Subtype Of Squamous Cell Carcinoma Research Articles

Association Between Body Mass Index (BMI) and Occurrence of Esophageal Cancer

Aim: Esophageal cancer, one of the leading causes of cancer deaths globally, has been linked to body mass index (BMI). Studies have shown varying associations between BMI and different subtypes of esophageal cancer, namely adenocarcinoma and squamous cell carcinoma. However, there is limited literature from Pakistan on this topic. This study aims to investigate the association between BMI and the occurrence of esophageal cancer in a Pakistani population. Methods: A prospective observational study was conducted at the Oncology Department of Jinnah Postgraduate Medical Center, Pakistan. Participants included patients over 18 years old with suspected adenocarcinoma or squamous carcinoma of the esophagus. The study utilized a non-probability consecutive sampling technique, and data was collected using a predefined proforma. The association between BMI and types of esophageal carcinoma was analyzed using Chi-square tests. Results: The study found a statistically significant relationship between increasing BMI and the risk of developing esophageal adenocarcinoma. Conversely, a lower BMI was associated with a higher risk of squamous cell carcinoma. These findings align with existing literature that suggests different BMI associations with esophageal cancer subtypes. Conclusion: This study underscores the distinct relationships between BMI and different types of esophageal cancer. It highlights the importance of considering BMI as a factor in the risk assessment for esophageal cancer, particularly in the Pakistani population. Keywords: Esophageal Cancer, Body Mass Index (BMI), Adenocarcinoma, Squamous Cell Carcinoma

Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer

AbstractBackgroundNon‐small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5‐year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.MethodsThe UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain‐of‐function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.ResultsNR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.ConclusionsNR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

PPARγ Antagonists Exhibit Antitumor Effects by Regulating Ferroptosis and Disulfidptosis.

Oral squamous cell carcinoma (OSCC) stands as a prevalent subtype of head and neck squamous cell carcinoma, leading to disease recurrence and low survival rates. PPARγ, a ligand-dependent nuclear transcription factor, holds significance in tumor development. However, the role of PPARγ in the development of OSCC has not been fully elucidated. Through transcriptome sequencing analysis, we discovered a notable enrichment of ferroptosis-related molecules upon treatment with PPARγ antagonist. We subsequently confirmed the occurrence of ferroptosis through transmission electron microscopy, iron detection, etc. Notably, ferroptosis inhibitors could not completely rescue the cell death caused by PPARγ inhibitors, and the rescue effect was the greatest when disulfidptosis and ferroptosis inhibitors coexisted. We confirmed that the disulfidptosis phenotype indeed existed. Mechanistically, through qPCR and Western blotting, we observed that the inhibition of PPARγ resulted in the upregulation of heme oxygenase 1 (HMOX1), thereby promoting ferroptosis, while solute carrier family 7 member 11 (SLC7A11) was also upregulated to promote disulfidptosis in OSCC. Finally, a flow cytometry analysis of flight and multiplex immunohistochemical staining was used to characterize the immune status of PPARγ antagonist-treated OSCC tissues in a mouse tongue orthotopic transplantation tumor model, and the results showed that the inhibition of PPARγ led to ferroptosis and disulfidptosis, promoted the aggregation of cDCs and CD8+ T cells, and inhibited the progression of OSCC. Overall, our findings reveal that PPARγ plays a key role in regulating cell death in OSCC and that targeting PPARγ may be a potential therapeutic approach for OSCC.

First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes.

Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation. Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients. Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group. Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.

Identification of two distinct head and neck squamous cell carcinoma subtypes based on fatty acid metabolism-related signatures: Implications for immunotherapy and chemotherapy.

The dysregulation of lipid metabolism is a critical factor in the initiation and progression of tumors. In this investigation, we aim to characterize the molecular subtypes of head and neck squamous cell carcinoma (HNSCC) based on their association with fatty acid metabolism and develop a prognostic risk model. The transcriptomic and clinical data about HNSCC were obtained from public databases. Clustering analysis was conducted on fatty acid metabolism genes (FAMG) associated with prognosis, utilizing the non-negative matrix factorization algorithm. The immune infiltration, response to immune therapy, and drug sensitivity between molecular subtypes were evaluated. Differential expression genes were identified between subtypes, and a prognostic model was constructed using Cox regression analyses. A nomogram for HNSCC was constructed and evaluated. Thirty FAMGs have been found to exhibit differential expression in HNSCC, out of which three are associated with HNSCC prognosis. By performing clustering analysis on these 3 genes, 2 distinct molecular subtypes of HNSCC were identified that exhibit significant heterogeneity in prognosis, immune landscape, and treatment response. Using a set of 7778 genes that displayed differential expression between the 2 molecular subtypes, a prognostic risk model for HNSCC was constructed comprising 11 genes. This model has the ability to stratify HNSCC patients into high-risk and low-risk groups, which exhibit significant differences in prognosis, immune infiltration, and immune therapy response. Moreover, our data suggest that this risk model is negatively correlated with B cells and most T cells, but positively correlated with macrophages, mast cells, and dendritic cells. Ultimately, we constructed a nomogram incorporating both the risk signature and radiotherapy, which has demonstrated exceptional performance in predicting prognosis for HNSCC patients. A molecular classification system and prognostic risk models were developed for HNSCC based on FAMGs. This study revealed the potential involvement of FAMGs in modulating tumor immune microenvironment and response to treatment.

Landscape of esophageal cancer in Northern Kenya: experience from Garissa Regional Cancer Center.

Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. More than 80% of cases and deaths from EC occur within developing countries. In Kenya, cancer is the second leading cause of non-communicable disease deaths, and the trend of cancer deaths is projected to increase as per the 2020 GLOBOCAN report showing 42,116 new cases annually with a mortality of 27,092 cases. EC is the leading cancer in men and the third most common in women in Kenya. The Garissa Regional Cancer Center (GRCC) is one of the three regional cancer centres in Kenya. Despite the rising EC incidence in the region, there is limited data about the clinicopathological features and treatment outcomes of EC, therefore, this is the first study to look at the landscape of EC in the northern Kenya region. This was a retrospective study involving patients' file review of confirmed EC cases diagnosed or treated at the GRCC from 2019 to 2023. Data collected from each patient's chart included age, sex, risk factors, family history of EC, histological type, stage at diagnosis, treatment type and survival outcomes. For patients who were no longer in contact with the staff through clinic visits, the patients or their next of kin were contacted through phone calls for patients' survival status. Data were collected and stored using the STATA software. Over the study period, 124 esophageal cases were identified, 64 (51.4%) were males and 60 (48.4%) were females with a mean age of 57.56 years. In terms of risk factors, hot beverage consumption was the highest (47 cases, 37.9%), followed by history of peptic ulcer disease (27 cases, 21.8%), smoking (8.9%) and gastresophageal reflux disease (2 cases, 1.6%). Stage of diagnosis at presentation was stage 1 (1 case, 0.8%), stage 2 (22 cases, 17.8%), stage 3 (25 cases, 20.2%), stage 4 (50 cases, 40.3%), not staged (26 cases, 21%). The majority had squamous cell carcinoma (SCC) (105 cases, 84.7%), followed by adenocarcinoma (5 cases, 4%), anaplastic (5 cases, 4%), SCC+ adenocarcinoma (1 case, 0.8%), unknown histology (8 cases, 3.2%). Nearly all patients had triple assessment (Endoscopy, histology and staging scans) accounting for 92 cases (74.2%), 24 cases (20%) had endoscopy+ histology only, and 8 cases (3.2%) had only imaging scans. In terms of family history of EC, 20 cases (16.1%) had a family history of EC.Most of the patients were of ethnic Kenyan-Somali background (108 cases, Kenyan Somali, 87.1%) and majority were from Garissa County 96 cases (77.4%), 12 cases (9.7%) Wajir County, 12 cases (9.7%) from Tana River County and 4 cases (3.2%) from other counties. Many patients lacked health insurance (27 cases, 25.8%), while the majority paid out of pocket (92 cases,74.1%). Only 21% (26 cases) received chemotherapy alone, 5 cases (4%) got radiotherapy alone, 12.9% (16 cases) got chemoradiotherapy and a significant number of patients (77 cases, 62.1%) did not receive hospital-based cancer treatment. This study is the first esophageal study at the GRCC and in northern Kenya in general. Our study confirmed the clinicopathological features of one of the most common cancers in Kenya and more so among Kenyan-Somalis.The study also validates the predominance of histological subtypes of esophageal SCC with the late presentation, short survival and significant loss of follow-up. We recommend future EC studies employing a large prospective design with a large sample size to determine the impact of the new GRCC on the outcomes of EC patients and the local community.

Pregnancy complicated by small cell neuroendocrine carcinoma of the cervix

Small cell neuroendocrine carcinoma of the cervix (SCNCC) is considered to be an extremely rare, highly invasive and aggressive subtype of squamous cell carcinoma. It is particulary rare during pregnancy. Here we report a case in which a 32-year-old patient who was admitted to our Department at 27 completed weeks of gestation with intermittent vaginal spotting and a large amount of malodorous vaginal discharge. Gynecological examination revealed a 2 cm exophytic polypoid tumor coming out of the cervix. On rectal examination there was no clinically evident parametrial invasion. Biopsy of the cervix was performed and the diagnosis of small cell neuroendocrine carcinoma was established. We reviewed and discussed the features, diagnosis, treatment and prognosis of SCNCC diagnosed during pregnancy.

Abstract LB288: Reducing the effect of cellular stress in murine oral tumors with pharmacological blockade of β-catenin/CBP activity

Abstract Oral squamous cell carcinoma (OSCC), a primary subtype of head and neck squamous cell carcinoma (HNSCC), is a complex malignancy comprising multiple anatomical sites. OSCC ranks among the deadliest cancers globally, with a 5-year survival rate of ~65%. In previous studies, we have shown that pharmacological blockade of Wnt/β-catenin/CBP activity with small molecule inhibitors effectively abolished oncogenic cell phenotypes in OSCC. However, the underlying mechanisms promoting changes in OSCC cell identities remain unknown. To address this knowledge gap, we used an immunocompetent mouse model of OSCC induced by a tobacco-derived carcinogen, 4-nitroquinoline-1-oxide (4NQO), to interrogate cell states by single-cell RNA sequencing (scRNAseq) of tongue tissues from healthy mice (n=2), 4NQO-derived mouse tongue OSCC (n=2), and from 4NQO-derived mouse tongue tissues treated with an inhibitor of β-catenin/CBP (n=4), and generated a high-quality dataset comprising ~50K cells across all conditions. We performed multiple analyses of the generated data to catalogue the cell type repertoire and its changes among conditions. We observed significant changes in cellular composition between the 4NQO-induced and inhibitor-treated groups. The proportion of epithelial cells decreased upon treatment consistent with greatly diminished tumor volumes, while endothelial and fibroblast populations increased compared to the 4NQO control group. Epithelial sub-typing using known markers revealed a decrease in basal cancer stem-like cells (Krt5+, Krt14+) concomitant with an increase in cycling cells (Top2a+, Cdc20+). In addition, we identified a decrease in a stress cell phenotype associated with the AP-1 complex (Jun+, Fos+). The latter subgroup exhibited a positive enrichment for the “stress” module (n=100 genes) derived from human HNSCC patients described by Puram et al. To further validate the relationship between the stress subtype with β-catenin/CBP activity and its relation to the AP-1 complex, we projected the Puram stress module and the down-regulated signature from the β-catenin/CBP inhibitor-treated group compared with the 4NQO-control group onto independent cohorts of human subjects with HPV-negative HNSCC. We used both the bulk TCGA RNA-seq subset (n=367 patients) and a previously published scRNAseq dataset from Choi et al., specifically profiling the epithelial compartment (3K cells, n = 16 patients). We observed highly significant positive association of the stress program and β-catenin/CBP activity in both datasets (pearson ρ = 0.74 and 0.70, respectively), indicating that inhibition of β-catenin/CBP activity reduces the stress response. Our results suggest that mitigation of tumorigenic profiles in 4NQO-induced tumors upon inhibition of β-catenin/CBP signaling in OSCC may serve as an effective treatment strategy for the benefit of human patients and shed further light into the molecular mechanisms driving treatment response. Citation Format: Mohammed Muzamil Khan, Eric Reed, Lina Kroehling, Kenichi Nomoto, Junji Matsui, Manish Bais, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti. Reducing the effect of cellular stress in murine oral tumors with pharmacological blockade of β-catenin/CBP activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB288.

EHMT2 Suppresses ARRB1 Transcription and Activates the Hedgehog Signaling to Promote Malignant Phenotype and Stem Cell Property in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) represents the primary subtype of head and neck squamous cell carcinoma (HNSCC), characterized by a high morbidity and mortality rate. Although previous studies have established specific correlations between euchromatic histone lysine methyltransferase 2 (EHMT2), a histone lysine methyltransferase, and the malignant phenotype of OSCC cells, its biological functions in OSCC remain largely unknown. This study, grounded in bioinformatics predictions, aims to clarify the influence of EHMT2 on the malignant behavior of OSCC cells and delve into the underlying mechanisms. EHMT2 exhibited high expression in OSCC tissues and demonstrated an association with poor patient outcomes. Artificial EHMT2 silencing in OSCC cells, achieved through lentiviral vector infection, significantly inhibited colony formation, migration, invasion, and cell survival. Regarding the mechanism, EHMT2 was found to bind the promoter of arrestin beta 1 (ARRB1), thereby suppressing its transcription through H3K9me2 modification. ARRB1, in turn, was identified as a negative regulator of the Hedgehog pathway, leading to a reduction in the proteins GLI1 and PTCH1. Cancer stem cells (CSCs) were enriched through repeated sphere formation assays in two OSCC cell lines. EHMT2 was found to activate the Hedgehog pathway, thus promoting sphere formation, migration and invasion, survival, and tumorigenic activity of the OSCC-CSCs. Notably, these effects were counteracted by the additional overexpression of ARRB1. In conclusion, this study provides novel evidence suggesting that EHMT2 plays specific roles in enhancing stem cell properties in OSCC by modulating the ARRB1-Hedgehog signaling cascade.

Abstract 3499: Non-small cell lung cancer (NSCLC) histology classification using DNA methylation data captured from liquid biopsies

Abstract Background: Non-small cell lung cancer (NSCLC) makes up ~85% of lung cancers, and its major subtypes are adenocarcinoma (AD) and squamous cell carcinoma (SC). The histology classification of NSCLC has significant therapeutic and prognostic implications. As liquid biopsies are rapid and non-invasive, computational methods to classify NSCLC subtypes using cell-free DNA (cfDNA) are desired. Methods: Using The Cancer Genome Atlas (TCGA) NSCLC methylation data, we developed a method to classify AD and SC subtypes from cfDNA samples. We mapped TCGA methylation data to Guardant Infinity’s promoter regions and transformed them to allow for the transfer of the TCGA trained model to Infinity cfDNA epigenomic data. An advantage of this approach is that TCGA training data originates from the primary tumor, while cfDNA samples have low tumor fraction (TF) and may also contain signals from metastatic tumors. We trained a penalized Logistic Regression model with LASSO. To better fit the model to Infinity cfDNA data, we performed region filtering. Results: Our model effectively classified AD and SC subtypes from TCGA samples (AUC 0.97) (10-fold cross validation; Table 1). When evaluating on cfDNA samples with epigenomic TF ≥ 1%, the final model shows reasonable performance (AUC 0.94) (Table 1); the performance decreases when reduced to TF > 0.05% (AUC 0.89) as expected (Table 1). When evaluating cfDNA from uncategorized lung samples, the predicted AD probabilities have significant association with KRAS mutations (p-value = 0.027). Conclusion: Our results show that the penalized Logistic Regression model trained with tissue TCGA methylation data through mapping, transformation, and region selection can classify NSCLC subtypes from cfDNA samples. This method may offer a fast, non-invasive tool to inform subtype-based clinical decisions, especially in the setting of poorly-differentiated carcinomas, and to identify subtype switches upon resistance to targeted therapies. Table 1: Model evaluation on tissue TCGA samples and cfDNA Infinity samples (different TF cutoffs) Sample type N samples AUC Accuracy Sensitivity Specificity Precision F1 score tissue TCGA 907 0.97 0.93 0.94 +/- 0.02 0.93 +/- 0.02 0.94 +/- 0.02 0.94 +/- 0.01 cfDNA Infinity 17 (TF ≥ 1%) 0.94 0.88 0.83 +/- 0.3 0.91 +/- 0.17 0.83 +/- 0.3 0.83 +/- 0.21 cfDNA Infinity 29 (TF > 0.05%) 0.89 0.83 0.88 +/- 0.23 0.81 +/- 0.17 0.64 +/- 0.28 0.74 +/- 0.2 Citation Format: Laura Tung, Denis Tolkunov, Catalin Barbacioru, Deepika Kale, Scott Shell, Jill Tsai, Leylah Drusbosky, Kaushal Parikh, Han-Yu Chuang. Non-small cell lung cancer (NSCLC) histology classification using DNA methylation data captured from liquid biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3499.

Prognostic significance of T lymphocyte subgroups (CD4 and CD8) in lung cancer patients after neoadjuvant chemotherapy

ObjectiveThe basis for current and future lung cancer immunotherapy depends on our knowledge of molecular mechanisms of interactions between tumor and immune system cells. Interactions that occur between different intratumoral populations of the same cells are important. In our study, we aimed to evaluate relationship between the clinical and prognostic features and T lymphocyte subgroups of patients with lung tumors after neoadjuvant treatment.MethodsA total of 72 patients were included in our study, including study group, 39 of whom received neoadjuvant chemotherapy. Clinical/radiological/pathological findings of patients and CD4/CD8 staining rates in peritumoral/intratumoral areas were recorded.ResultsOur study revealed significantly lower intratumoral CD4 + T cell density and lower intratumoral CD4/CD8 ratio in primary tumor after neoadjuvant therapy (respectively, 0.012 and 0.016). Considering tumor types, when control-study groups were compared, inflammation was statistically significant only in adenocarcinoma subtype; intratumoral CD4/CD8 ratio was statistically significant only in squamous-cell carcinoma subtype (respectively, p = 0.0008 and p = 0.0139). When CD4 + T lymphocytes and CD8 + T lymphocytes and CD4/CD8 ratio were compared between control and study groups in low-stage patients according to clinical stages, only intratumoral CD4 + T lymphocyte values and intratumoral CD4/CD8 ratio were significant (respectively, p = 0.0291 ve p = 0.0154).ConclusionAll cell types of innate and adaptive intratumoral immunity can affect lung cancer tissues simultaneously, and these interactions have a very complex structure. Understanding the tumor microenvironment and the different roles of associated cancer immune cells may lead to the discovery of new targets for immunological therapies and increased survival times in lung cancer.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

Causality Assessment Between Idiopathic Inflammatory Myopathies and Lung Cancer: A Bidirectional 2-Sample Mendelian Randomization.

Although observational studies have revealed associations between idiopathic inflammatory myopathies (IIMs) and lung cancer (LC), they have not established a causal relationship between these 2 conditions. We used a 2-sample Mendelian randomization approach to examine the bidirectional causal associations between IIMs and LC, using single-nucleotide polymorphisms selected from high-quality genome-wide association studies in the FinnGen database. Sensitivity analyses were conducted to assess potential heterogeneity and pleiotropy impacts on the Mendelian randomization results. Our analysis demonstrated a positive causal effect of genetically increased IIM risk on LC (odds ratio, 1.114; 95% confidence interval, 1.057-1.173; p = 5.63 × 10-5), particularly on the lung squamous cell carcinoma subtype (odds ratio, 1.168, 95% confidence interval, 1.049-1.300, p = 0.00451), but not on lung adenocarcinoma or small cell lung cancer. No causal effect of LC on IIMs was identified. Sensitivity analyses indicated that horizontal pleiotropy was unlikely to influence causality, and leave-one-out analysis confirmed that the observed associations were not driven by a single-nucleotide polymorphism. Our findings offer compelling evidence of a positive causal relationship between IIMs and LC, particularly with regard to lung squamous cell carcinoma, in the European population. Conversely, there is no evidence of LC causing IIMs. We recommend that LC diagnosis consider the specific characteristics of IIMs.

Identifying intense inflammatory subtype of esophageal squamous cell carcinoma using clustering approach.

To establish a risk-stratification system for predicting the postoperative recurrence of esophageal squamous cell carcinoma, this study aimed to evaluate the prognostic value of clusters based on blood inflammation and coagulation markers and investigate their correlation with serum cytokines and genetic alteration. This single-center, retrospective cohort study enrolled 491 patients with esophageal cancer who underwent subtotal esophagectomy between 2004 and 2012. For cluster exploration, nonhierarchical cluster analysis and k-means were applied using serum C-reactive protein, albumin, fibrinogen, and platelet-lymphocyte ratio as variables. Then, multivariate survival analysis was conducted to investigate the association of clusters with recurrence-free survival. To characterize the clusters, serum interleukin-6, interleukin-8, and genetic alteration in primary tumors, the PleSSision-Rapid panel, which can evaluate 160 representative driver genes, was used. Patients were classified into clusters 1, 2, and 3, which included 24 (5%), 161 (33%), and 306 (62%) patients, respectively. Compared with cluster 3, cluster 1 or 2 had significantly worse recurrence-free survival. Based on the multivariable analysis using cluster, pStage, and age as covariates, cluster was an independent prognostic factor for recurrence-free survival (hazard ratio, 1.55; 95% confidence interval, 1.08-2.21; P = 0.02). The percentage of serum interleukin-6 and interleukin-8 levels was the highest in cluster 1, followed by clusters 2 and 3. In 23 patients with available genomic profiles, no significant difference in representative genomic alterations was observed. Non-biased clustering using inflammation and coagulation markers identified the intense inflammatory subtype, which had an independent prognostic effect on recurrence-free survival.

Mononuclear phagocyte system-related multi-omics features yield head and neck squamous cell carcinoma subtypes with distinct overall survival, drug, and immunotherapy responses

BackgroundRecent research reported that mononuclear phagocyte system (MPS) can contribute to immune defense but the classification of head and neck squamous cell carcinoma (HNSCC) patients based on MPS-related multi-omics features using machine learning lacked.MethodsIn this study, we obtain marker genes for MPS through differential analysis at the single-cell level and utilize “similarity network fusion” and “MoCluster” algorithms to cluster patients’ multi-omics features. Subsequently, based on the corresponding clinical information, we investigate the prognosis, drugs, immunotherapy, and biological differences between the subtypes. A total of 848 patients have been included in this study, and the results obtained from the training set can be verified by two independent validation sets using “the nearest template prediction”.ResultsWe identified two subtypes of HNSCC based on MPS-related multi-omics features, with CS2 exhibiting better predictive prognosis and drug response. CS2 represented better xenobiotic metabolism and higher levels of T and B cell infiltration, while the biological functions of CS1 were mainly enriched in coagulation function, extracellular matrix, and the JAK-STAT signaling pathway. Furthermore, we established a novel and stable classifier called “getMPsub” to classify HNSCC patients, demonstrating good consistency in the same training set. External validation sets classified by “getMPsub” also illustrated similar differences between the two subtypes.ConclusionsOur study identified two HNSCC subtypes by machine learning and explored their biological difference. Notably, we constructed a robust classifier that presented an excellent classifying prediction, providing new insight into the precision medicine of HNSCC.

Aberrated PSMA1 expression associated with clinicopathological features and prognosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a globally prevalent cancer with significant mortality rates. OSCC a predominant subtype of head and neck squamous cell carcinoma (HNSCC), poses a substantial health burden. Despite advancements in diagnosis and therapy, OSCC prognosis remains poor. The 26S proteasome, a cellular protein degradation complex, is associated with cancer, including PSMA1, a proteasomal subunit, which is upregulated in various cancers. We analyzed PSMA1 expression using TCGA data, validated it in OSCC samples using real-time PCR, and explored its role through various databases. Tumor and adjacent normal tissues from OSCC patients were examined, and PSMA1 expression was analyzed. Survival analysis assessed the impact of PSMA1 on patient outcomes, while immune infiltration was examined using the TIMER database. GeneMANIA, STRING, and Metascape were utilized for gene interaction and pathway analysis. PSMA1 was significantly upregulated in OSCC and HNSCC. Its overexpression correlated with advanced clinicopathological features and poorer prognosis in HNSCC patients. PSMA1 expression is also related to immune cell infiltration. Gene interaction analysis revealed PSMA1 involvement in proteolysis regulation, suggesting its potential as a therapeutic target. PSMA1 upregulation in HNSCC association with adverse clinicopathological features and prognosis underscores its potential significance. Further research is warranted to elucidate its molecular mechanisms and therapeutic potential in OSCC management.

A Case Report of 4-Years Old Patient With Nuclear Protein in Testis Midline Carcinoma of Larynx

Nuclear protein in testis midline carcinoma (NMC) is an extremely aggressive subtype of squamous cell carcinoma characterized by chromosomal rearrangements of the nuclear protein in testis (NUT) gene. NMC predominantly arises in the anatomical midline locations of the body, with a high occurrence in the thoracic, head and neck regions. However, NMC remains a rarely reported disease, making its inclusion in the initial differential diagnosis challenging. This case involves a 4-year-old boy who presented with a neck mass initially diagnosed as a poorly differentiated carcinoma originating from the larynx with the cervical Lymph node metastasis. However, further tests confirmed the diagnosis of NUT midline carcinoma. This case highlights the importance of conducting NUT immunohistochemistry in cases of squamous cell carcinoma and undifferentiated carcinoma occurring in the head and neck, as it can provide meaningful insights for diagnosis and treatment decisions.

Peranan Sekuen Diffusion Weighted Imaging (DWI) Pada Pemeriksaan MRI Soft Tissue Leher Kasus Kanker Nasofaring (Studi Literatur)

The aim of this research is to determine the role of the Diffusion Weighted Imaging (DWI) sequence in Soft Tissue MRI examinations of the neck in cases of nasopharyngeal cancer and to determine the advantages of using the Diffusion Weighted Imaging (DWI) sequence in MRI Soft Tissue examinations of the neck in cases of nasopharyngeal cancer. The research method used was a descriptive qualitative research method with a literature study method. The results of the literature review research showed: 1) Nasopharyngeal cancer, especially squamous cell carcinoma, can be treated with radiation therapy where treatment failure is still a serious problem, especially in advanced cases. DWI and ADC are imaging methods that utilize the movement of water inside. DWI provides additional information regarding response to treatment in hard-to-reach cases of nasopharyngeal cancer. plays an important role in detection, evaluation of response to treatment, and early monitoring of chemoradiotherapy therapy. DWI also provides information that helps distinguish between tissue experiencing post-RTH fibrosis and areas that may contain active cancer cells. DWI and ADC are also useful in tumor staging, delineation of target volumes, and detection of tumor recurrence. Elevated ADC may be indicative of a favorable response to therapy, whereas low pretreatment ADC values ​​may predict a favorable response. In the diagnosis of nasopharyngeal cancer, DWI and ADC also help differentiate squamous cell carcinoma subtypes, predict response to chemoradiation therapy, and determine the appropriate time for alternative treatment regimens. 2) DWI and ADC provide advantages in the diagnosis and monitoring of nasopharyngeal cancer. DWI can image restrictions on water diffusion within tissue, helping to detect areas of high cell density associated with tumors. Its advantages include sensitivity to microenvironmental changes and the ability to early identify recurrence or secondary cancer post-radiation therapy.

Mass cytometry and transcriptomic profiling reveal PD1 blockade induced alterations in oral carcinogenesis.

Oral squamous cell carcinoma is the predominant subtype of head and neck squamous cell carcinoma, characterized by a challenging prognosis. In this study, we established a murine model of oral carcinogenesis using 4-nitroquinoline-1-oxide (4-NQO) induction to investigate the impact of immunotherapy on microenvironmental alterations. Mice in the precancerous condition were randomly divided into two groups:one receiving programmed death-1 (PD1) monoclonal antibody treatment and the other, control immunoglobulin G. Our observations showed that while PD1 blockade effectively delayed the progression of carcinogenesis, it did not completely impede or reverse it. To unravel the underlying reasons for the limited effectiveness of PD1 blockade, we collected tongue lesions and applied mass cytometry (CyTOF) and RNA sequencing (RNA-seq) to characterize the microenvironment. CyTOF analysis revealed an increased macrophage subset (expressing high levels of IFNγ and iNOS) alongside a diminished Th1-like subset (exhibiting low expression of TCF7) and three myeloid-derived suppressor cell subsets (displaying low expression of MHC Class II or IFNγ) following anti-PD1 treatment. Notably, we observed an increased presence of cancer-associated fibroblasts (CAFs) expressing collagen-related genes after PD1 blockade. Furthermore, we found a negative correlation between the infiltration levels of CAFs and CD8+ T cells. These findings were validated in murine tongue tissue slides, and publicly available multi-omics datasets. Our results suggest that CAFs may impair the therapeutic efficacy of PD1 blockade in oral carcinogenesis by the remodeling of the extracellular matrix.

Papillary Variant of Oral Squamous Cell Carcinoma of Alveolar Mucosa- A Case Report and Review

Papillary Squamous Cell Carcinoma (PSCC) is a less frequent subtype of Squamous Cell Carcinoma (SCC) with a more favorable prognosis compared to conventional oral squamous cell carcinoma. PSCC has a distinctive exophytic and papillary projection. The upper aerodigestive tract is the most commonly affected site with a higher incidence of occurrence in the larynx. The papillary variant of oral squamous cell carcinoma involving gingiva or alveolar ridge is relatively uncommon and less reported. Other differential diagnosis of papillary gingival masses is reactive gingival lesions and fungal infections. An accurate diagnosis is vital for both therapeutic and prognostic purposes. This article describes the case of papillary variant oral squamous cell carcinoma in a 75-year-old male in the maxillary alveolar region depicting histopathological features of exophytic growth with hyperplastic stratified squamous epithelium with basaloid cells invading the underlying connective tissue.