Squamous Cell Carcinoma Group Research Articles

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

PurposeThis 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. MethodsAll consecutive patients with cervical GAS treated at our hospital from November 2009 to August 2021 were included. 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. ResultsOverall, 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). ConclusionThis 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.

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.

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

Background: 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. Methods: 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) Results: 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. Conclusion: 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

The expression of miR-21, HSP90α and GASP-1 in serum of patients with lung cancer and their correlation with pathological subtypes

Background: To investigate the expression of miR-21, heat shock protein-90α (HSP90α) and G protein-coupled receptor-related sorting protein 1(GASP-1) in the serum of lung cancer patients and their correlation with pathological subtypes. &#x0D; Methods: 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. Serum miR-21, HSP90α and GASP-1 levels of patients in the two groups were detected. To explore the correlation between it and pathological subtypes, TNM stage and lymph node metastasis of lung cancer patients. &#x0D; Results: The serum levels of miR-21, HSP90α and GASP-1 in lung cancer group were higher than those in control group (P &lt; 0.05). ROC curve analysis showed that serum miR-21, HSP90α 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 &lt; 0.05). There was no difference in the relative expression level of serum miR-21 between squamous cell carcinoma group and adenocarcinoma group (P&gt;0.05), but the levels of HSP90α and GASP-1 in adenocarcinoma group were higher than those in squamous cell carcinoma group (P &lt; 0.05). There was no difference in the levels of serum miR-21, HSP90α and GASP-1 between stage I and stage II groups (P&gt;0.05). The levels of serum miR-21, HSP90α 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 &lt; 0.05). The serum levels of miR-21, HSP90α and GASP-1 in patients with metastasis were higher than those in patients without metastasis (P &lt; 0.05). &#x0D; Conclusions: In patients with lung cancer, serum miR-21, HSP90α and GASP-1 levels were increased, which were associated with pathological subtypes, stage and lymph node metastasis, and had high diagnostic significance in the clinic.

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.

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.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageⅠA lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

Head and neck squamous cell carcinoma-specific prognostic signature and drug sensitive subtypes based on programmed cell death-related genes.

As a complex group of malignancies, head and neck squamous cell carcinoma (HNSC) is one of the leading causes of cancer mortality. This study aims to establish a reliable clinical classification and gene signature for HNSC prognostic prediction and precision treatments. A consensus clustering analysis was performed to group HNSC patients in The Cancer Genome Atlas (TCGA) database based on genes linked to programmed cell death (PCD). Differentially expressed genes (DEGs) between subtypes were identified using the "limma" R package. The TCGA prognostic signature and PCD-related prognostic genes were found using a least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis. The robustness of the LASSO analysis was validated using datasets GSE65858 and GSE41613. A cell counting kit-8 (CCK-8) test, Western blot, and real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) were used to evaluate the expression and viability of prognostic genes. Four molecular subtypes were identified in PCD-related genes. Subtype C4 had the best prognosis and the highest immune score, while subtype C1 exhibited the most unfavorable outcomes. Three hundred shared DEGs were identified among the four subtypes, and four prognostic genes (CTLA4, CAMK2N1, PLAU and CALML5) were used to construct a TCGA-HNSC prognostic model. High-risk patients manifested poorer prognosis, more inflammatory pathway enrichment, and lower immune cell infiltration. High-risk patients were more prone to immune escape and were more likely to be resistant to Cisplatin and 5-Fluorouracil. Prognosis prediction was validated in external datasets. The expression of CTLA4, CAMK2N1, PLAU and CALML5 was enhanced in CAL-27 and SCC-25 cell lines, and CALML5 inhibited CAL-27 and SCC-25 cell viability. This study shares novel insights into HNSC classification and provides a reliable PCD-related prognostic signature for prognosis prediction and treatment for patients with HNSC.

The Influence of the Exposome in the Cutaneous Squamous Cell Carcinoma, a Multicenter Case-Control Study.

The concept of exposome refers to the total of harmful and beneficial environmental exposures that can help predict the organism's biological responses over time. Ultraviolet radiation (UVR) from sun exposure has been recognized as the main etiological agent of skin cancer, and squamous cell carcinoma (SCC) is one most commonly associated with chronic exposure. However, in recent years, evidence suggests that lifestyle, environmental pollution, and contaminants in water and food can have an influence. To study the relationship between SCC and sun exposure, pollution, stress, and lifestyle in a Spanish cohort. A multicenter case-control study was carried out in which 13 dermatologists from different regions of Spain recruited cases and controls between April 2020 and August 2022. The group of cases were patients diagnosed with SCC and, as a control group, people who attended Dermatology consultations as companions with no history of skin cancer. A total of 62 patients with SCC and 126 controls were included (62.9% males, median age 76.46 (10.1) and 33.3%, median age 55.7 (15), respectively). The SCC group had experienced more outside work than the controls (75% vs. 22.4%, p < 0.001), less recreational exposure (sunbathing, p = 0.05, and outdoor sports, p = 0.01), and a lower annual income (p = 0.01), with an increase in tobacco exposure (p < 0.001), without differences in other carcinogens, such as ionizing radiation or chemical exposure. The control group had a higher daily screentime use (p < 0.001) and practiced more relaxation activities (p = 0.03). A higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with SCC (p < 0.05). Some chronic medications (anxiolytics, antidepressants, beta-blockers, statins, hydrochlorothiazide, ACE inhibitors, metformin, and omeprazole) were also statistically associated with SCC. Statistical significance for all aforementioned variables was maintained in the multivariate analysis (p < 0.05). The study found a significant association between SCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers promoting sun-safe behaviors and stress-reducing activities, in addition to adequate skin photoprotection in patients under certain medications associated with SCC.

Epithelial-mesenchymal transition changes in nonsmall cell lung cancer patients with early COPD.

Epithelial-mesenchymal transition (EMT) might be central to lung cancer development in smokers and COPD. We illustrate EMT changes in a broader demographic of patient groups who were diagnosed with nonsmall cell lung cancer (adenocarcinoma and squamous cell carcinoma). These included COPD current and ex-smokers, patients with small airway disease and normal lung function smokers compared to normal controls. We had access to surgically resected small airway tissue from 46 subjects and assessed for airway wall thickness and immunohistochemically for the EMT biomarkers E-cadherin, N-cadherin, S100A4, vimentin and epidermal growth factor receptor (EGFR). All tissue analysis was done with a computer and microscope-assisted Image-Pro Plus 7.0 software. Airway wall thickness significantly increased across all pathological groups (p<0.05) compared to normal controls. Small airway epithelial E-cadherin expression markedly decreased (p<0.01), and increases in N-cadherin, vimentin, S100A4 and EGFR expression were observed in all pathological groups compared to normal controls (p<0.01). Vimentin-positive cells in the reticular basement membrane, lamina propria and adventitia showed a similar trend to epithelium across all pathological groups (p<0.05); however, such changes were only observed in reticular basement membrane for S100A4 (p<0.05). Vimentin was higher in adenocarcinoma versus squamous cell carcinoma; in contrast, S100A4 was higher in the squamous cell carcinoma group. EGFR and N-cadherin expression in both phenotypes was markedly higher than E-cadherin, vimentin and S100A4 (p<0.0001). EMT is an active process in the small airway of smokers and COPD diagnosed with nonsmall cell lung cancer, contributing to small airway remodelling and cancer development as seen in these patients.

The influence of different sequences of vessel ligation on long-term survival during video-assisted thoracoscopic lobectomy for non-small cell lung cancer: A matched cohort study.

In lobectomy of patients with lung cancer, the principle of operation is to cut off the pulmonary vein first, but it is often not taken seriously in clinical practice. We conducted this research to compare the impact of different sequences of pulmonary vessel ligation on the long-term survival of patients. This cohort study included 1239 patients treated surgically with video-assisted thoracoscopic lobectomy from January 2015 to December 2019 at The Second Affiliated Hospital of Nanchang University. Survival and perioperative indicators were compared between a Vein-first group (VF) and an artery-first group. After matching, 364 patients were included in each group for analysis. VF was associated with better overall survival (hazard ratio: 1.96 [1.4~2.74], P < .0001) and disease-free survival (hazard ratio: 1.65 [1.22~2.24], P = .0011). Meanwhile, the survival advantage of VF was achieved in almost all subgroups, particularly in the pathological tumor node metastasis stage I-II group and squamous cell carcinoma group. We obtained no significant differences in perioperative indications (operation time, hospital stay, etc) between VF and artery-first group. With better overall survival and disease-free survival, especially for pathological stage I-II squamous cell carcinoma, vein-first ligation should be strictly observed in lobectomy for patients with non-small cell lung cancer.

Neoadjuvant cemiplimab and surgery for stage II–IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study

We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. Regeneron Pharmaceuticals and Sanofi.

Significant changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic.

The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database. This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology. In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period. 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic.

The expression of Th17/Treg in oral submucosal fibrosis carcinogenesis and the significance in the development of mucosal lesions.

It targets to explore the expression of Th17/Treg in oral submucous fibrosis (OSF) carcinogenesis and its significance in the development of mucosal lesions. In this research, 100 patients with OSF who visited our hospital for surgical treatment from March 2020 to April 2022 were selected. Based on pathological examination results, the patients were divided into 27 patients with oral leukoplakia (OK) group, 14 patients with oral lichen planus (OLP) group, 9 patients with oral squamous cell carcinoma (OSCC) group, and 50 patients with OSF group. It adopted flow cytometry (FC) to calculate the ratio of peripheral blood Th17 cells and Treg cells in four groups, and the Th17/Treg ratio was calculated; The area of oral mucosal lesions (OML) from patients was collected. It needs to compare the differences in Th17/Treg ratio and OML area among four groups and determine the correlation between indicators. ROC curve was used to analyze the diagnostic threshold of the Th17/Treg ratio for carcinogenesis. Except for the OK and OLP, it had statistical significance differences in Th17, Treg cells, and Th17/Treg ratio (P<0.001); The area of OML in the OK, OLP, and OSCC was higher than that in the simple OSF, with statistical significance (P<0.001); Th17 (%), Treg (%), and Th17/Treg all had direct ratio with the area of OML; The area of OML has directed ratio with the development of mucosal lesions (r>0, P<0.05); The areas under the ROC curve for patients with OSF combined with OK, OLP, or OSCC with Th17 (%), Treg (%), Th17/Treg, and OML area were 0.560, 0.986, 0.936, and 0.466, respectively. The expression of Th17/Treg is elevated in oral submucosal fibrosis and carcinogenesis. When mucosal lesions progress or become cancerous, the Th17/Treg ratio increases accordingly, and it has more clinical value than the increase in the OML area.

Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma.

Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood. This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions. With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable. Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.