Squamous Tissues Research Articles

Anti-N-Methyl-D-Aspartate Receptor Encephalitis Associated with Ovarian Teratoma in South China-Clinical Features, Treatment, Immunopathology, and Surgical Outcomes of 21 Cases.

Objective To study the clinical characteristics and surgical outcomes of anti-NMDAR encephalitis and the immunopathology of associated teratomas. Methods Twenty-one patients were enrolled in this retrospective study, who were diagnosed with anti-NMDAR encephalitis with ovarian teratoma and admitted to two tertiary hospitals in South China from July 2014 to December 2019. The clinical data of patients were reviewed. Comparisons were made between the patients with different outcomes after surgery. Immunohistochemical analyses of associated ovarian teratomas were performed. Results The mean age of the patients was 24.33 ± 5.12 years. The peak seasons of disease onset were autumn and winter (30.61% and 32.65%). The symptoms could be divided into 8 categories, including psychiatric abnormalities, seizures, movement dysfunction, consciousness disorders, autonomic dysregulation, speech disturbance, central hypoventilation, and memory deficits. All patients developed four or more categories of symptoms within the first four weeks. Twelve patients (57.1%) had a maximum mRS of 5, and 11 patients (52.4%) were admitted to ICU. Twenty patients received surgery, and only 3 patients were diagnosed pathologically with immature ovarian teratomas, while the other 17 patients had mature ovarian teratomas. After surgery, 17 patients (85.0%) got clinical improvement. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. Immunohistochemical analysis revealed that there were NMDAR-positive neural tissues in all 8 teratomas and in which 3 cases also contained large numbers of NMDAR-positive sebaceous glands and squamous epithelial tissues. Conclusion The disease is of high prevalence in autumn and winter. The central hypoventilation symptom and mature ovarian teratomas were associated with surgical outcome. NMDAR-positive neural tissue is not the only etiological factor of encephalitis. We speculate that encephalitis development in some patients may result from NMDAR expression in sebaceous glands and squamous epithelial tissues.

Tratamento cirúrgico de frenectomia lingual: Relato de caso

Anquiloglossia, também conhecida popularmente como ¨língua presa¨ é uma anomalia congênita, definida como uma prega mediana localizada no dorso da língua e próximo ao assoalho bucal, que se estende até face lingual da crista alveolar. É constituído por pregas da membrana mucosa, tecido conjuntivo rico em fibras colágenas e elásticas, tecido gorduroso e fibras musculares, além de vasos sanguíneos protegidos por tecido epitelial pavimentoso estratificado. Tem a função de auxiliar na movimentação tridimensional da língua, deglutição, dicção e sucção. Nos casos de alterações congênitas, observa-se limitações dos movimentos linguais, interferências periodontais, ortodônticas, protéticas, além da socialização. A indicação cirúrgica geralmente é diagnosticada por dentistas, fonoaudiólogos e pediatras, podendo ser tratada cirurgicamente em qualquer idade através de técnicas convencionais e outras técnicas descritas na literatura, com auxílio de lâminas frias, eletrocautérios ou laser cirúrgico. O objetivo desse trabalho é relatar o caso de frenectomia lingual de um paciente do gênero masculino de 15 anos de idade.

Histological structure of the Tongue in Mongoose (Herpestes javanicus)

The aim of the present study was to investigate the histological structure of the tongue in Mongoose (Herpestes javanicus) and its related to the feeding pattern. Five adult animals were used in this study. The tongues were dissected and fixed in 10% formalin, then prepared by following stages (dehydration, clearing, and embedding). The serial section(5μ) were stained with(H&E) and some special stains. The histological examination showed that the tongue consists of three tunicae (mucosa, submucosa and musclaris) and the lining epithelium of the filiform papillae is composed of keratinized stratified squamous epithelial tissue. The cylindrical papillae are covered with a highly keratinized stratified squamous epithelial tissue, whereas the keratinized stratified squamous epithelium tissue is weakly keratinized at fungiform papillae, whilst circumvallate papillae are non-keratinized. The medullary of the papillae consists of a loose connective tissue which is considered as the lamina propria of the tongue, while the tunica submucosa consists of dense connective tissue. The muscularis is composed of skeletal muscle fibres arranged in three direction longitudinal, transverse and obliquate. The lingual glands(Von-Ebner and Weber) placed on both sides of the lingual root at the tunica submucosa and extend to the tunica muscularis. This study pointed out that the secretion of glands is mixed and the mucin is more neutral than acid.

Emerging importance of ACE2 in external stratified epithelial tissues

Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), has been identified as the receptor for the SARS-CoV-2. Several RAS components including ACE2 and its substrate Ang II are present in both eye and skin, two stratified squamous epithelial tissues that isolate organisms from external environment. Our recent findings in cornea and others in both skin and eye suggest contribution of this system, and specifically of ACE2 in variety of physiological and pathological responses of these organ systems. This review will focus on the role RAS system plays in both skin and cornea, and will specifically discuss our recent findings on ACE2 in corneal epithelial inflammation, as well as potential implications of ACE2 in patients with COVID-19.

The functional GRHL3-filaggrin axis maintains a tumor differentiation potential and influences drug sensitivity

Current therapies for treating heterogeneous cancers such as head and neck squamous cell carcinoma (HNSCC) are non-selective and are administered independent of response biomarkers. Therapy resistance subsequently emerges, resulting in increased cellular proliferation that is associated with loss of differentiation. Whether a cancer cell differentiation potential can dictate therapy responsiveness is still currently unknown. A multi-omic approach integrating whole-genome and whole-transcriptome sequencing with drug sensitivity was employed in a HNSCC mouse model, primary patients’ data, and human cell lines to assess the potential of functional differentiation in predicting therapy response. Interestingly, a subset of HNSCC with effective GRHL3-dependent differentiation was the most sensitive to inhibitors of PI3K/mTOR, c-Myc, and STAT3 signaling. Furthermore, we identified the GRHL3-differentiation target gene Filaggrin (FLG) as a response biomarker and more importantly, stratified HNSCC subsets as treatment resistant based on their FLG mutational profile. The loss of FLG in sensitive HNSCC resulted in a dramatic resistance to targeted therapies while the GRHL3-FLG signature predicted a favorable patient prognosis. This study provides evidence for a functional GRHL3-FLG tumor-specific differentiation axis that regulates targeted therapy response in HNSCC and establishes a rationale for clinical investigation of differentiation-paired targeted therapy in heterogeneous cancers.

Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in squamous cell lung cancer

Non-small cell lung cancer (NSCLC) targeted therapies are mostly based on activating mutations and rearrangements which are rare events in Lung Squamous Cell Carcinomas (LUSC). Recently advances in immunotherapy have improved the therapeutic repository for LUSC, but there is still an urgent need for novel targets and biomarkers. We examined 73 cases of LUSC for relative copy number amplification of DCUN1D1, BCL9, FGFR1 and ERBB2 genes and searched for correlations with molecular alterations and clinicopathological characteristics. In our cohort BCL9 gene was amplified in 57.5 % of the cases, followed by DCUN1D1 in 37 %, FGFR1 in 19 % whereas none of the cases were amplified in ERBB2 gene. The majority of the samples exhibited amplification in at least one gene while half of them displayed concurrent amplification of two/three genes. Interestingly, 93 % of the FGFR1 amplified cases were also found co amplified with DCUN1D1 and/or BCL9 genes. Linear correlations were found between BCL9 and DCUN1D1 as well as BCL9 and FGFR1 gene amplification. BCL9 and DCUN1D1 genes’ amplification was correlated with poorly differentiated tumors (p = 0.035 and p = 0.056 respectively), implying their possible role in tumor aggressiveness. This is the first study, to the best of our knowledge that examines the correlation of DCUN1D1 and BCL9 genes relative copy number amplification with molecular alterations and clinicopathologic characteristics of squamous cell lung cancer tissue samples. Our findings show concurrent amplification of genes in different chromosomes, with possible involvement in tumor aggressiveness. These results support the complexity of LUSC tumorigenesis and imply the necessity of multiple biomarkers / targets for a more effective therapeutic result in LUSC.

Gene expression of one important microRNA in blood and tissue samples of oral squamous cell carcinoma

Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most common oral malignancies, which accounts for 80-90% of malignant neoplasms of the oral cavity. MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by targeting mRNAs. Materials and Methods: In this case-control study, 40 patients with oral squamous cell carcinoma and 40 healthy individuals as control were studied. Blood samples were collected from both groups. Also, 30 cancer tissue samples and 30 healthy tissue samples were prepared and evaluated. RNA was extracted from collected peripheral blood and tissue samples and evaluated for the expression level of miR-494 via real-time PCR technique. P. value values<0.05 were considered statistically significant. Results: The expression level of miR-494 in serum (peripheral blood) of patients with oral squa- mous cell carcinoma increased by 1.12 fold (P-value<0.001) compared with healthy individuals. Also, the expression level of miR-494 in samples of oral squamous cell carcinoma infected tissue showed a 1.28-fold increase compared to healthy tissue. Conclusion: The results of this study indicate an increase in the expression level (up-regula- tion) of miR-494 in oral squamous cell carcinoma. This biomarker can be used in screening and early detection of oral squamous cell carcinoma.

Identification of differentially expressed proteins and clinicopathological significance of HMGB2 in cervical cancer

To investigate the complexity of proteomics in cervical cancer tissues, we used isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry analysis on a panel of normal cervical tissues (N), high-grade squamous intraepithelial lesion tissues (HSIL) and cervical cancer tissues (CC). Total 72 differentially expressed proteins were identified both in CC vs N and CC vs HSIL. The expression of HMGB2 was markedly higher in CC than that in HSIL and N. High HMGB2 expression was significantly correlated with primary tumor size, invasion and tumor stage. The up-regulated HMGB2 was discovered to be associated with human cervical cancer. These findings suggest that HMGB2 may be a potentially prognostic biomarker and a target for the therapy of cervical cancer.

Features of oral squamous cell carcinoma in ex vivo fluorescence confocal microscopy.

Real-time microscopic imaging of freshly excised oral squamous cell carcinomas (OSCCs) would be potentially supportive in rapid recognition of oral malignancy and an optimal and time-saving management of patients' surgical treatment. The aim of this study was to examine oral squamous cell cancer tissue in regards to the commonly known and well-described histomorphologic criteria for the diagnosis of OSCC in ex vivo confocal fluorescent microscopy and to analyze its correlation with grade of differentiation and level of invasiveness. Ex vivo confocal laser scanning microscopy (CLSM) images of 38 OSCCs were evaluated immediately after excision for presence or absence of various cytological and architectural features based on the histopathological background. Next, these features were compared to the grade of differentiation as elaborated via gold standard histologic examination. Of 38 invasive OSCCs, 14 were well differentiated, while three moderately and 19 were poorly differentiated. The presence of the commonly known cytologic and histopathologic criteria for the diagnosis of oral squamous cell carcinoma such as the destruction of the basal cell membrane, cellular and nuclear pleomorphism, anisocytosis, intraepithelial keratinization, nuclear hyperchromasia, atypical mitotic figures as well as the presence of necrosis, and mixed inflammation could be observed in ex vivo fluorescence confocal microscopy (FCM). In ex vivo fluorescence confocal microscopy pictures, cellular pleomorphism and anisocytosis were observed more often in poorly differentiated OSCCs. Intraepithelial keratinization was associated with well differentiated and moderately differentiated OSCCs. The results demonstrate the high potential of ex vivo fluorescence confocal microscopy in fresh tissue for rapid real-time diagnosis of OSCC.

CLINICAL STUDY TO EVALUATE THE EFFICACY OF AGNIKARMA IN KARNINI WITH SPECIAL REFERENCE TO CERVICAL EROSION

Women’s health is extremely valuable and source of healthy nation. There are so many diseases that affects quality of life of women; cervical erosion is one among them. On the basis of etiopathogenesis, clinical features, complications and principles of treatment; Karnini Yonivyapad is very near to cervical erosion. 'Karnini Yonivyapada' is a disease caused by vitiation of Vata and Kapha dosha while affected dhatu is Rakta. Treatment is aimed at Vata-Kaphashamaka and Raktashodhaka. In cervical erosion, there is replacement of squamous epithelium of ectocervix by columnar epithelium of endo cervical canal. Although it is a benign condition but ignorance of this disease may lead to infertility and cervical malignancy. The treatment of cervical erosion is designed to destruct the columnar epithelium and to promote the re-epithelization of the squamous tissues. Electric cauterization and laser are the standard treatment modalities of erosion in modern medical science which are the modified form of Agnikarma but so many side effect associated with them. In the present study, the management of cervical erosion was done through Agnikarma by Jamabbadan shalaka and found as better alternative in the management of Karnini (Cervical erosion).

MiR-449a-5p regulates the proliferation of esophageal carcinoma cell by targeting B-cell lymphoma 2.

BackgroundEsophageal cancer (EC) is a common malignancy that claims millions of lives globally each year. Impairment of esophageal carcinoma cell proliferation could provide a therapeutic approach to treating EC. MiR-449a-5p has been put forward as a crucial tumor suppressor in multiple cancers. In this study, we aimed to determine the mechanism underlying the regulating effect of miR-449a-5p on EC cell proliferation.MethodsThe level of miR-449a-5p in esophageal squamous cell carcinoma (ESCC) tissues and adjacent normal esophageal squamous tissues was detected using real-time polymerase chain reaction. The protein level of B-cell lymphoma 2 (Bcl-2) was measured by western blot. MTT and colony formation assays were carried out to assess Eca-109 cell proliferation.ResultsThe level of miR-449a-5p in ESCC tissues was reduced in comparison with that in adjacent normal tissues. Down-regulation of miR-449a-5p promoted the proliferation of ESCC cells. Bcl-2 was established as a target gene of miR-449a-5p, and its silencing resulted in the reversal of the effects of miR-449a-5p inhibitor on the proliferation of Eca-109 cells.ConclusionOverexpression of miR-449a-5p inhibited the proliferation of Eca-109 cells via negative regulation of Bcl-2.

Distinguishing Non-Small Cell Lung Cancer Subtypes in Fine Needle Aspiration Biopsies by Desorption Electrospray Ionization Mass Spectrometry Imaging.

Distinguishing adenocarcinoma and squamous cell carcinoma subtypes of non-small cell lung cancers is critical to patient care. Preoperative minimally-invasive biopsy techniques, such as fine needle aspiration (FNA), are increasingly used for lung cancer diagnosis and subtyping. Yet, histologic distinction of lung cancer subtypes in FNA material can be challenging. Here, we evaluated the usefulness of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to diagnose and differentiate lung cancer subtypes in tissues and FNA samples. DESI-MSI was used to analyze 22 normal, 26 adenocarcinoma, and 25 squamous cell carcinoma lung tissues. Mass spectra obtained from the tissue sections were used to generate and validate statistical classifiers for lung cancer diagnosis and subtyping. Classifiers were then tested on DESI-MSI data collected from 16 clinical FNA samples prospectively collected from 8 patients undergoing interventional radiology guided FNA. Various metabolites and lipid species were detected in the mass spectra obtained from lung tissues. The classifiers generated from tissue sections yielded 100% accuracy, 100% sensitivity, and 100% specificity for lung cancer diagnosis, and 73.5% accuracy for lung cancer subtyping for the training set of tissues, per-patient. On the validation set of tissues, 100% accuracy for lung cancer diagnosis and 94.1% accuracy for lung cancer subtyping were achieved. When tested on the FNA samples, 100% diagnostic accuracy and 87.5% accuracy on subtyping were achieved per-slide. DESI-MSI can be useful as an ancillary technique to conventional cytopathology for diagnosis and subtyping of non-small cell lung cancers.

Oncogenic LncRNA CASC9 in Cancer Progression.

Long non-coding RNAs (LncRNAs), with the length of over 200 nucleotides, that originate from intergenic, antisense, or promoter-proximal regions, are a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, firstly found its oncogenic function in esophageal cancer. In the following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, and the associated studies collected in systematic retrieval of PubMed used lncRNA and CASA9 as keywords. CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depressing cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 as closely related to the neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/ therapeutic potential of CASC9 in various human cancers. Long non-coding RNA CASC9 likely serve as useful disease biomarkers or therapeutic targets which be effectively applied in the treatment of different kinds of cancers.

A conditional mouse expressing an activating mutation in NRF2 displays hyperplasia of the upper gastrointestinal tract and decreased white adipose tissue.

Activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) transcription factor is a critical and evolutionarily conserved cellular response to oxidative stress, metabolic stress, and xenobiotic insult. Deficiency of NRF2 results in hypersensitivity to a variety of stressors, whereas its aberrant activation contributes to several cancer types, most commonly squamous cell carcinomas of the esophagus, oral cavity, bladder, and lung. Between 10% and 35% of patients with squamous cell carcinomas display hyperactive NRF2 signaling, harboring activating mutations and copy number amplifications of the NFE2L2 oncogene or inactivating mutations or deletions of KEAP1 or CUL3, the proteins of which co-complex to ubiquitylate and degrade NRF2 protein. To better understand the role of NRF2 in tumorigenesis and more broadly in development, we engineered the endogenous Nfe2l2 genomic locus to create a conditional mutant LSL-Nrf2E79Q mouse model. The E79Q mutation, one of the most commonly observed NRF2-activating mutations in human squamous cancers, codes for a mutant protein that does not undergo KEAP1/CUL3-dependent degradation, resulting in its constitutive activity. Expression of NRF2 E79Q protein in keratin 14 (KRT14)-positive murine tissues resulted in hyperplasia of squamous cell tissues of the tongue, forestomach, and esophagus, a stunted body axis, decreased weight, and decreased visceral adipose depots. RNA-seq profiling and follow-up validation studies of cultured NRF2E79Q murine esophageal epithelial cells revealed known and novel NRF2-regulated transcriptional programs, including genes associated with squamous cell carcinoma (e.g. Myc), lipid and cellular metabolism (Hk2, Ppard), and growth factors (Areg, Bmp6, Vegfa). These data suggest that in addition to decreasing adipogenesis, KRT14-restricted NRF2 activation drives hyperplasia of the esophagus, forestomach, and tongue, but not formation of squamous cell carcinoma. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The KEAP1/NRF2 Signaling Pathway in Keratinization.

Keratinization is a tissue adaptation, but aberrant keratinization is associated with skin disorders such as ichthyoses, atopic dermatitis, psoriasis, and acne. The disease phenotype stems from the interaction between genes and the environment; therefore, an understanding of the adaptation machinery may lead to a new appreciation of pathomechanisms. The KEAP1/NRF2 signaling pathway mediates the environmental responses of squamous epithelial tissue. The unpredicted outcome of the Keap1-null mutation in mice allowed us to revisit the basic principle of the biological process of keratinization: sulfur metabolism establishes unparalleled cytoprotection in the body wall of terrestrial mammals. We summarize the recent understanding of the KEAP1/NRF2 signaling pathway, which is a thiol-based sensor-effector apparatus, with particular focuses on epidermal differentiation in the context of the gene-environment interaction, the structure/function principles involved in KEAP1/NRF2 signaling, lessons from mouse models, and their pathological implications. This synthesis may provide insights into keratinization, which provides physical insulation and constitutes an essential innate integumentary defense system.

Abstract 2342: Tobacco exposure and somatic mutations in normal bronchial epithelia

Abstract Background Lung cancer is the leading cause of cancer death, of which 80-90% are attributed to tobacco smoking. Our understanding of how tobacco exposure affects mutational burden, mutational signatures, driver mutations and clonal dynamics in normal lung tissue is limited. Also, genetic differences between normal cells and cancer cells in lung has not been fully elucidated. Methods To access the landscape of somatic mutations in normal bronchial epithelia, we sequenced whole genomes of 632 single-cell-derived colonies of lung basal cells from 16 patients, including 3 children, 4 never-smokers, 6 ex-smokers and 3 current smokers. Five patients had squamous cell carcinomas or carcinoma in situ, which we also sequenced to compare the genetic alteration between normal and cancer cells. Results A positive correlation between the number of base substitutions and age was observed, and 22 somatic mutations accumulated per year (95% confidence interval:20-25; P=10−8). Previous or current smoking significantly increased mutational burden: 2330 substitutions in ex-smokers and 5300 in current smokers. In addition, tobacco smoking is massively increasing both between-subject and within-subject variance of mutation burden. A population of cells in subjects with smoking history had mutation burdens equivalent to that expected for never-smokers: these cells had less damage from tobacco-specific mutational processes, and were four-fold more frequent in ex-smokers than current smokers. Signature analysis revealed that the same mutational signatures seen in lung cancers operate both in patients with and without smoking history: endogeneous signatures, including COSMIC signatures 1 and 5, and APOBEC-related signatures. Three mutational signatures were largely restricted to current or ex-smokers, including known smoking-related COSMIC signature 4 characterized by C>A transversions, signature 16 characterized by T>C mutations with extremely strong transcription strand bias and a new signature characterized by T>A and T>C mutations. dN/dS method identified driver genes in normal bronchial epithelium, including NOTCH1, TP53 and FAT1, which were overlapped with those seen in squamous cell lung cancers and other normal squamous tissues such as esophagus and skin. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged never-smokers. In current smokers, ≥25% of cells carried driver mutations and 0-6% cells had 2 or even 3 drivers. Layering driver mutations onto phylogenetic trees revealed that driver mutations occurred in early life. Compared to the normal bronchial epithelial cells, lung cancers and precancerous lesions were characterized by extensive copy number changes or structural variants and distinct set of driver mutations. Conclusions Tobacco smoking increases mutation burden, cell-to-cell heterogeneity and driver mutations. Our data of genetic lesions in normal bronchial cells provides insights into genetic alterations that drive carcinogenesis in lung. Citation Format: Kenichi Yoshida, Kate HC Gowers, Henry Lee-Six, Deepak P. Chandrasekharan, Tim Coorens, Elizabeth F. Maughan, Kathryn Beal, Andrew Menzies, Fraser R. Millar, Elizabeth Anderson, Sarah E. Clarke, Adam Pennycuick, Ricky M. Thackeray, Colin R. Butler, Nobuyuki Kakiuchi, Tomonori Hirano, Robert E. Hynds, Michael R. Stratton, Inigo Martincorena, Sam M. Janes, Peter J. Campbell. Tobacco exposure and somatic mutations in normal bronchial epithelia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2342.

MiR-106a Regulates Cell Proliferation and Autophagy by Targeting LKB1 in HPV-16-Associated Cervical Cancer.

miR-106a is aberrantly regulated in various tumors and plays an important role in carcinogenesis. However, the biological role and molecular mechanism by which miR-106a contributes to cervical squamous cell carcinoma (CSCC) remains elusive. In this study, we verified that miR-106a was elevated in both human papilloma virus (HPV) 16-positive CSCC tissues and cell lines. ROC curve analysis showed that miR-106a could well distinguish HPV-16-positive CSCC tissues from normal cervical squamous epithelium tissues. High expression of miR-106a was associated with malignant clinicopathologic parameters in CSCC tissues. Exogenous expression of miR-106a greatly promoted cervical cancer cell proliferation while attenuated autophagy. Furthermore, a novel target of miR-106a, liver kinase B1 (LKB1), a proven tumor suppressor in cervical cancer was verified. Here we confirmed LKB1 was negatively correlated with malignant clinicopathologic parameters in CSCC tissues. Overexpression of LKB1 neutralized the effect of miR-106a on proliferation and autophagy in cervical cancer cell lines. In addition, the role of miR-106a in cell proliferation and autophagy was via LKB1 and its downstream pathway AMP-activated protein kinase-mammalian target of rapamycin. Of note, miR-106a was upregulated by HPV-16 E7 protein. The function of HPV-16 E7 to cell proliferation was suppressed when knockdown miR-106a in HPV-16 E7-expressing cells. IMPLICATIONS: Our study highlights the tumorigenic role and regulatory mechanism of miR-106a in CSCC. miR-106a may be a potential therapeutic target in HPV-associated cervical cancer.

Application of immune cell infiltration in the diagnosis and prognosis of non-small cell lung cancer

Immune cell infiltration is of great significance for the diagnosis and prognosis of cancer. In this study, we collected gene expression data of non-small cell lung cancer (NSCLC) and normal tissues included in TCGA database, obtained the proportion of 22 immune cells by CIBERSORT tool, and then evaluated the infiltration of immune cells. Subsequently, based on the proportion of 22 immune cells, a classification model of NSCLC tissues and normal tissues was constructed using machine learning methods. The AUC, sensitivity and specificity of classification model built by random forest algorithm reached 0.987, 0.98 and 0.84, respectively. In addition, the AUC, sensitivity and specificity of classification model of lung adenocarcinoma and lung squamous carcinoma tissues constructed by random forest method 0.827, 0.75 and 0.77, respectively. Finally, we constructed a prognosis model of NSCLC by combining the immunocyte score composed of 8 strongly correlated features of 22 immunocyte features screened by LASSO regression with clinical features. After evaluation and verification, C-index reached 0.71 and the calibration curves of three years and five years were well fitted in the prognosis model, which could accurately predict the degree of prognostic risk. This study aims to provide a new strategy for the diagnosis and prognosis of NSCLC based on the classification model and prognosis model established by immune cell infiltration.

Polarization gating technique extracts depth resolved fluorescence redox ratio in oral cancer diagnostics.

Mortality of oral cancer is often due to late diagnosis. Effective non-invasive diagnostic techniques may increase the survival rate based on an earlier diagnosis.. We report on the application of the polarization gating technique for isolating weakly scattered and highly scattered components of fluorescence emission from the superficial and deeper layers of tissue due to intrinsic fluorophores NADH and FAD. The fluorescence polarization spectra were collected from 21 normal and 67 oral squamous cell carcinoma biopsy tissues. The tissues were excited at 350 nm and the fluorescence emission had two peaks corresponding to NADH, and FAD respectively. The spectra were analyzed using the polarization gating technique along with the spectral deconvolution method to derive the optical redox ratio from different layers of tissue. The fractional change in redox ratio between superficial and deeper layers of tissue exhibits excellent statistical significance (p<10-3) which may be due to a shift in the metabolic pathway from oxidative phosphorylation to glycolysis in the cancer cell. Further, variation in collagen intensity in deeper layers of tissue is observed which may be attributed to the breakdown of collagen fibers in the stroma. Linear discriminant analysis showed that oral cancer tissue is discriminated with a better accuracy using polarization gating technique than that of conventional fluorescence spectroscopy.

POLE2 Serves as a Prognostic Biomarker and Is Associated with Immune Infiltration in Squamous Cell Lung Cancer.

BackgroundSquamous cell lung cancer is the main cause of cancer-associated mortality. The discovery of promising prognostic biomarkers for predicting the survival of patients with squamous cell lung cancer remains a challenge.Material/MethodsGene expression profiles of GSE33479 and GSE51855, including 42 squamous cell lung cancer tissues and 17 normal tissues, from the GEO database were assessed to find common differentially expressed genes (DEGs) via the GEO2R online tool and Venn diagram software. Then, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were conducted. The key protein-protein interaction (PPI) network within those common DEGs was subsequently illustrated through a combination of Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape software. Finally, core genes associated with survival and levels of immune infiltration were demonstrated by the Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) online database, respectively.ResultsIn total, 483 DEGs were involved, including 216 upregulated genes enriched in “cell division”, “DNA replication”, and “DNA repair pathway” and 267 downregulated genes enriched in “cell adhesion”, “oxidation-reduction process”, and “cell-cell signaling”. The 75 core genes were selected by Molecular Complex Detection applied in Cytoscape. Four genes – MND1, FOXM1, CDC6, and POLE2 – were found to be significantly associated with survival. Further analysis of the KEEG pathway and TIMER database revealed that only POLE2 was enriched in “DNA replication” and its higher expression was negatively associated with survival and immune infiltration.ConclusionsHigher expression of POLE2 is a prognosis-related biomarker for worse survival and is negatively associated with immune infiltration in squamous cell lung cancer.