Squamous Cell Carcinoma Group Research Articles

Transcriptomic analysis of genes associated with vitamin D receptor signalling reveals differences between skin cancers.

Vitamin D activates the vitamin D receptor (VDR), which dimerizes preferentially with the retinoid X receptor-α (RXRα). This heterodimer connects with genetic elements responsive to vitamin D, inhibiting or stimulating gene activity. We performed Nanostring® analysis of VDR/RXRα to compare the mRNA expression of this heterodimer and their correlated transcriptomes in non-melanoma skin cancer (basal cell carcinomas (BCC) and squamous cell carcinomas (SCC)) and melanocytic lesions (intradermal nevi (IN), and melanomas (MM)) with control skin. To evaluate VDR, RXRα and other 22 correlated genes in BCC, SCC, IN and MM, paraffin samples had their transcriptomes analysed using Nanostring®, a platform that allows multiple mRNA analyses. There were 46 samples, including 11 BCC, 10 SCC, 10 IN, 12 MM and 3 pools of control skins. Most mRNAs differed between the lesion groups and the control group. BCC and SCC NCOR2 were upregulated; in MM and IN, RXRγ was higher than in the control group. TP53, FOXO3 and MED1 showed a significant difference when we compared the BCC group to the SCC group. Melanoma and intradermal nevi differed only in AhR. VDR and RXRα were lower than the control in all groups. The panel shows a clear difference between the non-melanocytic cancers and, on the other hand, a slight difference between the melanocytic lesions. The study of vitamin D's influence through its receptor and RXRα is an exciting issue for understanding the importance of this pathway, and the present study can impact the prevention and treatment strategies, mainly in non-melanocytic tumours.

The impact of histological subtype on postoperative recurrence pattern and timing in locally advanced esophagogastric junction cancer

PurposeThe differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes.MethodsA retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared.ResultsAfter a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence.ConclusionsThe pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods.

Perioperative Predictive Factors for Tumor Regression and Survival in Non-Small Cell Lung Cancer Patients Undergoing Neoadjuvant Treatment and Lung Resection.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into a lung adenocarcinoma group (LUAD) and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small-cell lung cancer were included in the study. A total of 58 (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Additionally, 9 (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III, respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7 cm), and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR [95% confidence interval, p-value] of 6.88 [2.40-19.77, p < 0.0001], 3.13 [1.11-8.83, p = 0.0310], and 3.76 [1.20-11.81, p = 0.0233], respectively). Age > 70 years, extended resection > one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Prognostic significance of neutrophil to lymphocyte ratio (NLR) in oral squamous cell carcinoma

BackgroundTumor microenvironment is one of the evading research in the progression of cancers. Circulating neutrophils reflect the system's inflammatory response and study the growth of tumor cells thereby inducing cancer progression. Aim and objectivesThe current study aims to evaluate the NLR ratio in oral squamous cell carcinoma group and to compare it with that of normal control and Premalignant group. Material and methodsThis study is retrospective, the medical records of 48 OSCC patients, 48 Leukoplakia patients, and 48 normal healthy controls were taken. Association between NLR and clinicopathological variables were assessed. Tukey's post-hoc test was done to compare the variables. Kaplan Meier analysis was done for the analysis of overall survival. ResultsThe NLR ratio was assessed and compared between the three groups. The mean NLR ratio was found to be 3.79 in Oral squamous cell carcinoma patients, 2.62 in leukoplakia patients, and 2.07 in the normal control group. ConclusionAn increase in NLR levels was seen in OSCC patients. Increased NLR was also seen associated with advanced tumor staging and grading.

Evaluation of Triglyceride-Glucose Index Elevation as a Biomarker and Risk Factor in Laryngeal Squamous Cell Carcinoma.

Insulin resistance is associated with increased levels of IGF-1. IGF-1 has been shown to increase the risk of laryngeal squamous cell carcinoma. The Triglyceride-glucose index (TyG index) is a marker of insulin resistance. Our study aimed to investigate the relationship between the TyG index and laryngeal squamous cell carcinoma. Retrospective cohort study. Two tertiary care academic hospitals. The study included 53 patients with laryngeal squamous cell carcinoma (Group 1) and 48 healthy volunteers (Group 2). Laryngeal cancer patients were divided into two groups according to their stage. Stages I and II were named Group 1A, and Stages III and IV were called Group 1B. The TyG index was calculated as ln [fasting Triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. The effect of the TyG index on laryngeal cancer was investigated on the parameters of sex, age, body mass index, and stage of the disease. There were no significant differences in age, sex, and BMI between the groups. The TyG index of group 1 (4.75 ± 0.33) was significantly higher than that of group 2 (4.59 ± 0.15). The TyG index value of group 1B (4.84 ± 0.31) was significantly higher than both group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15). There was no significant difference between the TyG index values of group 1A (4.61 ± 0.32) and group 2 (4.59 ± 0.15). The TyG index may be a promising laryngeal squamous cell carcinoma biomarker. People with a higher TyG index may have a higher incidence of laryngeal squamous cell carcinoma and a higher risk of progression.

Diagnostic efficiency of intravoxel incoherent motion-based virtual magnetic resonance elastography in pulmonary neoplasms

BackgroundThe aim of the study were as below. (1) To investigate the feasibility of intravoxel incoherent motion (IVIM)-based virtual magnetic resonance elastography (vMRE) to provide quantitative estimates of tissue stiffness in pulmonary neoplasms. (2) To verify the diagnostic performance of shifted apparent diffusion coefficient (sADC) and reconstructed virtual stiffness values in distinguishing neoplasm nature.MethodsThis study enrolled 59 patients (37 males, 22 females) with one pulmonary neoplasm who underwent computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) with pathological diagnosis (26 adenocarcinoma, 10 squamous cell carcinoma, 3 small cell carcinoma, 4 tuberculosis and 16 non-specific benign; mean age, 60.81 ± 9.80 years). IVIM was performed on a 3 T magnetic resonance imaging scanner before biopsy. sADC and virtual shear stiffness maps reflecting lesion stiffness were reconstructed. sADC and virtual stiffness values of neoplasm were extracted, and the diagnostic performance of vMRE in distinguishing benign and malignant and detailed pathological type were explored.ResultsCompared to benign neoplasms, malignant ones had a significantly lower sADC and a higher virtual stiffness value (P < 0.001). Subsequent subtype analyses showed that the sADC values of adenocarcinoma and squamous cell carcinoma groups were significantly lower than non-specific benign group (P = 0.013 and 0.001, respectively). Additionally, virtual stiffness values of the adenocarcinoma and squamous cell carcinoma subtypes were significantly higher than non-specific benign group (P = 0.008 and 0.001, respectively). However, no significant correlation was found among other subtype groups.ConclusionsNon-invasive vMRE demonstrated diagnostic efficiency in differentiating the nature of pulmonary neoplasm. vMRE is promising as a new method for clinical diagnosis.

Cytomorphological Features as a Subtyping Tool of Non-Small-Cell Lung Cancer in Brushing Bronchoscopic Samples.

Nowadays, the separation of adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) is crucial given that there are new specific targeted therapies. So, the aim of this study was to examine the differences in cytomorphological features between ADC and SCC in bronchoscopic brush samples. The retrospective study was conducted over a 3-year period at Western Balkan University Hospital. All brushing samples were analysed. According to the histopathological report, patients were classified into ADC and SCC groups. The cytomorphological features analysed in 95 samples were presence of necrosis, cell distribution, nuclear atypia, size of nuclei, and visibility of nucleoli. Statistical analysis was performed in JASP, and P values <0.05 were considered significant. The necrotic background was more frequent in SCC samples. Small clusters sized ≤200 µm were found in 17.95% of samples from the SCC group and 53.57% in the ADC group. Large clusters sized >400 µm were found in 43.59% in the SCC group, while in the ADC group, it was found in 5.36%. There were no differences in nuclear atypia between groups. Nuclei that were >5x lymphocyte size were found more often in samples from ADC than in the SCC group (37.50 vs 10.25%). In 89.75% of samples from the SCC group, nuclei were ≤5x lymphocyte sizes, while in the ADC group, the percentage was 63.5%. Nucleoli were more often visible in samples from the ADC group compared to the SCC group (92.86% vs 64.10%, P < 0,05). Small clusters, large nuclei, and visible nucleoli were more frequent in the ADC group (P < 0.05), while large clusters, small nuclei, and invisible nucleoli were more frequent in the SCC group (P < 0.05).

Characteristics of the magnetic resonance imaging findings of cervical gastric-type adenocarcinoma

This study identified the distinct magnetic resonance imaging findings of cervical gastric-type adenocarcinoma (GAS) that can help differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA) and reveal the radiologic-pathologic correlation. All consecutive patients with cervical GAS treated at our hospital from November 2009 to August 2021 were included. The SCC and UEA cases were considered controls. Tumor location, tumor shape, presence and size of cysts, presence of uterine fluid, and apparent diffusion coefficient (ADC) were evaluated. Overall, 18 GAS, 55 SCC, and 23 UEA cases were evaluated. The tumor was located in the entire cervix in 13/18 GAS cases, whereas it was predominantly located in the lower cervix in 38/55 SCC cases and 14/23 UEA cases. Most GAS cases exhibited a diffuse infiltration growth pattern (17/18), whereas most SCC and UEA cases exhibited a mass-forming pattern (39/55 and 20/23, respectively). Moreover, the percentages of cases presenting microcysts or macrocysts and undergoing uterine fluid collection were significantly higher in the GAS group (14/18 and 13/18) than in the SCC and UEA groups. ADC was significantly higher in the GAS group than in the SCC group (1.092×10-3 vs. 0.819×10-3 mm2/s). This study revealed that GAS is characterized by tumor presence in the entire cervix, infiltrative growth pattern, intrauterine fluid collection, and frequent microcyst or macrocyst formation. Moreover, ADC was significantly higher in the GAS group than in the SCC group.

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.

Composition of the sputum bacterial microbiome of patients with different pathomorphological forms of non-small-cell lung cancer.

Recent studies have shown that the bacterial microbiome of the respiratory tract influences the development of lung cancer. Changes in the composition of the microbiome are observed in patients with chronic inflammatory processes. Such microbiome changes may include the occurrence of bacteria that cause oxidative stress and that are capable of causing genome damage in the cells of the host organism directly and indirectly. To date, the composition of the respiratory microbiome in patients with various histological variants of lung cancer has not been studied. In the present study, we determined the taxonomic composition of the sputum microbiome of 52 patients with squamous cell carcinoma of the lung, 52 patients with lung adenocarcinoma and 52 healthy control donors, using next-generation sequencing (NGS) on the V3-V4 region of the bacterial gene encoding 16S rRNA. The sputum microbiomes of patients with different histological types of lung cancer and controls did not show significant differences in terms of the species richness index (Shannon); however, the patients differed from the controls in terms of evenness index (Pielou). The structures of bacterial communities (beta diversity) in the adenocarcinoma and squamous cell carcinoma groups were also similar; however, when analyzed according to the matrix constructed by the Bray-Curtis method, there were differences between patients with squamous cell carcinoma and healthy subjects, but not between those with adenocarcinoma and controls. Using the LEFse method it was possible to identify an increase in the content of Bacillota (Streptococcus and Bacillus) and Actinomycetota (Rothia) in the sputum of patients with squamous cell carcinoma when compared with samples from patients with adenocarcinoma. There were no differences in the content of bacteria between the samples of patients with adenocarcinoma and the control ones. The content of representatives of the genera Streptococcus, Bacillus, Peptostreptococcus (phylum Bacillota), Prevotella, Macellibacteroides (phylum Bacteroidota), Rothia (phylum Actinomycetota) and Actinobacillus (phylum Pseudomonadota) was increased in the microbiome of sputum samples from patients with squamous cell carcinoma, compared with the control. Thus, the sputum bacterial microbiome of patients with different histological types of non-small-cell lung cancer has significant differences. Further research should be devoted to the search for microbiome biomarkers of lung cancer at the level of bacterial species using whole-genome sequencing.

Outcomes of thyroidectomy for secondary thyroid malignancies, a single center experience

BackgroundMetastasis of primary malignancies of other organs to the thyroid gland is a rare condition that may pose a diagnostic challenge. In this study, we aimed to report the clinicopathologic features and outcomes of patients treated for secondary thyroid malignancies in our center.Materials and methodsThe results of patients who underwent thyroidectomy in our clinic between 2015 and 2023 were evaluated retrospectively. Four patients who met the inclusion criteria were evaluated.ResultsThe primary tumor was renal cell carcinoma in 2 patients and squamous cell carcinoma of the lung in 2 patients. Median age was 64 years (min:59–max:69). The median nodule diameter was 2.85 cm. Extrathyroidal spread was present in 1 patient with renal cell carcinoma metastasis. The other patient with renal cell carcinoma metastasis had lymphatic invasion. Vascular invasion was detected in 1 patient with renal cell carcinoma metastasis and 1 patient with squamous cell carcinoma of the lung metastasis. Surgical margin positivity was present in 1 patient in each group. The median overall survival time was 27 (min:10–max:44) months in the renal cell carcinoma group and 11 (min:6–max:16) months in the squamous cell carcinoma group. After the diagnosis of primary renal cell carcinoma, one patient metastasized to thyroid tissue 43.00 and one patient 94.00 months later. In the squamous cell carcinoma group, one patient showed metastasis to thyroid tissue 6.00 months after the primary diagnosis, while the other patient was first diagnosed with metastatic tissue.ConclusionsMetastasis to the thyroid gland is a rare phenomenon with an incidence of 0.22% in all thyroid malignancies. It may occur before the detection of the primary tumor or during the follow-up of the primary malignancy. Although the overall prognosis is poor, it can be treated surgically.

Evaluation of salivary tumor necrosis factor α as a diagnostic biomarker in oral submucosal fibrosis and squamous cell carcinoma of the oral cavity and oropharynx: a cross sectional observational study.

Tumor necrosis factor α (TNF-α) is known to be associated with chronic inflammation, and its expression has been shown to increase in advanced cancers. Chronic inflammation is a characteristic feature of oral submucous fibrosis (OSMF), which is a potentially malignant disorder (PMD). Squamous cell carcinoma (SCC) is associated with considerable mortality and morbidity and an early detection or monitoring would greatly help in achieving an effective cure. TNF-α was thus evaluated for use as a biomarker in the present study according to the stage of OSMF and histological grade of SCC in the oral cavity and oropharynx. This study included 45 patients divided into 3 groups-OSMF group, SCC group and control group-each comprising 15 participants. Saliva samples were collected from each patient, and salivary TNF-α levels were estimated using an ELISA kit. Statistical analysis revealed no significant differences in TNF-α levels among the OSMF, SCC and control groups; however, there was an increase in the salivary TNF-α level in patients with stage 3 disease according to the clinical stage of OSMF, for which the p value was 0.027. An increase in the TNF-α concentration with increasing clinical stage suggested a role for TNF-α in the spread of OSMF involvement in anatomical structures of the oral cavity and oropharynx. No significant difference in salivary TNF-α levels was noted among the OSMF, SCC and control groups. The study showed a positive correlation of TNF-α with increasing stages of OSMF but was not a reliable biomarker in the categorization of the same.

3D MR elastography-based stiffness as a marker for predicting tumor grade and subtype in cervical cancer

BackgroundIncreasing evidence has indicated that high tissue stiffness (TS) may be a potential biomarker for evaluation of tumor aggressiveness. PurposeTo investigate the value of magnetic resonance elastography (MRE)-based quantitative parameters preoperatively predicting the tumor grade and subtype of cervical cancer (CC). Study typeRetrospective. PopulationTwenty-five histopathology-proven CC patients and 7 healthy participants. Field strength/sequence3.0T, magnetic resonance imaging (MRI) (LAVA-flex) and MRE with a three-dimensional spin-echo echo-planar imaging. AssessmentThe regions of interest (ROIs) were manually drawn by two observers in tumors to measure mean TS, storage modulus (G′), loss modulus (G″) and damping ratio (DR) values. Surgical specimens were evaluated for tumor grades and subtypes. Statistical testsIntraclass correlation coefficient (ICC) was expressed in terms of inter-observer agreements. t-test or Mann-Whitney nonparametric test was used to compare the complex modulus and apparent diffusion coefficient (ADC) values between different tumor groups. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic performance. ResultsThe TS of endocervical adenocarcinoma (ECA) group was significantly higher than that in squamous cell carcinoma (SCC) group (5.27 kPa vs. 3.44 kPa, P = 0.042). The TS also showed significant difference between poorly and well/moderately differentiated CC (5.21 kPa vs. 3.47 kPa, P = 0.038), CC patients and healthy participants (4.18 kPa vs. 1.99 kPa, P < 0.001). The cutoff value of TS to discriminate ECA from SCC was 4.10 kPa (AUC: 0.80), while it was 4.42 kPa to discriminate poorly from well/moderately differentiated CC (AUC: 0.83), and 2.25 kPa to distinguish normal cervix from CC (AUC: 0.88), respectively. There were no significant difference in G″, DR and ADC values between any subgroups except for comparison of healthy participants and CC patients (P = 0.001, P = 0.004, P < 0.001, respectively). Data conclusion3D MRE-assessed TS shows promise as a potential biomarker to preoperatively assess tumor grade and subtype of CC.

Expression Profiling of EMT Transcriptional Regulators ZEB1 and ZEB2 in Different Histopathological Grades of Oral Squamous Cell Carcinoma Patients.

Pakistan has a high burden of oral cancers, with a prevalence rate of around 9%. Oral Squamous Cell Carcinoma (OSCC) accounts for about 90% of oral cancer cases. Epithelial to Mesenchymal Transition (EMT) gets highly stimulated in tumor cells by adopting subsequent malignant features of highly invasive cancer populations. Zinc Finger E-Box binding factors, ZEB1 and ZEB2, are regulatory proteins that promote EMT by suppressing the adherent ability of cells transforming into highly motile cancerous cells. The present study aimed to analyze the expression of EMT regulators, ZEB1 and ZEB2, and their association with the clinicopathological features in different grades of OSCC patients. Tissue samples were collected for both case and control groups from the recruited study participants. Cancer tissues (cases) were collected from the confirmed OSCC patients, and healthy tissues (controls) were collected from third-molar dental extraction patients. The study participants were recruited with informed consent and brief demographic and clinical characteristics. The case group was further segregated with respect to the histological cancer grading system into well-differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD) squamous cell carcinoma (SCC) groups. RNA was extracted from the tissue samples for expression profiling of ZEB1 and ZEB2 genes through quantitative real-time PCR (qRT-PCR). All of the recruited participants had a mean age of 46.55 ± 11.7 (years), with most of them belonging to Urdu speaking ethnic group and were married. The BMI (kg/m2) of the healthy participants was in the normal range (18-22 kg/m2). However, BMI was found to be reduced with the proliferation in the pathological state of cancer. The oral hygiene of patients was better than the healthy participants, possibly due to the strict oral hygiene practice concerns of consultants. Every recruited OSCC patient had one or multiple addiction habits for more than a year. Patients reported health frailty (46.6%), unhealed mouth sores (40%), swallowing difficulties and white/reddish marks (80%), and restricted mouth opening (64.4%). Furthermore, 82.2% of the recruited patients observed symptoms within 1-12 months, and buccal mucosa was the most exposed tumor site among 55.6% of the patients. Expression profiling of EMT regulators showed gradual over-expressions of ZEB1 (8, 20, and 42 folds) and ZEB2 (4, 10, and 18 folds) in respective histological cancer grades. High expressions of ZEBs have been significantly associated with cancer progression and poor health. However, no association was found between OSCC with other clinicopathological features when compared to healthy controls.

Immune microenvironment heterogeneity of concurrent adenocarcinoma and squamous cell carcinoma in multiple primary lung cancers

The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and five gene sets upregulated in the ADC group. Reactome enrichment analysis of differentially expressed genes showed that the immune function-related pathways, including programmed cell death, innate immune system, interleukin-12 family signaling, and toll-like receptor 2/4 pathways, etc. were significantly enriched. Transcriptomic TIME analysis, with mIHC in patient specimens and in vivo validation, showed tumor-infiltrating immune cells were significantly more enriched and diverse in ADC, especially CD8 + T cells. Our results revealed that the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions in MPLCs.

The expression of miR-21, HSP90a and gGASP-1 in serum of patients with lung cancer and their correlation with pathological subtypes.

To investigate the expression of miR-21, heat shock protein-90a (HSP90a) and G protein-coupled receptorrelated sorting protein 1(GASP-1) in the serum of lung cancer patients and their correlation with pathological subtypes. Eighty patients with lung cancer were included in the lung cancer group from May 2020 to May 2022, and 40 volunteers who underwent physical examination were randomly included in the control group according to the group ratio of 2:1. This ratio balances the need for a sufficiently large experimental group to detect significant effects with the practicality of recruiting a manageable control group. To ensure the validity of our findings, we meticulously calculated the sample size to achieve adequate statistical power, thus enabling us to draw reliable conclusions. Serum miR-21, HSP90a and GASP-1 levels of patients in the two groups were detected. We quantitatively assessed the serum levels of miR-21, HSP90a, and GASP1 in lung cancer patients and healthy volunteers. We employed enzyme-linked immunosorbent assay (ELISA) for HSP90a and GASP-1, and reverse transcription-polymerase chain reaction (RT-PCR) for miR-21, ensuring precise quantification. To explore the correlation between it and pathological subtypes, TNM stage and lymph node metastasis of lung cancer patients. TNM stands for Tumor, Node, and Metastasis. This system is widely used for staging cancer and describes the size and extent of the primary tumor (T), the absence or presence of cancer in nearby lymph nodes (N), and whether the cancer has spread to other parts of the body (M). The serum levels of miR-21, HSP90a and GASP1 in lung cancer group were higher than those in control group (P < 0.05). ROC curve analysis showed that serum miR-21, HSP90a and GASP-1 levels had certain value in the diagnosis of lung cancer, and their AUC values were 0.901, 0.874 and 0.865, respectively (P < 0.05). There was no difference in the relative expression level of serum miR-21 between squamous cell carcinoma group and adenocarcinoma group (P>0.05), but the levels of HSP90a and GASP-1 in adenocarcinoma group were higher than those in squamous cell carcinoma group (P < 0.05). There was no difference in the levels of serum miR-21, HSP90a and GASP-1 between stage I and stage II groups (P>0.05). The levels of serum miR-21, HSP90a and GASP-1 in stage III and stage IV groups were higher than those in stage I and stage II groups, and those in stage IV were higher than those in stage III group (P < 0.05). The serum levels of miR-21, HSP90a and GASP-1 in patients with metastasis were higher than those in patients without metastasis (P < 0.05). Our study concludes that there is a notable association between elevated serum levels of miR-21, HSP90a, and GASP-1 and lung cancer. However, it is crucial to acknowledge that these findings are preliminary and further statistical analysis is needed to strengthen these associations. Future studies with comprehensive statistical evaluation will be vital to validate these potential biomarkers for lung cancer diagnosis and prognosis.

Role of asprosin and meteorin-like peptide in progression of actinic keratosis to squamous cell carcinoma

ABSTRACT Squamous cell carcinoma (SCC) often develops from an underlying premalignant lesion. Factors that affect the progression of actinic keratosis (AK) to invasive SCC are not fully known. Asprosin (ASP) and meteorin-like peptide (METRNL) are adipokines that are involved primarily in glucose metabolism. We investigated the expression of ASP and METRNL in AK and SCC to evaluate the role of these adipokines in the development of SCC. We used 15 SCC specimens, 12 AK specimens and 12 healthy control skin specimens. ASP and METRNL protein expression in tumor and surrounding tissue was evaluated using immunohistochemistry. ASP expression in tumor tissue was significantly greater in the SCC group than in the control and AK groups, but it did not differ significantly between the AK and control groups. A positive correlation was observed for both ASP and METRNL expressions between tumor tissue and adjacent epidermis, hair follicles, sebaceous gland, eccrine gland, inflammatory cells and vascular structures. ASP and METRNL may exert pro-tumor effects toward development of invasive SCC. The expression intensity of ASP and METRNL can be used as a biomarker of risk of progression to SCC.

Advancing NSCLC pathological subtype prediction with interpretable machine learning: a comprehensive radiomics-based approach.

This research aims to develop and assess the performance of interpretable machine learning models for diagnosing three histological subtypes of non-small cell lung cancer (NSCLC) utilizing CT imaging data. A retrospective cohort of 317 patients diagnosed with NSCLC was included in the study. These individuals were randomly segregated into two groups: a training set comprising 222 patients and a validation set with 95 patients, adhering to a 7:3 ratio. A comprehensive extraction yielded 1,834 radiomic features. For feature selection, statistical methodologies such as the Mann-Whitney U test, Spearman's rank correlation, and one-way logistic regression were employed. To address data imbalance, the Synthetic Minority Over-sampling Technique (SMOTE) was utilized. The study designed three distinct models to predict adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Six different classifiers, namely Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, eXtreme Gradient Boosting (XGB), and LightGBM, were deployed for model training. Model performance was gauged through accuracy metrics and the area under the receiver operating characteristic (ROC) curves (AUC). To interpret the diagnostic process, the Shapley Additive Explanations (SHAP) approach was applied. For the ADC, SCC, and LCC groups, 9, 12, and 8 key radiomic features were selected, respectively. In terms of model performance, the XGB model demonstrated superior performance in predicting SCC and LCC, with AUC values of 0.789 and 0.848, respectively. For ADC prediction, the Random Forest model excelled, showcasing an AUC of 0.748. The constructed machine learning models, leveraging CT imaging, exhibited robust predictive capabilities for SCC, LCC, and ADC subtypes of NSCLC. These interpretable models serve as substantial support for clinical decision-making processes.

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review.

To review the outcomes of targeted therapy and immunotherapy in advanced conjunctival tumors, including conjunctival squamous cell carcinoma, conjunctival melanoma, and conjunctival lymphoma. A Pubmed database systematic search was performed between January 1999 and December 2022. The literature search was limited to studies published in English. This review included 142 patients with advanced malignant conjunctival tumors from 42 articles. In the conjunctival squamous cell carcinoma group, 2 cases of advanced conjunctival squamous cell carcinoma treated with epidermal growth factor receptor inhibitors showed significant tumor size improvement after 7.5 months of follow-up. Among 7 cases treated with systemic immunotherapy, 5 cases (72%) had complete response (CR), 1 case (14%) showed partial response (PR), and 1 case (14%) had stable disease (SD) after 16 months. In the conjunctival melanoma group, among 18 cases treated with combined v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated extracellular signal-regulated kinase inhibitors, 6 (33%) had CR, 5 (28%) had PR, 2 (11%) had SD, and 5 (28%) had progressive disease after 24.8 months of follow-up. Of 44 conjunctival melanoma cases treated with immunotherapy, 12 (28%) had CR, 9 (20%) had PR, 7(16%) had SD, and 16 (36%) had progressive disease after 14.2 months. Systemic Rituximab treatment for conjunctival lymphoma cases resulted in CR in 21 patients (63%), PR in 11 patients (33%), and SD in 1 patient (3%) after 20.5 months of follow-up. Intralesional Rituximab injections in 38 conjunctival lymphoma cases showed CR in 28 patients (75%), PR in 7 patients (19%), SD in 1 patient (2%), and progressive disease in 2 patients (4%) after 20.4 months of follow-up. Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.