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Purpose To develop models to predict programmed death ligand 1 (PD-L1) expression in pulmonary squamous cell carcinoma (SCC) using CT. Materials and Methods A total of 97 patients diagnosed with SCC who underwent PD-L1 expression assay were included in this study. We performed a CT analysis of the tumors using pretreatment CT images. Multiple logistic regression models were constructed to predict PD-L1 positivity in the total patient group and in the 40 advanced-stage (≥ stage IIIB) patients. The area under the receiver operating characteristic curve (AUC) was calculated for each model. Results For the total patient group, the AUC of the 'total significant features model' (tumor stage, tumor size, pleural nodularity, and lung metastasis) was 0.652, and that of the 'selected feature model' (pleural nodularity) was 0.556. For advanced-stage patients, the AUC of the 'selected feature model' (tumor size, pleural nodularity, pulmonary oligometastases, and absence of interstitial lung disease) was 0.897. Among these factors, pleural nodularity and pulmonary oligometastases had the highest odds ratios (8.78 and 16.35, respectively). Conclusion Our model could predict PD-L1 expression in patients with lung SCC, and pleural nodularity and pulmonary oligometastases were notable predictive CT features of PD-L1. [ABSTRACT FROM AUTHOR]

Background and objective There is a high morbidity, mortality, and poor clinical prognosis of lung squamous cell carcinoma (LUSC). However, there is currently no effective targeted treatment plan for LUSC. As a long non-coding RNA (lncRNA), lncRNA miR143HG has been proven to play an important role in the occurrence and development of various tumors. However, the biological role played by lncRNA miR143HG in LUSC cells is still unclear. Therefore, this study aimed to investigate the mechanism of lncRNA miR143HG on regulating the biological behavior of LUSC H520 cells. Methods Pan-cancer analysis and differential expression analysis of lncRNA miR143HG were performed based on The Cancer Genome Atlas (TCGA) database. The predictive effect of lncRNA miR143HG on the diagnosis and prognosis of LUSC was evaluated by adopting the receiver operating characteristic (ROC) curve and timeROC curve. The enrichment degree of each pathway to lncRNA miR143HG was determined. The expression of lncRNA miR143HG and miR-155 in BEAS-2B cells and H520 cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR). H520 cells were randomly divided into blank control group (without any treatment), negative control group (transfected with lncRNA-NC), lncRNA miR143HG group (transfected with lncRNA miR143HG), and lncRNA miR143HG+miR-155 group (co-transfected with lncRNA miR143HG and miR-155). The approaches of CCK-8, wound healing test, Transwell assay, flow cytometry, qRT-PCR, and Western blot were respectively employed to detect the cell proliferation ability, cell migration ability, cell invasion ability, cell apoptosis rate, and expression level of related genes and proteins of the Wnt/β-Catenin pathway. Results The results of pan-cancer analysis and differential analysis collectively showed that except for renal clear cell carcinoma, the expression of lncRNA miR143HG in other cancer tissues was higher than that in healthy tissues, and the differences were significant in LUSC. The evaluation results of the ROC curve and timeROC curve suggested that lncRNA miR143HG was of great significance in the prediction of diagnosis and prognosis of LUSC. The pathways enriched in high expression of lncRNA miR143HG mainly included focal adhesion, vascular smooth muscle contraction, calcium signaling pathways, and so on; the pathways enriched in the low expression of lncRNA miR143HG embraced oxidative phosphorylation, cell cycle, basic transcription factors, etc. The qRT-PCR results showed that lncRNA miR143HG was low expressed but miR-155 was highly expressed in H520 cells when compared to BEAS-2B cells (P<0.05). Compared with the negative control group, the expression levels of the gene of lncRNA miR143HG, the gene and protein of Wnt, as well as the gene and protein of β-Catenin were significantly increased, while the gene expression of miR-155, the ability of cell proliferation, cell migration, and cell invasion were significantly reduced, but the cell apoptosis rate was dominantly elevated in cells of lncRNA miR143HG group (P<0.05). In addition, compared with the lncRNA miR143HG group, overexpression of miR-155 could reverse the biological behavior mediated by lncRNA miR143HG, and the difference was statistically significant (P<0.05). Conclusion LncRNA miR143HG was of great significance for the biological behavior of H520 cells. LncRNA miR143HG inhibited the ability of proliferation, migration, and invasion, as well as enhanced the apoptosis of H520 cells by downregulating miR-155 expression, which may be related to the Wnt/β-Catenin pathway. [ABSTRACT FROM AUTHOR]

Dysregulated expression of ubiquitin-specific protease 43 (USP43) has been recently discovered in malignancies. This study aimed to investigate the expression pattern of USP43 protein in lung squamous cell carcinoma (LUSC) and to explore its correlation with patients' clinicopathological characteristics as well as clinical outcomes. Expression of USP43 protein was determined by immunohistochemistry staining in a retrospective cohort containing 157 LUSC cases who underwent curative surgery in our hospital. Accordingly, USP43 protein was positively correlated with tumor size, depth of invasion, and lymph node metastasis. Patients with increased USP43 expression or positive lymph nodes exhibited a poorer overall survival. In addition, cellular assays elucidated that USP43 can promote LUSC growth and invasion. Taken together, our study demonstrated that USP43 may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the survival prediction and treatment of LUSC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the mechanism of LncRNA FAM201A mediating lung squamous cell carcinoma progression through interaction with miR-101. PATIENTS AND METHODS: NCI-H520 cells and SK-MES-1 cells were transfected with miRNA-101-mimics and miRNA-101-inhibitor, the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect FAM201A and miR-101 expression. CCK-8, Wound healing assay and transwell assay were utilized to detect the influence of FAM201A on the malignancy of NCI-H520NCI-H520 and SK-MES-1SKMES-1 cells. Cell apoptosis was determined by flow cytometry. The underlying pathways of FAM201A were measured using Western blot. Xenograft tumor experiments were conducted to detect tumor growth and metastasis in vivo.NCIH520SK-MES-1 Kaplan-Meier method calculated patient survival. RESULTS: (1) Silencing of FAM201A inhibited the proliferation, migration and invasion of NCI-H520 and SK-MES-1cells and stimulated cell apoptosis significantly. Furthermore, FAM201A elimination hindered tumor growth and metastasis in vivo. (2) Compared with the si-control group, the protein expression of Ki67, Vimentin, Cleaved-caspase-3 and N-cadherin were decreased in the si-FAM201A group. (3) After transfection of miR-101-mimics, the expression level of Vimentin protein was significantly increased, while the expression level of Vimentin protein was significantly decreased after miR-101-inhibitor transfection. (4) MiR-101 mimics could alleviate FAM201A silencing-induced inhibitive effects on cell proliferation, migration, invasion and promotive effects on cell apoptosis. CONCLUSIONS: FAM201A could target miR-101 and upregulate Vimentin to inhibit lung cancer progression. FAM201A was expected to be a potential biomarker and therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) usually shows expansive growth with large tumor nests; few reports on invasive growth patterns (INF) in LUSC have been associated with poor prognosis in gastrointestinal and urothelial cancers. In this study, we examine the association between INF and the prognosis of LUSC. We analyzed INF as a potential prognostic factor in 254 consecutive patients with LUSC who underwent complete surgical resection at our hospital between 2008 and 2017. INF was classified into 3 categories based on the structure of the tumor other than the large round solid nest of tumor cells. INF was categorized as INFa in 59 patients (23 %) with only well-demarcated large solid tumor cell nests, INFb in 89 patients (35 %) with medium to small, alongside large solid nests, and INFc in 98 patients (39 %) with cord-like/small nests or isolated cells plus large or medium solid nests. No significant lymph node metastasis differences were observed between INFc and INFa/b tumors. However, in patients with p-stage I, INFc had a poorer prognosis with regard to recurrence-free survival (RFS), with a 5-year RFS rate of 53.3 %, compared to 74.9 % for INFa/b (p = 0.010). Our study highlights a novel pathological concept of INF in LUSC, and contributed to the proposal that it is a factor indicating an unfavorable prognosis in patients with early-stage LUSC. A prospective multicenter study is warranted for INFc patients, as careful follow-up and adjuvant chemotherapy might lead to the early detection and prevention of recurrence. • INFc was associated with an unfavorable prognosis in patients with p-stage I surgically resected LUSC according to multivariable analysis. • INFc was strongly associated with visceral pleural invasion, vascular invasion, and lymphatic permeation, though lymphovascular invasion was frequent in INFa/b. • INFc tended to be more frequently associated with distant metastasis than INFa/b in the analysis of recurrence patterns. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA‐126‐3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA‐126‐3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real‐time PCR (RT‐qPCR). Associations between miRNA‐126‐3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA‐126‐3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT‐qPCR, and integration analysis consistently reported low expression of miRNA‐126‐3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA‐126‐3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA‐126‐3p may play a role in promoting the development of LUSC and miRNA‐126‐3p may be a biomarker for LUSC early diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The study aims to construct a multi-gene risk scoring model that can be used to predict the prognosis of patients with lung squamous cell carcinoma (LUSC). PATIENTS AND METHODS: RNA-seq data from 494 LUSC tumor samples and 49 peripheral lung tissue samples were obtained from TCGA_ LUSC database. Differential analysis was conducted using edgeR to screen differentially expressed lncRNAs (DElncRNAs) between LUSC and normal samples. Univariate Cox regression analysis was used to screen lncRNAs that were significantly correlated with LUSC prognosis. LASSO regression model was built to reduce complexity. The LUSC prognostic model based on lncRNAs was established by multivariate Cox regression analysis, which was evaluated by ROC curves and survival analysis. ROC and Kaplan-Meier survival curves of each lncRNA in the model were plotted and compared. RESULTS: 2085 DElncRNAs were identified. Combined with univariate Cox regression analysis, 342 prognosis-related genes were screened. After LASSO regression analysis, 11 lncRNAs tightly related to LUSC prognosis were identified and a risk scoring model was constructed. ROC curve analysis proved the good performance of the model. The Kaplan-Meier survival curve showed that the mortality in highrisk group was significantly higher. The survival analysis results of each lncRNA were also consistent with the prediction in Cox regression. CONCLUSIONS: Our results suggested that the 11-lncRNA risk scoring model may provide a new insight for predicting prognosis of LUSC patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Long noncoding RNA (lncRNA) family with sequence similarity 201-member A (FAM201A) is a novel lncRNA promoting the development of various cancers. However, the biological function of FAM201A on the metastasis of lung squamous cell carcinoma (LSCC) remains unknown. The aim of this study was to explore the molecular mechanism of FAM201A and its target protein in advanced LSCC. PATIENTS AND METHODS: Quantitative Polymerase Chain Reaction (qPCR) was applied to evaluate FAM201A expression in lung cancer tissues. The impact of high FAM201A expression on the overall survival in patients with lung cancer was tested using the log-rank test. The relevance between aberrant FAM201A and clinicopathological characteristics in patients with lung cancer was analyzed using the Chi-square tests. Cell proliferation was assayed using the Cell Counting Kit-8 (CCK-8) and a transwell assay, and the mice xenograft models were applied to determine the promoting effects of FAM201A on LSCC in vitro and in vivo. The underlying regulatory mechanism was explored through RNA transfection, qPCR, and Western blotting. The correlation between ATP-binding cassette transporter E1 (ABCE1) and FAM201A expression was verified using Spearman's correlation coefficient. RESULTS: FAM201A is aberrantly elevated in tissues from patients with non-small cell lung cancer. High levels of FAM201A expression were more likely to present in patients with squamous type, M1 stage, and inferior overall survival. Differential expression was found between non-metastatic and metastatic squamous carcinoma, but not in adenocarcinoma. FAM201A knockdown inhibits cell proliferation, migration, and invasion of LSCC cells in vitro, and represses tumor growth in vivo. Furthermore, ABCE1 in LSCC cells was downregulated by silencing FAM201A. The tissue level of ABCE1 was positively correlated with FAM201A expression in patients with LSCC. CONCLUSIONS: FAM201A may markedly induce migration and invasion of LSCC, resulting in the M1 stage and poor survival. These findings suggest the FAM201A-ABCE1 axis as a novel therapeutic target in LSCC. [ABSTRACT FROM AUTHOR]

Abstract Background There is currently no definite clinical implication for the subtypes of lung squamous cell carcinoma according to the 2015 WHO classification. This study aimed to investigate postoperative recurrence of the two major subtypes of lung squamous cell carcinoma: keratinizing squamous cell carcinoma (KSCC) and nonkeratinizing squamous cell carcinoma (NKSCC). Methods We identified the patients with KSCC and NKSCC who had undergone complete resection in Shanghai Chest Hospital between April 2015 and June 2016. Disease-free survival (DFS) was compared using Kaplan-Meier statistical analysis. Variables selected by univariate analysis were evaluated in multivariate analysis using the Cox proportional hazard model. Results A total of 334 patients included 231 (69.2%) cases with KSCC and 103 (30.8%) cases with NKSCC. There were more smokers in keratinizing than nonkeratinizing subtype (84.8% versus 72.8%, p = 0.009). The percentage of stage Ⅲ was higher in NKSCC than that in KSCC (35% versus 22.9%, p = 0.012). The 2-year DFS rates of stage Ⅰ, stage Ⅱ and stage Ⅲ were 90.1%, 66.4% and 37.7% in KSCC, 83.3%, 67.7% and 52.8% in NKSCC, respectively. There were no significant differences of 2-year DFS rates between KSCC and NKSCC. Furthermore, KSCC and NKSCC had no significant differences in recurrence patterns and metastatic sites. Conclusion There were no significant differences of postoperative recurrence between KSCC and NKSCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Using data from The Cancer Genome Atlas (TCGA), we aimed to explore the association between Egl nine homolog 1 (EGLN1/PHD2) expression and survival outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. PATIENTS AND METHODS: A retrospective study was conducted based on the level-3 data in the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC and data from the Human Protein Atlas (HPA). RESULTS: Both LUAD and LUSC had elevated PHD2 expression compared to their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that the high PHD2 expression LUAD patients had a significantly shorter overall survival (OS) and recurrence-free survival (RFS) (p=0.001 and p<0.001) compared to the low expression group. However, these differences were not observed in LUSC patients. Univariate and multivariate analysis showed that high PHD2 expression was an independent indicator of unfavorable OS (HR: 1.685, 95%CI: 1.251-2.269, p=0.001) and unfavorable RFS (HR: 2.008, 95%CI: 1.430-2.818, p<0.001) in LUAD patients. The methylation status of two CpG sites (cg07040244 and cg21875980) in PHD2 was at least moderately and negatively correlated with PHD2 expression. High methylation level of these two CpG sites was associated with better OS in LUAD patients. CONCLUSIONS: Elevated PHD2 expression might only serve as a valuable biomarker of poor prognosis in LUAD, but no in LUSC. Cg07040244 and cg21875980 might be two CpG sites modulating PHD2 expression in LUAD.OBJECTIVE: Using data from The Cancer Genome Atlas (TCGA), we aimed to explore the association between Egl nine homolog 1 (EGLN1/PHD2) expression and survival outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. PATIENTS AND METHODS: A retrospective study was conducted based on the level-3 data in the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC and data from the Human Protein Atlas (HPA). RESULTS: Both LUAD and LUSC had elevated PHD2 expression compared to their respective adjacent normal tissues. However, Kaplan-Meier survival curves showed that the high PHD2 expression LUAD patients had a significantly shorter overall survival (OS) and recurrence-free survival (RFS) (p=0.001 and p<0.001) compared to the low expression group. However, these differences were not observed in LUSC patients. Univariate and multivariate analysis showed that high PHD2 expression was an independent indicator of unfavorable OS (HR: 1.685, 95%CI: 1.251-2.269, p=0.001) and unfavorable RFS (HR: 2.008, 95%CI: 1.430-2.818, p<0.001) in LUAD patients. The methylation status of two CpG sites (cg07040244 and cg21875980) in PHD2 was at least moderately and negatively correlated with PHD2 expression. High methylation level of these two CpG sites was associated with better OS in LUAD patients. CONCLUSIONS: Elevated PHD2 expression might only serve as a valuable biomarker of poor prognosis in LUAD, but no in LUSC. Cg07040244 and cg21875980 might be two CpG sites modulating PHD2 expression in LUAD. [ABSTRACT FROM AUTHOR]

Background and objective 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 (P<0.001), promote cell apoptosis (P<0.001) and increase Caspase-3 enzyme activity (P<0.001). However, it has no effect on Caspase-8 enzyme activity (P>0.05). 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. Conclusion Microwave hyperthermia combined with gemcitabine remarkably inhibit the proliferation and induce apoptosis of human lung squamous cell carcinoma in vitro. This effect maybe associated with the activation of p53, cleavage of PARP protein, and induced the Caspase-3 dependent apoptosis. [ABSTRACT FROM AUTHOR]

Aims This study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma (LSCC) subtypes according to the 2015 WHO classification. Methods We identified 824 operable LSCC patients undergoing a complete surgical resection at Shanghai Chest Hospital between April 2015 and January 2017. Immunohistochemistry was used to investigate the clinicopathologic features. Results Among them, the percentages of LSCC subtypes were 66.1% (545/824), 28.6% (236/824), and 5.2% (43/824) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more males, more smokers, and more pneumonectomy surgeries in KSCC patients (p = 0.008, p = 0.000, p = 0.043). There were more N2 lymph node involvement and pathological stage III in NKSCC patients (p = 0.01, p = 0.03). BSCC did not demonstrate specificity to anything, but expressed adenocarcinoma markers more frequently. No significant difference existed between pathological subtypes and other clinicopathologic features, such as age, location type, visceral pleural involvement and lymphovascular invasion. The frequencies of EGFR sensitive mutations and ALK rearrangements were not significantly different among three subtypes. Conclusion Significant relationships exist between some clinicopathologic features and LSCC subtypes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the retinoic acid receptor-β (RAR-β) expression in lung squamous cell carcinoma (LSCC) tissues and its prognosis. PATIENTS AND METHODS: SP assay was used to detect the RAR-β expression in 100 cases of surgically resected LSCC tissues and 20 cases of peritumoral normal lung tissues, and prognosis follow-up was conducted. RESULTS: The overall positive expression rate of RAR-β was 54.00%, which was not correlated with age, gender, phase and pathological type (p>0.05). Stratified analysis showed that the prognosis of patients with positive IRAR-β expression in phase I was significantly better than that of those with negative IRAR-β expression, in which the median survival times were 31 and 22 months respectively (p=0.022). In contrast, the prognosis of patients with negative RAR-β expression was better than that of those with positive RAR-β expression in phase II and III A. The median survival times were 23 and 16 months respectively in phase II p = 0.008, and 19 and 7 months respectively in phase III A (p=0.019). CONCLUSIONS: RAR-β is expressed in LSCC tumor tissues. RAR-β expression, which is not significantly correlated with the clinicopathological characteristics of patients, affects the postoperative survival of LSCC patients in phase I and II-III A dually. RAR-β expression state is one of the independent factors for the prognosis of LSCC patients. [ABSTRACT FROM AUTHOR]

There have been advances in personalized therapy directed by molecular profiles in lung adenocarcinoma, but not in lung squamous cell carcinoma (SCC). The lack of actionable driver oncogenes in SCC has restricted the use of small-molecule inhibitors. Here, we show that SCC cell lines displayed differential sensitivities to belinostat, a pan-histone deacetylase inhibitor. Phosphoproteomic analysis of belinostat-treated SCC cells revealed significant downregulation of the MAPK pathway, along with the induction of apoptosis. In cisplatin-resistant cells that demonstrated aberrant MAPK activation, combined treatment with belinostat significantly inhibited cisplatin-induced ERK phosphorylation and exhibited strong synergistic cytotoxicity. Furthermore, belinostat transcriptionally upregulated the F-box proteins FBXO3 and FBXW10, which directly targeted son of sevenless (SOS), an upstream regulator of the MAPK pathway, for proteasome-mediated degradation. Supporting this, suppression of SOS/ERK pathway by belinostat could be abrogated by inhibiting proteasomal activity either with bortezomib or with siRNA knockdown of FBXO3/FBXW10. Taken together, these preclinical data offer a novel understanding of the epigenetic mechanism by which belinostat exerts its cytotoxicity and supports the combination with cisplatin in clinical settings for chemorefractory SCC tumors. [ABSTRACT FROM AUTHOR]

Background and objective OLC1 (overexpressed in lung cancer 1), screened out and cloned in our previous research, is a new gene associated with lung cancer. It is highly expressed in lung cancer and many other malignant tumors, and is associated with poor prognosis of esophageal squamous cell carcinoma, ovarian cancer, breast cancer and colorectal cancer. The aim of this research was to detect the expression level of OLC1 in the tumor tissues of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) and explore its relationship with the prognosis of lung cancer patients. Methods Lung cancer tissues of 108 SCC and 90 ADC was dealed with immunohistochemical staining to detect the expression level of OLC1. The relationship between the expression level of OLC1 and clinical parameters and prognosis was analyzed. Results The rate of high expression of OLC1 staining in ADC was significantly higher than that in SCC (87.5% vs 55.3%, P<0.001). The overexpression of OLC1 in tumor tissues did not have a significant relationship with the prognosis of patients with ADC, but it was related with a poor prognosis of SCC patients as the univariate analysis showed. However the multivariate regression analysis showed that correlation between the overexpression of OLC1 and poor prognosis of SCC patients did not have a statistical significance (P=0.05). Conclusion The expression of OLC1 in ADC might be higher than that in SCC. A higher score of OLC1 staining in tumor tissue was associated with a poorer prognosis of patients with SCC, but could not be an independent predictor for a shorter overall survival in patients with SCC. [ABSTRACT FROM AUTHOR]

Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study. The 831 genes (such as DSG3, PKP1, DSC3, TPX2, and UBE2C) were found upregulated and the 731 genes (such as ABCA8, SELENBP1, FAM107A, and CACNA2D2) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as EGFR, HRAS, JUN, CDH1, BRCA1, CASP3, RHOA, HDAC1, HIF1A, and CCNA2) were identified along with the eight gene modules that were significantly related to the protein–protein interaction (PPI). The clinical analyses identified that the overexpression group of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, LOX, and ITPA are substantially associated with a poor survival prognosis and the downregulated group of IL18R1 showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of CDH3, PLAU, PKP3, STIL, CALU, LOXL2, POSTN, DPP3, GALNT2, and ITPA were found in the TCGA LUSC cohort The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis. [ABSTRACT FROM AUTHOR]

Background and objective It has been proven that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and KRS are common driver genes in non-small cell lung cancer (NSCLC). Molecular targeted therapy increases the overall response rate and progression-free survival (PFS) of patients with EGFR-sensitive mutation or echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. However, target and targeted drugs for lung squamous cell carcinoma to indicate clinical therapy remain to be confrmed. The aim of this study was to analyze the relationship between the status of driver genes and the clinicopathologic characteristics of NSCLC. Methods A total of 90 patients were recruited and tested for EGFR, ALK and KRS mutations. The status of EGFR and KRS was tested by amplifcation refractory mutation system, and the status of ALK was tested by fuorescence in situ hybridization. Results Of the 90 patients, 8 patients had EGFR mutation (8.8%), and 2 cases had KRS mutation (2.2%). EML4-ALK fusion was found in 1 of 18 patients (5.6%). EGFR mutation occurred more frequently in females than in males (P=0.022). Significant differences were observed in pathological stage (P=0.042) and differentiation grade (P=0.003). No significant difference in PFS was observed between EGFR-TKI treatment and chemotherapy in EGFR mutation patients with squamous cell carcinoma of the lung (P=0.607). Patients with EML4-ALK fusion could beneft from targeted therapy. Conclusion EML4-ALK fusion occurred more frequently than EGFR and KRS mutations in patients with lung squamous cell carcinoma. Clinicopathologic characteristics were different between EGFR mutation and EGFR wild-type patients. The relationship between molecular targeted therapy and status of EGFR or ALK genes in patients with lung squamous cell carcinoma needs further investigation. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the correlation between proto-oncogene POK erythroid myeloid ontogenetic factor (Pokemon) and oncogene, mouse double minute 2 homolog (MDM2) in the carcinogenesis of lung squamous cell carcinoma in rats. Protein and messenger ribonucleic acid (mRNA) expressions of Pokemon and MDM2 in different stages of rat lung squamous cell carcinoma were measured using immunochemistry staining and in situ hybridization assays. Lung squamous cell carcinoma were viewed under the microscope in 60 rats (success rate: 80%) after treatment with carcinogen. Among these rats, 21 had bronchial epithelial hyperplasia, 13 had atypical hyperplasia, 28 had carcinoma in situ, 20 had invasive carcinoma and 16 had metastatic carcinoma. There were significant differences in the Pokemon and MDM2 expressions between the control group and the atypical hyperplasia group or squamous cell carcinoma group (p < 0.05). There were also significant differences of both genes between the non-metastatic carcinoma group and the metastatic carcinoma group (p < 0.05). Pokemon expression was positively correlated with MDM2 expression (r = 0.616, p = 0.000). These findings indicate that Pokemon and MDM2 were highly expressed in rat lungs following carcinogenesis in lung squamous cell carcinoma. The expression of Pokemon and MDM2 may contribute to the genesis and development of lung squamous cell carcinoma in rats. [ABSTRACT FROM AUTHOR]

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The purpose of this study aimed to figure out the role of GNA13 in lung squamous cell carcinoma (LUSC) and the underlying mechanism. Male BALB/c mice were used to construct LUSC mouse model. Cell growth was examined using MTT and colony formation assay. Cell migration and invasion was determined using wound healing and transwell assay. The expression and phosphorylation of protein was detected by Western blotting assay. Immunohistochemistry staining was used to observe the tumor growth and metastasis. GNA13 was overexpressed in both LUSC tissues and LUSC cell lines. Knockdown of GNA13 in LUSC cells reduced cell viability and inhibited the formation of colonies in the SK-MES-1 and NCI-H520 cells. Cell migration and invasion was also prevented by inhibition of GNA13 in the LUSC cells. Phosphorylation of PI3K and AKT was downregulated by silencing GNA13 and upregulated by overexpression of GNA13 in the LUSC cells. In LUSC mouse model, tumor size and tumor weight were significantly decreased in si-GNA13 mice compared to control group. The expression of GNA13, Ki67, MMP2 and phosphorylation of AKT were significantly inhibited in si-GNA13 mice compared to control group. This study has demonstrated that knockdown of GNA13 could inhibit cell survival, migration and metastasis in LUSC. • Expression of GNA13 was upregulated in lung squamous cell carcinoma. • Upregulation of GNA13 promoted cell proliferation, migration and invasion in lung squamous cell carcinoma. • Overexpression of GNA13 enhanced the activation of PI3K/AKT signaling pathway. • Knockdown of GNA13 inhibited tumor growth and metastasis in lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Summary: rohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P < .001), pathologic stage (P < .001), tumor size (P = .01), and lymph node metastasis (P = .004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P = .037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Summary: Forkhead box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes that are involved in cell proliferation, differentiation, and transformation by promoting both G1/S and G2/M transition. Although it has been reported that the FoxM1 signaling network is frequently deregulated with an up-regulated FoxM1 expression in human malignancies, the role of FoxM1 in lung cancer remains to be determined. We performed immunohistochemical detection of FoxM1 protein in 69 tissue samples from patients with primary pulmonary squamous cell carcinoma using a tissue microarray, and Western blotting was done to confirm the immunohistochemical observations. FoxM1 immunoreactivity was observed in 26 (37.7%) of the 69 squamous cell carcinoma cases. Analysis of the FoxM1 expression in 12 squamous cell carcinoma tissues and 2 normal lung tissues by Western blotting confirmed the immunohistochemical results. A FoxM1 expression was more frequently detected in the moderately or poorly differentiated squamous cell carcinomas than in the well-differentiated squamous cell carcinomas (P = .008). The tumors with a positive FoxM1 expression more frequently showed lymph node metastasis (P = .027) and an advanced American Joint Committee on Cancer stage (P = .049). The Kaplan-Meier survival curves demonstrated that patients with a positive FoxM1 expression had a significantly shorter survival time than those patients with a negative FoxM1 expression (P = .003). The multivariate analysis revealed that the FoxM1 expression was an independent poor prognostic factor (P = .018). A subset of pulmonary squamous cell carcinoma with a FoxM1 expression was associated with progressive pathologic features and an aggressive clinical course. [Copyright &y& Elsevier]

We set out to investigate whether transcriptome-based molecular subtypes in lung adenocarcinoma and lung squamous cell carcinoma are predictive of the response to programmed cell death 1 blockade. Molecular classification of non–small cell lung cancer was performed by unsupervised clustering of mRNA sequencing data from 87 lung adenocarcinoma and 101 lung squamous cell carcinoma specimens, and molecular subtypes were characterized according to their immunogenomic determinants. A prediction algorithm of molecular subtypes was applied to 35 patients with non–small cell lung cancer treated with programmed cell death 1 blockade to test its association with treatment response (GSE93157; the Barcelona cohort). Unsupervised hierarchical clustering of transcriptome sequencing data in lung adenocarcinoma and lung squamous cell carcinoma revealed 3 and 2 distinct clusters, respectively. Cluster 1 in each histology had a higher expression of immune regulatory molecules, increased cytolytic activity, higher interferon-γ signature, and more abundant infiltration of immune cells. Cluster 1 and other cluster(s) in lung adenocarcinoma and lung squamous cell carcinoma had immunologically-hot and immunologically-cold tumor-immune microenvironments, respectively. Immunologically-hot cluster 1 subtype is hereafter referred to as "good-tumor-immune microenvironments" and the other subtypes as "bad-tumor-immune microenvironments." The "good-tumor–immune microenvironments" subtype in lung adenocarcinoma included a high fraction of CD8 T cells and memory B cells, but a low fraction of regulatory CD4 T cells and tumor-associated myeloid cells. Forward and backward application of our molecular subtyping to the Barcelona cohort revealed that transcriptome-based molecular subtyping is significantly associated with response to programmed cell death 1 blockade. Molecular stratification by transcriptome sequencing data in non–small cell lung cancer identifies distinct immunomolecular subtypes that predict the response to programmed cell death 1 blockade. [ABSTRACT FROM AUTHOR]

Objectives MicroRNAs are a class of regulatory molecules involved in a wide variety of biological processes, including growth, development, and apoptosis. Given the widespread roles of microRNAs in biological processes, understanding their different expression profiles in normal, adjacent, and tumor tissues will provide insights into the consequences of aberrant expression. Methods With the use of next-generation deep sequencing technology, microRNA profiles in 3 pooled samples from normal, adjacent, and tumor tissues of 19 patients with lung squamous cell carcinoma were characterized comprehensively. Quantitative polymerase chain reaction was used to verify the primary findings in another 38 lung squamous cell carcinoma tumor samples. In situ hybridization also was performed for validation. Results A total of 368, 306, and 231 known microRNAs were identified from tumor, adjacent, and normal pooled samples, respectively, of which 40, 44, and 26 microRNAs displayed dysregulation with 2-fold or greater change in 3 compared groups of tumor versus normal, tumor versus adjacent, and adjacent versus normal, respectively. Sequencing data also showed that some coexpressed microRNAs displayed a pattern of progressive dysregulation. Some of the microRNAs exhibited consistent changes; among them, miR-425-5p and miR-218-5p were confirmed by quantitative polymerase chain reaction and in situ hybridization, and proved that the microRNA expression levels were closely related to tumor stages and sizes. It is suggested that some microRNAs, such as miR-425 and miR-183, might be a driver for tumor formation, growth, and progression to higher staging, whereas others, such as miR-218, might behave as a tumor suppressor in lung cancer. Functional annotation analysis indicated that the proteoglycan pathway in cancer and mitogen-activated protein kinase, Wnt, PI3K-Akt, and transforming growth factor-beta signaling pathways might be involved in the pathogenesis of lung squamous cell carcinoma. Conclusions This study describes the use of deep sequencing for comprehensive profiling of microRNAs in lung squamous cell carcinoma. The identified microRNA signatures may provide biomarkers for early detection, subclassification, and potential therapeutic targets of lung squamous cell carcinoma. This study also provides some insights into the molecular mechanism underlying the development and progression of lung squamous cell carcinoma, which may prove helpful for early diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]