, let-7 family members⟶circ_MDM2_000139, miR-16-5p/miR-134-5p⟶circ_ATF2_001418, miR-133b⟶circ_BIRC6_001271, and miR-221-3p/miR-222-3p⟶circ_CDC25C_002079 regulatory pairs were involved. A total of 47 DE-circRNAs could translate into proteins. Additionally, circ_MDM2_000139 was targeted by the TF POLR2A. The verification test showed that the relative expression levels of circ_MDM2_000139, circ_CDC25C_002079, circ_ATF2_001418, and circ_DICER1_000834 in A549 and HCC-827 cell treatment with XAV939 were downregulated comparing with the control. Conclusions. Let-7 family members and POLR2A targeting circ_MDM2_000139, miR-16-5p/miR-134-5p targeting circ_ATF2_001418, miR-133b targeting circ_BIRC6_001271, and miR-221-3p/miR-222-3p targeting circ_CDC25C_002079 might be related to the mechanism in the treatment of NSCLC by XAV939.

Download Full-text