Labeled-free quantitative proteomic analysis of cervical squamous cell carcinoma identifies potential protein biomarkers.

Background: Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of life. Thus, early diagnosis and further exploration into the pathogenesis of cervical cancer are crucial. Mass spectrometry technology is widely applied in clinical practice and can be used to further investigate the protein alterations during the onset of cervical cancer. Methods: Employing labeled-free quantitative proteomics technology and bioinformatics tools, we analyzed and compared the differential protein expression profiles between normal cervical squamous cell tissues and cervical squamous cell cancer tissues. GEPIA is an online website for analyzing the RNA sequencing expression data of tumor and normal tissue data from the TCGA and the GTEx databases. This approach aided in identifying qualitative and quantitative changes in key proteins related to the progression of cervical cancer. Results: Compared to normal samples, a total of 562 differentially expressed proteins were identified in cervical cancer samples, including 340 up-regulated and 222 down-regulated proteins. Gene ontology functional annotation, and KEGG pathway, and enrichment analysis revealed that the differentially expressed proteins mainly participated in metabolic pathways, spliceosomes, regulation of the actin cytoskeleton, and focal adhesion signaling pathways. Specifically, desmoplakin (DSP), protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L) and ANXA8 may be involved in cervical tumorigenesis by inhibiting apoptotic signal transmission. Moreover, we used GEPIA database to validate the expression of DSP, PPP1R13L and ANXA8 in human cancers and normal cervix. Conclusion: In this study, we identified 562 differentially expressed proteins, and there were three proteins expressed higher in the cervical cancer tissues. The functions and signaling pathways of these differentially expressed proteins lay a theoretical foundation for elucidating the molecular mechanisms of cervical cancer.

Acrokeratosis paraneoplastica (Basex syndrome) with trachyonychia preceding the diagnosis of squamous cell carcinoma of the lung.

Acrokeratosis paraneoplastica (Basex syndrome) is a rare paraneoplastic condition hallmarked by psoriasiform lesion development on acral surfaces, most often related to an underlying squamous cell carcinoma. Patients may also present with nail plate changes. Successful management of this condition can be accomplished by treating the underlying malignancy.

Integrating lipid metabolite analysis with MRI-based transformer and radiomics for early and late stage prediction of oral squamous cell carcinoma.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) presents significant diagnostic challenges in its early and late stages. This study aims to utilize preoperative MRI and biochemical indicators of OSCC patients to predict the stage of tumors. METHODS: This study involved 198 patients from two medical centers. A detailed analysis of contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) MRI were conducted, integrating these with biochemical indicators for a comprehensive evaluation. Initially, 42 clinical biochemical indicators were selected for consideration. Through univariate analysis and multivariate analysis, only those indicators with p-values less than 0.05 were retained for model development. To extract imaging features, machine learning algorithms in conjunction with Vision Transformer (ViT) techniques were utilized. These features were integrated with biochemical indicators for predictive modeling. The performance of model was evaluated using the Receiver Operating Characteristic (ROC) curve. RESULTS: After rigorously screening biochemical indicators, four key markers were selected for the model: cholesterol, triglyceride, very low-density lipoprotein cholesterol and chloride. The model, developed using radiomics and deep learning for feature extraction from ceT1W and T2W images, showed a lower Area Under the Curve (AUC) of 0.85 in the validation cohort when using these imaging modalities alone. However, integrating these biochemical indicators improved the model's performance, increasing the validation cohort AUC to 0.87. CONCLUSION: In this study, the performance of the model significantly improved following multimodal fusion, outperforming the single-modality approach. CLINICAL RELEVANCE STATEMENT: This integration of radiomics, ViT models, and lipid metabolite analysis, presents a promising non-invasive technique for predicting the staging of OSCC.

Unravelling the enigma: A rare case of primary gastric squamous cell carcinoma with aggressive metastasis.

This report details a rare case of squamous cell carcinoma (SCC) in the stomach, a condition accounting for only a fraction of gastric carcinomas. A 46-year-old male patient with dysphagia, abdominal pain, and haematemesis was diagnosed with primary gastric SCC displaying aggressive metastasis, an exceptionally low-incidence condition affecting mainly males in their sixth decade of life. Primary gastric SCC, though clinically similar to adenocarcinoma, involves a bleaker prognosis, lacking standardized treatment protocols. Histopathology and imaging confirmed the diagnosis, highlighting the challenges in managing advanced cases. Palliative chemotherapy showed partial remission but led to severe neuropathy. The case underscores the urgent need for research to understand the pathogenesis, effective management, and therapeutic targets for primary gastric SCC, emphasizing its scarcity and poor prognosis in medical literature. Increased clinical awareness and ongoing research are crucial for improving outcomes in such rare presentations.

Squamoid eccrine ductal carcinoma: clinical, histological and immunohistochemical features.

Squamoid eccrine ductal carcinoma (SEDC) is a cutaneous adnexal malignancy that is histologically challenging to distinguish from squamous cell carcinoma. We report three cases of this rare entity and review the present literature regarding clinical, histological, and immunohistochemical features. Patients presented with a single nodule or plaque lesion on their back and temple. The shave biopsies for Patient A and C were interpreted as SEDC. Patient B's initial shave biopsy was interpreted as probable surface of squamous cell carcinoma, and subsequent excision revealed SEDC. Ductal differentiation was confirmed by positive expression of epithelial membrane antigen and carcinoembryonic antigen immunostains in all three patients. Review of the 67 previously reported cases emphasizes the importance of diagnosing SEDC accurately and promptly given its potential for distant metastasis and mortality. Perineural or lymphatic invasion is associated with higher rate of recurrence or metastasis. There should be high pathologic suspicion for SEDC in an elderly patient presenting with a palpable lesion, even if located outside of the head and neck area, particularly when there is suggestion of ductal differentiation in a sample of a squamous neoplasm.

Transcriptomics analysis identified ezrin as a potential druggable target in cervical and gastric cancer cells.

OBJECTIVE: Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. METHODS: This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. RESULTS: EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. CONCLUSION: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.

An optical photothermal infrared investigation of lymph nodal metastases of oral squamous cell carcinoma.

In this study, optical photothermal infrared (O-PTIR) spectroscopy combined with machine learning algorithms were used to evaluate 46 tissue cores of surgically resected cervical lymph nodes, some of which harboured oral squamous cell carcinoma nodal metastasis. The ratios obtained between O-PTIR chemical images at 1252 cm-1 and 1285 cm-1 were able to reveal morphological details from tissue samples that are comparable to the information achieved by a pathologist's interpretation of optical microscopy of haematoxylin and eosin (H&E) stained samples. Additionally, when used as input data for a hybrid convolutional neural network (CNN) and random forest (RF) analyses, these yielded sensitivities, specificities and precision of 98.6 ± 0.3%, 92 ± 4% and 94 ± 5%, respectively, and an area under receiver operator characteristic (AUC) of 94 ± 2%. Our findings show the potential of O-PTIR technology as a tool to study cancer on tissue samples.

ETS1-mediated Regulation of SOAT1 Enhances the Malignant Phenotype of Oral Squamous Cell Carcinoma and Induces Tumor-associated Macrophages M2-like Polarization.

Oral squamous cell carcinoma (OSCC) is an aggressive cancer that poses a substantial threat to human life and quality of life globally. Lipid metabolism reprogramming significantly influences tumor development, affecting not only tumor cells but also tumor-associated macrophages (TAMs) infiltration. SOAT1, a critical enzyme in lipid metabolism, holds high prognostic value in various cancers. This study revealed that SOAT1 is highly expressed in OSCC tissues and positively correlated with M2 TAMs infiltration. Increased SOAT1 expression enhanced the capabilities of cell proliferation, tumor sphere formation, migration, and invasion in OSCC cells, upregulated the SREBP1-regulated adipogenic pathway, activated the PI3K/AKT/mTOR pathway and promoted M2-like polarization of TAMs, thereby contributing to OSCC growth both in vitro and in vivo. Additionally, we explored the upstream transcription factors that regulate SOAT1 and discovered that ETS1 positively regulates SOAT1 expression levels. Knockdown of ETS1 effectively inhibited the malignant phenotype of OSCC cells, whereas restoring SOAT1 expression significantly mitigated this suppression. Based on these findings, we suggest that SOAT1 is regulated by ETS1 and plays a pivotal role in the development of OSCC by facilitating lipid metabolism and M2-like polarization of TAMs. We propose that SOAT1 is a promising target for OSCC therapy with tremendous potential.

The Role of SCARA5 as a Potential Biomarker in Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing. In a previous study, we were able to show that the expression of THSD7A shows an association with unfavorable prognostic parameters in prostate cancer. There is also a link to a high expression of FAK. There is incidence that SCARA5 might be the downstream gene of THSD7A. Furthermore, there is evidence that SCARA5 interacts with FAK. We were interested in the role of SCARA5 as a potential biomarker in LSCC. Furthermore, we wanted to know whether SCARA5 expression is linked to THSD7A positivity and to the expression level of FAK. For this reason, we analyzed 101 LSCC tumors by immunohistochemistry. Tissue microarrays were utilized. No significant association was found between SCARA5 expression and overall survival or clinicopathological parameters. There was also no significant association between THSD7A positivity and SCARA5 expression level. Moreover, no significant association was found between FAK expression level and SCARA5 expression level. SCARA5 seems not to play a major role as a biomarker in squamous cell carcinoma of the lung.

Multi-Wavelength Raman Differentiation of Malignant Skin Neoplasms.

Raman microspectroscopy has become an effective method for analyzing the molecular appearance of biomarkers in skin tissue. For the first time, we acquired in vitro Raman spectra of healthy and malignant skin tissues, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), at 532 and 785 nm laser excitation wavelengths in the wavenumber ranges of 900-1800 cm-1 and 2800-3100 cm-1 and analyzed them to find spectral features for differentiation between the three classes of the samples. The intensity ratios of the bands at 1268, 1336, and 1445 cm-1 appeared to be the most reliable criteria for the three-class differentiation at 532 nm excitation, whereas the bands from the higher wavenumber region (2850, 2880, and 2930 cm-1) were a robust measure of the increased protein/lipid ratio in the tumors at both excitation wavelengths. Selecting ratios of the three bands from the merged (532 + 785) dataset made it possible to increase the accuracy to 87% for the three classes and reach the specificities for BCC + SCC equal to 87% and 81% for the sensitivities of 95% and 99%, respectively. Development of multi-wavelength excitation Raman spectroscopic techniques provides a versatile non-invasive tool for research of the processes in malignant skin tumors, as well as other forms of cancer.

[Nanocatalytic treatment of oral squamous cell carcinoma Cal 27 cells in vitro based on single-atom iron nanocatalysts].

PURPOSE: To prepare single-atom iron nanocatalysts(SAF NCs) and explore its efficacy on oral squamous cell carcinoma Cal 27 cells in vitro, and provide a new strategy for the treatment of oral squamous cell carcinoma. METHODS: SAF NCs were prepared with combination of isolation and pyrolysis, the microscopic characterization was observed by transmission electron microscopy, the morphology and chemical composition were analysed by X-ray diffractograms and elemental distribution energy spectroscopy. The catalytic properties were detected by TMB assay and electron spin resonance test, and finally the changes in the activity of Cal27 cells were observed by CCK-8, flow cytometry and confocal microscopy for in vitro treatment of oral squamous carcinoma, to investigate the therapeutic effect against Cal27 cells. Statistical analysis was performed with GraphPad Prism 9 software package. RESULTS: SAF NCs were successfully synthesized and characterized, which showed excellent catalytic properties at the solution level and good biocompatibility in in vitro cellular level. The viability of Cal27 cell was reduce to 32.08% after in vitro catalytic treatment under conditions mimicking the characteristics of the tumor microenvironment. CONCLUSIONS: Preliminary experiments demonstrated that SAF NCs with good biological properties could effectively inhibit the proliferation of Cal 27 cells in vitro, providing a new strategy for the treatment of oral squamous carcinoma.

Pterostilbene exerts anti-lung squamous cell carcinoma function by suppressing the level of KANK3.

Early detection of lung squamous cell carcinoma (LUSC) has a significant impact on clinical outcomes, and pterostilbene (PT) is a natural compound with promising anti-oncogenic activities. This study aimed to identify potential LUSC biomarkers through a series of bioinformatic analyses and clinical verification and explored the interaction between PT and selected biomarkers during the treatment of LUSC. The analysis of the expression profile of the clinical samples of LUSC was performed to identify dysexpressed genes (DEGs) and validated by IHC. The role of KANK3 in the anti-LUSC effects of PT was assessed with a series of in vitro and in vivo assays. 4335 DEGs were identified, including 1851 upregulated genes and 2484 downregulated genes. Survival analysis showed that KANK3 was significantly higher in patients with LUSC with an advanced tumor stage. In in vitro assays, PT suppressed cell viability, induced apoptosis, and inhibited migration and invasion in LUSC cell lines, which was associated with downregulation of KANK3. After the reinduction of the KANK3 level in LUSC cells, the anti-LUSC function of PT was impaired. In mice model, reinduction of KANK3 increased tumor growth and metastasis even under the treatment of PT. The findings outlined in the current study indicated that PT exerted anti-LUSC function in a KANK3 inhibition-dependent manner.

The impact of the tumor immune microenvironment and tumor-infiltrating lymphocyte subgroups on laryngeal cancer prognosis.

The absence of improvement in survival rates across various cancers, including laryngeal cancer, has led to an increasing interest in understanding the immune response to cancer. In head and neck cancers, immune modulatory mechanisms such as immune microenvironment and immune infiltration are important in cancer pathogenesis. This study aims to explore the distribution of tumor-infiltrating lymphocyte (TIL) subgroups in the immune microenvironment and evaluate their impact on tumor histopathological characteristics and prognosis. The study included 50 patients who underwent laryngectomy for laryngeal squamous cell carcinoma, in Istanbul University - Cerrahpasa, Faculty of Medicine Department of Otorhinolaryngology, between January 2016 and January 2018. Pathology specimens were evaluated using immunohistochemistry to assess the expressions of the CD3, CD20, CD8, CD4, CD25, and FoxP3 markers, identifying subgroups of TILs. The investigation aimed to uncover how these subgroups influence tumor histopathological features and survival outcomes. The high infiltration of CD3, CD20, and CD4 had a positive impact on disease-specific survival, disease-free survival, and recurrence-free survival. In addition, overall survival was positively affected by high CD3 and CD4 infiltrations. However, no significant relationship was observed between the expressions of CD8, FoxP3, and CD25 and any of the survival parameters. The infiltration of CD3, CD20, and CD4 positive cells indicative of a robust antitumoral immune response-emerged as favorable prognostic factors in laryngeal cancer. These findings suggest that enhancing the infiltration of CD3, CD20, and CD4 lymphocytes could be a therapeutic strategy worth exploring in clinical trials.

Oral Cavity Squamous Cell Carcinoma: Impact of Clear Margin Distance on Locoregional Control in Patients Undergoing Postoperative Radiotherapy.

INTRODUCTION: Postoperative radiotherapy can improve locoregional control (LC) in oral cavity squamous cell carcinoma (OCSCC) patients with positive resection margins. The present study aimed to evaluate the impact of surgical margin size on LC in this patient population. METHODS: This retrospective study involved 162 patients with OCSCC who underwent postoperative radiotherapy between 2000 and 2020 at the Department of Radiation Oncology, University Hospital Heidelberg and the German Cancer Research Center. The study aimed to determine the impact of different resection margins on LC, as well as overall survival (OS), progression-free survival (PFS), and treatment-related toxicity (CTCAE 4.03). RESULTS: Seventy-seven patients (47.5%) had involved (<1 mm) margins, 22 patients (13.6%) close (≤5 mm) margins, and 63 patients (38.9%) clear (>5 mm) margins. A surgical margin ≤ 5 mm was a significant predictor for worse LC (HR 2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2, 0.7, 2.0). CONCLUSION: Patients who have narrow resection margins (1-5 mm) experience poor local control and should receive postoperative radiotherapy. It is necessary to conduct further prospective studies to determine whether a narrower margin window could be achieved to better determine the appropriate indication for adjuvant radiotherapy.

Splicing Machinery Is Impaired in Oral Squamous Cell Carcinomas and Linked to Key Pathophysiological Features.

Alternative splicing dysregulation is an emerging cancer hallmark, potentially serving as a source of novel diagnostic, prognostic, or therapeutic tools. Inhibitors of the activity of the splicing machinery can exert antitumoral effects in cancer cells. We aimed to characterize the splicing machinery (SM) components in oral squamous cell carcinoma (OSCC) and to evaluate the direct impact of the inhibition of SM-activity on OSCC-cells. The expression of 59 SM-components was assessed using a prospective case-control study of tumor and healthy samples from 37 OSCC patients, and the relationship with clinical and histopathological features was assessed. The direct effect of pladienolide-B (SM-inhibitor) on the proliferation rate of primary OSCC cell cultures was evaluated. A significant dysregulation in several SM components was found in OSCC vs. adjacent-healthy tissues [i.e., 12 out of 59 (20%)], and their expression was associated with clinical and histopathological features of less aggressiveness and overall survival. Pladienolide-B treatment significantly decreased OSCC-cell proliferation. Our data reveal a significantly altered expression of several SM-components and link it to pathophysiological features, reinforcing a potential clinical and pathophysiological relevance of the SM dysregulation in OSCC. The inhibition of SM-activity might be a therapeutic avenue in OSCC, offering a clinically relevant opportunity to be explored.

New Insights for an Advanced Understanding of the Molecular Mechanisms in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC), the most common type of head and neck cancer, remains a highly challenging cancer to treat, largely due to the late diagnosis in advanced stages of the disease, which occurs in more than half of cases [...].

Jmjd2c maintains the ALDHbri+ cancer stemness with transcription factor SOX2 in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LSCC) is a deadly cancer in the world. Histone demethylase Jmjd2c is a key epigenetic regulator in various tumors, while the molecular mechanism underlying Jmjd2c regulatory in LSCC is still unclear. We used the aldehyde dehydrogenasebright (ALDHbri+) subtype as a research model for cancer stem cells (CSCs) in LSCC and detected the sphere formation ability and the proportion of ALDHbri+ CSCs with Jmjd2c interference and caffeic acid (CA) treatment. Additionally, we carried out bioinformatic analysis on the expression file of Jmjd2c RNAi mice and performed western blotting, qRT-PCR, Co-IP and GST pull-down assays to confirm the bioinformatic findings. Moreover, we generated Jmjd2c-silenced and Jmjd2c-SOX2-silenced ALDHbri+ tumor-bearing BALB/c nude mice to detect the effects on tumor progression. The results showed that Jmjd2c downregulation inhibited the sphere formation and the proportion of ALDHbri+ CSCs. The SOX2 decreased expression significantly in Jmjd2c RNAi mice, and they were positively co-expressed according to the bioinformatic analysis. In addition, SOX2 expression decreased in Jmjd2c shRNA ALDHbri+ CSCs, Jmjd2c and SOX2 proteins interacted with each other. Furthermore, Jmjd2c interference revealed significant blocking effect, and Jmjd2c-SOX2 interference contributed even stronger inhibition on ALDHbri+ tumor progression. The Jmjd2c and SOX2 levels were closely related to the development and prognosis of LSCC patients. This study indicated that Jmjd2c played key roles on maintaining ALDHbri+ CSC activity in LSCC by interacting with transcription factor SOX2. Jmjd2c might be a novel molecule for therapeutic targets and biomarkers in the diagnosis and clinical treatment of lung cancer.

Guanylate binding protein 5 is an immune-related biomarker of oral squamous cell carcinoma: A retrospective prognostic study with bioinformatic analysis.

BACKGROUND: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis. METHODS: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed. RESULTS: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival. CONCLUSIONS: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.