Prognosis Of Squamous Cell Carcinoma Research Articles

Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression.

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.

Citrullinated Histone H3, a Marker for Neutrophil Extracellular Traps, Is Associated with Poor Prognosis in Cutaneous Squamous Cell Carcinoma Developing in Patients with Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs.

Serum mir-31-5p is a reliable biomarker in patients with oral squamous cell carcinoma and oral lichen planus

BackgroundMicroRNAs have been proposed as a novel regulatory biomarker for gene expression and early diagnosis of cancers. In this study, we evaluate the expression level of miR-31-5p in the serum of patients with oral squamous cell carcinoma, oral lichen planus, and a healthy control group to obtain a primary diagnostic biomarker.Materials and methodsSerum was collected from patients with oral lichen planus (n = 32), patients with oral squamous cell carcinoma (n = 35), and healthy subjects (n = 32). MicroRNA was isolated from serum and cDNA was made from it. Then, the quantitative and qualitative expression of miR-31-5p levels among the samples was checked by the qRT-PCR method.ResultsIn this study, three groups were quantitatively and qualitatively analyzed for miR-31-5p expression in serum. The results showed that there was a statistically significant correlation between the mean quantitative and qualitative expression of miR-31-5p among the three groups (P < 0.05).ConclusionsThe expression of miR-31-5p was significantly higher in patients with oral squamous cell carcinoma and oral lichen planus compared with healthy controls. MiR-31-5p can be considered as a biomarker in serum that could be potentially reliable in the diagnosis and prognosis of oral squamous cell carcinoma and also in the transformation of lichen planus.

Comparative evaluation of imaging methods for prognosis assessment in esophageal squamous cell carcinoma: focus on diffusion-weighted magnetic resonance imaging, computed tomography and esophagography.

To identify the most sensitive imaging examination method to evaluate the prognosis of esophageal squamous cell carcinoma (ESCC). Thirty patients with esophageal squamous cell carcinoma (ESCC) participated in the study and underwent chemoradiotherapy (CRT). They were divided into two groups based on their survival status: the survival group and non-survival group. The diagnostic tests were utilized to determine the most effective imaging examination method for assessing the prognosis. 1. There were no significant differences in tumor length shown on esophagography or computed tomography (CT) or the maximal esophageal wall thickness shown on CT at the specified time points between the two groups. 2. The tumor length on diffusion-weighted imaging (DWI) in the survival group was significantly lower than in the non-survival group at the end of the sixth week of treatment (P=0.001). The area under the ROC curve was 0.840 (P=0.002), and the diagnostic efficiency was moderately accurate. 3. The apparent diffusion coefficient (ADC) values of the survival group were significantly higher than those in the non-survival group at the end of the fourth week and sixth week of treatment (both P<0.001). Areas under the curve were 0.866 and 0.970, with P values of 0.001 and <0.001 and good diagnostic accuracy. Cox regression analyses indicated the ADC at the end of the sixth week of treatment was an independent risk factor. Compared with esophagography and CT, DW-MRI has certain advantages in predicting the prognosis of ESCC.

A signature of four ferroptosis-related genes in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) prognosis has not improved significantly in the past few decades, and more effective treatments are needed to be explored. Ferroptosis is a newly discovered kind of regulated cell death in recent years, which is related to tumor immunity and can used to treat tumors. Therefore, the prognostic value of ferroptosis-related genes in laryngeal cancer needs further clarification. In this study, the mRNA expression profile data of LSCC were downloaded from the public database. After identifying ferroptosis-related differentially expressed genes (FDGs), we explored the role of these genes through functional enrichment analysis. FDGs with prognostic significance were identified by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. By calculating the risk score, we constructed a prognostic model. Kaplan-Meier (K-M) analysis, the receiver operating characteristic (ROC) curves, and the nomogram were utilized to investigate this model. Public databases and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify the expression of model genes. The model consisting of four FDGs was acknowledged to be a self-determining predictor of prognosis. The K-M survival curves and the ROC curves confirmed the model's predictive ability. The C index (0.805) indicates that the nomogram has a good predictive ability. In vitro studies have confirmed the differential expression of the four FDGs. We identified a novel ferroptosis-related gene signature for predicting prognosis in LSCC.

Impact of histopathological parameters in prognosis of oral squamous cell carcinoma

AbstractObjectiveSquamous cell carcinomas comprise approximately 90% of all oral malignancies. There is a wide geographical variation in the incidence of oral cancer, with South and South East Asia (SSEA) accounting for almost two third of new cases. The prognosis of oral cancer is influenced by a vast array of factors including demographic, clinical, histopathological and molecular factors. The objective this review is to analyse the impact of histopathological features assessed in hematoxylin and eosin stained sections on the prognosis of OSCC.Materials and MethodsMedline and Scopus data base search was performed in order to identify related articles on histopathological parameters in predicting prognosis of oral squamous cell carcinoma. The primary emphasis is on the studies conducted in SSEA, with an accompanying comparison of their findings with those from research conducted in other parts of the world.ResultsIt has been shown that the number of studies conducted in SSEA is not proportionate to the high prevalence of Oral Cancer in the region. There is no significant difference between the findings from SSEA compared to the rest of the world. It is clearly shown that most histopathological parameters can be accurately used to predict nodal metastasis and prognosis.ConclusionsHistopathological parameters can be used reliably in planning treatment of Oral cancer. Clinicians should combine clinical and histopathological parameters in drawing treatment plan for Oral Cancer.

Elucidating prognosis in cervical squamous cell carcinoma and endocervical adenocarcinoma: a novel anoikis-related gene signature model.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most prevalent gynecologic malignancies globally. The prognosis is abysmal once cervical cancer progresses to lymphatic metastasis. Anoikis, a specialized form of apoptosis induced by loss of cell adhesion to the extracellular matrix, plays a critical role. The prediction model based on anoikis-related genes (ARGs) expression and clinical data could greatly aid clinical decision-making. However, the relationship between ARGs and CESC remains unclear. ARGs curated from the GeneCards and Harmonizome portals were instrumental in delineating CESC subtypes and in developing a prognostic framework for patients afflicted with this condition. We further delved into the intricacies of the immune microenvironment and pathway enrichment across the identified subtypes. Finally, our efforts culminated in the creation of an innovative nomogram that integrates ARGs. The utility of this prognostic tool was underscored by Decision Curve Analysis (DCA), which illuminate its prospective benefits in guiding clinical interventions. In our study, We discerned a set of 17 survival-pertinent, anoikis-related differentially expressed genes (DEGs) in CESC, from which nine were meticulously selected for the construction of prognostic models. The derived prognostic risk score was subsequently validated as an autonomous prognostic determinant. Through comprehensive functional analyses, we observed distinctimmune profiles and drug response patterns among divergent prognosticstratifications. Further, we integrated the risk scores with the clinicopathological characteristics of CESC to develop a robust nomogram. DCA corroborated the utility of our model, demonstrating its potential to enhance patient outcomes through tailored clinical treatment strategies. The predictive signature, encompassing nine pivotal genes, alongside the meticulously constructed nomogram developed in this research, furnishes clinicians with a sophisticated tool for tailoring treatment strategies to individual patients diagnosed with CESC.

Deciphering COPS5 influence on immune infiltration and prognosis in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is a widespread malignancy originating from the mucous epithelium of the oral cavity, pharynx, and larynx. Despite advances in diagnostic and therapeutic modalities, the prognosis of HNSCC remains challenging. This study investigates the intricate relationship among COPS5, immune infiltration patterns, and prognostic implications in HNSCC. Through comprehensive analyses of 519 HNSCC cases from TCGA and single-cell data from the GEO database, we utilize the CIBERSORT algorithm to discern immune cell dynamics influenced by COPS5 expression. Notably, Treg cells emerge as a central point in the interplay between COPS5 and immune modulation. Further analyses, encompassing differential gene expression, immune-related gene set enrichment, and protein-protein interaction networks, elucidate the molecular landscape associated with COPS5 in HNSCC. A prognostic risk model, incorporating CD27, TNFRSF4, FADD, and PSMD14, is formulated and validated across diverse datasets. The model demonstrates robust predictive power, underscoring its potential as a valuable prognostic tool. These genes, essential for immune regulation and cell cycle control, provide insights into the intricate mechanisms influencing HNSCC progression. In conclusion, this study not only reveals the impact of COPS5 on immune dynamics in HNSCC but also introduces a concise and effective prognostic model.

The significance of CD4+ and CD8+ T lymphocyte infiltration in esophageal squamous cell carcinoma.

To investigate the relationship between the abundance of CD4+ and CD8+ T cells in the tumor microenvironment and the prognosis of patients with esophageal squamous cell carcinoma, and to analyze their correlation and explore its clinical value. In total, we enrolled 120 cases of esophageal squamous cell carcinoma diagnosed. The abundance of CD4+ and CD8+ T lymphocytes in the tissue specimens of esophageal cancer was examined by immunohistochemistry. We measured the correlation between the abundance of CD4+ and CD8+ T lymphocytes and the clinical and pathological characteristics and prognosis of esophageal squamous cell carcinoma. The tissue abundance of CD4+ T lymphocytes was closely related to tumor prognosis (P < 0.05). Similarly, there was a statistically significant relationship between the tissue abundance of CD8+ T lymphocytes and patients' prognosis (P < 0.05), indicating that a high abundance of CD8+ T lymphocytes predicts better prognosis in esophageal squamous cell carcinoma. Surprisingly, we found that a higher CD4+/CD8+ ratio predicted a better prognosis of esophageal squamous cell carcinoma. The tissue abundance of CD4+ and CD8+ T lymphocytes can serve as an important indicator for predicting the long-term survival of patients with esophageal squamous cell carcinoma. A high CD4+/CD8+ ratio may improve patients' prognosis through several pathways. The association of this ratio with clinical and pathological characteristics may explain the poor efficacy of immunotherapy in patients with esophageal cancer. These findings may help us find new targets for immunotherapy by exploring the immune microenvironment of esophageal squamous cell carcinoma.

D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors.

This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

Increased Immune Infiltration and Improved Prognosis of Head and Neck Squamous Cell Carcinoma Associated with Reduced Ancient Ubiquitous Protein 1 Gene Expression.

This study aimed to explore the molecular mechanism underlying the prognostic role of ancient ubiquitous protein 1 (AUP1) in head and neck squamous cell carcinoma (HNSCC) and its relationship with the tumor immune microenvironment. Various web resources were used to analyze the differential expression of AUP1 and its role in the HNSCC pathogenesis. A nomogram aimed at predicting 1-, 3-, and 5-year survival rates was developed based on the patient's clinicopathological characteristics and AUP1 expression pattern. Several algorithms and analytical tools were used to explore the correlation between AUP1 expression and sensitivity to immune checkpoint gene therapy by evaluating infiltrating immune cells in patients with HNSCC. Higher AUP1 mRNA and protein expression levels were observed in most tumors and HNSCC than in the normal tissues. High AUP1 expression was an independent predictive risk factor for the overall survival of patients as it was closely associated with the patients' T, M, clinical, and pathological stages and lymphovascular invasion in HNSCC. In conclusion, AUP1 is involved in the occurrence and progression of HNSCC, may be used as an independent prognostic factor in patients with HNSCC, and could serve as a potential intervention target to improve immunotherapy sensitivity in HNSCC.

A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. Due to the important role of mitochondrial metabolism in cancer progression, a clinical prognostic model based on mitochondrial metabolism and clinical features was constructed in this study to predict the prognosis of ESCC. Firstly, the mitochondrial metabolism scores (MMs) were calculated based on 152 mitochondrial metabolism-related genes (MMRGs) by single sample gene set enrichment analysis (ssGSEA). Subsequently, univariate Cox regression and LASSO algorithm were used to identify prognosis-associated MMRG and risk-stratify patients. Functional enrichment, interaction network and immune-related analyses were performed to explore the features differences in patients at different risks. Finally, a prognostic nomogram incorporating clinical factors was constructed to assess the prognosis of ESCC. Our results found there were differences in clinical features between the MMs-high group and the MMs-low group in the TCGA-ESCC dataset (P<0.05). Afterwards, we identified 6 MMRGs (COX10, ACADVL, IDH3B, AKR1A1, LIAS, and NDUFB8) signature that could accurately distinguish high-risk and low-risk ESCC patients. A predictive nomogram that combined the 6 MMRGs with sex and N stage to predict the prognosis of ESCC was constructed, and the areas under the receiver operating characteristic (ROC) curve at 1, 2 and 3 years were 0.948, 0.927 and 0.848, respectively. Finally, we found that COX10, one of 6 MMRGs, could inhibit the malignant progression of ESCC in vitro. In summary, we constructed a clinical prognosis model based on 6 MMRGs and clinical features which can accurately predict the prognosis of ESCC patients.

PLA2G2D and CHIT1: Potential biomarkers for immune infiltration and prognosis in cervical squamous cell carcinoma

PLA2G2D and CHIT1: Potential biomarkers for immune infiltration and prognosis in cervical squamous cell carcinoma

Comparison of 5-year survival rate and analysis of prognostic factors influencing the prognosis of adenoid cystic carcinoma and squamous cell carcinoma of the maxillary sinus: based on the SEER database

Objective:To analyze the difference in 5-year survival between maxillary sinus adenoidal cystic carcinoma（maxillary sinus adenoid cystic carcinoma, MSACC） and squamous cell carcinoma（maxillary sinus squamous cell carcinoma, MSSCC） using the National Cancer Institute's Surveillance, Epidemiology, and End. Results:database（SEER） and to explore the factors associated with the prognosis of the two tumors. Methods:The data of 161 patients with MSACC and 929 patients with MSSCC were collected from SEER database, and the 5-year overall survival rate（OS） and tumor specific survival rate（CSS） were compared between the two groups before and after propensity score matching. The forest map of multivariate Cox proportional hazard regression model was established to analyze the prognostic factors affecting the survival rate of patients with MSACC and MSSCC. Results:There were statistical differences in 5-year OS and CSS between MSACC and MSSCC before and after propensity score matching（P<0.001）. Multivariate regression analysis showed that age, side of the disease, lymph node metastasis, operation and radiotherapy were the influencing factors of OS in MSACC, while age and operation were the influencing factors of CSS. Age, race, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of OS of MSSCC. Age, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of CSS. Conclusion:The 5-year survival rate of MSACC is higher than that of MSSCC. Surgery plays a positive role in the prognosis of the two kinds of tumors. The analysis results can provide some reference for their survival expectations and treatment choices.

Molecular analysis of surgical margins with NGS to assess microscopic residual disease in early oral squamous cell carcinomas.

6063 Background: The prognosis of early oral squamous cell carcinomas (OSCC) is strongly correlated with local disease control. However, patients with T1-T2 OSCC operated with clear margins have a 5-year local relapse rate of 10 to 15%. An accurate evaluation of the microscopic residual disease (MRD) is therefore essential. Interestingly, innovative techniques have recently been developed to detect circulating tumor DNA. Methods: A prospective multicenter trial based on patients with T1-T2 OSCC treated surgically with clear margins, was designed to assess the feasibility of a molecular analysis (tetranucleotide instability) of these margins to evaluate a potential MRD while adapting the postoperative strategy (NCT00232960). We, then, evaluate the feasibility of detecting MRD in the margins by identifying specific molecular abnormalities in the primary tumor with Whole Exome Sequencing (WES) and explore them in margins with deep target NGS panel (TGS) and digital PCR (dPCR) for hotspot mutations. Results: 310 patients were included initially with 216 tumor/margins samples available for molecular analysis. After a standard pathologic analysis, all surgical margins were negative.Median follow-up was 58 months [30;83]. Tumor was informative for tetranucleotide instability analysis in 63% of cases. Positive molecular margins were observed in 17.3% of cases, leading to a postoperative treatment (surgery or radiotherapy). In informative tumors, molecularly driven treatment seemed to lower the 5-year local recurrence rate from 14.1% to 6.4% (p=0.15). Among this initial cohort, 108 primary tumors were secondarily screened by WES to find mutations of interest, with an informativity rate of 75%. Positive molecular results (TGS or dPCR), with at least one positive margin, were observed in 19.4% of patients. Then, analyzing retrospectively the oncologic outcomes, we observed a significant benefit for local control at 5 years for patients with TGS-dPCR negative results in all margins compared to pathologic negative margins (91.7% versus 64.1%, p=0.02). Conclusions: To our knowledge, this is the first report of local MRD assessment after surgery using NGS.Molecular analysis of resection margins for early OSCC lead to a better evaluation of MRD and personalized postoperative decision making to improve local control. Clinical trial information: NCT00232960 .

TTCC-2022-01: Niraparib and dostarlimab in locally-advanced head and neck squamous cell carcinoma treated with (chemo) radiotherapy (RADIAN).

TPS6125 Background: The prognosis of locally-advanced head and neck squamous cell carcinoma (LA-HNSCC) remains poor, with a 60% 5-year overall survival (OS) rate despite curative-intent therapies. Treatment intensification strategies with antiPD-(L)1 agents given concurrently to (chemo)radiotherapy (CRT) have failed to improve survival. New radiosensitizing agents such as PARP inhibitors have shown encouraging results in early studies, and are of special interest in cisplatin-unfit patients (pts) (Moutafi et al. 2021). Beyond radiation sensitization, PARP inhibition is predicted to trigger immune responses via STING pathway activation, and synergize with anti-PD-(L)1 agents (Sen T et al., 2019). We hypothesize that niraparib will enhance antitumor immune responses when combined with dostarlimab before and after definitive CRT and will boost RT response ultimately leading to higher disease-free survival (DFS). Methods: Trial design: RADIAN is an investigator-initiated, multi-center, non-randomized two-cohort phase 1b study of niraparib and dostarlimab in LA-HNSCC pts candidates for CRT (cohort A) or RT alone (cohort B – cisplatin unfit). Dostarlimab 500mg is given intravenously 3 weeks(w) before RT and then q/3w starting w4 post-RT for up to 14 cycles. Niraparib 200 or 300mg is given orally once daily 1w after dostarlimab until start of CRT (cohort A) or continuously until last dose of RT (Cohort B) and then continuously in 3w cycles from w4 post-RT for up to a year (14 cycles). Intensity-modulated RT (70 Grays:2Gray/fraction) and high-dose cisplatin are given as per standard-of-care. Study procedures include collection of baseline archival or fresh tumor sample for molecular profiling, PD-L1 expression and immunophenotyping; serial blood samples for circulating tumor (ct) DNA and clinical/endoscopic photographs of the tumor (baseline, pre-niraparib, pre-RT, 12w post-RT, end-of treatment, and at progression). Imaging and follow-up procedures are conducted as per standard-of-care. Key eligibility criteria: untreated, stage III to IVB laryngeal, hypopharyngeal, HPV-negative oropharyngeal SCC (stage III only if HPV-positive), and stage IVB oral cavity SCC as per TNM 8th edition;adequate organ function; no autoimmune disorders; no immunosuppressive therapy. Study objectives: primary objective is to evaluate 1-year disease free survival. Secondary objectives: safety/tolerability including RT delay/completion; locoregional and distant control, event-free survival, OS and ctDNA dynamics correlation with efficacy endpoints. Sample size: 32 evaluable pts for correlative studies are planned for enrollment (16/cohort). It is expected that experimental treatment will provide an increase of efficacy of 0.64 in terms of HR (1-year DFS of 75.9 % in cohort A and 68.2% in cohort B). Study activation: Nov 11th 2023, with 2 pts enrolled as of Feb 6th 2024. Clinical trial information: NCT05784012 .

Laryngeal squamous cell carcinoma (LSCC) prognosis and machine learning insights.

e18058 Background: LSCC has seen a rise in cases and deaths over the past 30 years. Considering the evolving therapeutic options available in the treatment landscape, we evaluated treatment approaches and developed a machine learning (ML) model for patients with LSCC without distant metastasis. Methods: Data from 2000 to 2020 were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results database with localized/regional stages only, including the glottis (GC), supraglottic (SuGC), and subglottic (SGC). Patients who were not diagnosed based on histology, previous history of cancer or other concurrent malignancies, or unknown data were excluded. T-tests and chi-square tests were used to compare variables, while the Kaplan-Meier estimator, log-rank tests, and Cox regression analysis identified prognostic factors for overall survival (OS) and cancer-specific survival (CSS). We constructed prognostic models using ML algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: A total of 68,282 patients were included (43,434 with GC, 24,010 with SuGC, and 838 with SGC). Of the patients, 80.8% were males and 63.5% were over 60 years old and white (n=56,171). The tumors were &gt;2 cm in size (85.1%). The median patient age was 64 years, and the median tumor size was 3.2 cm. Of these patients, 36.5% underwent surgery with local tumor excision in 23.9 % and total laryngectomy in 5.7% of patients. White race, regional stage, large tumor size, and chemotherapy were poor prognostic factors for GC. Asian ethnicity, white race, and total laryngectomy were good prognostic factors for SuGC, whereas male sex and older age were poor prognostic factors. In terms of SCG "Surgery + adjuvant radiotherapy" was associated with better prognosis while regional and white race were associated with poor prognosis. Performance metrics for all ML algorithms are summarized in the Table. The factors that contributed the most to GC were the surgery type, stage, and age. Stage, surgery type, and race for SuGC and age, stage, and surgery type for SGC. Conclusions: ML models showed promising accuracy in predicting prognosis, highlighting the valuable contributions of factors such as surgery type, stage, age, and race. These findings offer insights into personalized treatment decisions and future research directions. [Table: see text]

Elucidating the Role of Let-7d-5p and OLR1 in the Progression and Prognosis of Oral Squamous Cell Carcinoma via FAK/P53 Signaling Axis.

Despite advances in oral squamous cell carcinoma (OSCC) diagnosis and treatment, the five-year survival rate remains low, underscoring the need for improved biomarkers and therapeutic strategies. This study investigated the role of let-7d-5p microRNA (miRNA) and its target gene OLR1 in OSCC, focusing on their implications in tumor progression, metastasis and potential as therapeutic targets. Employing next-generation sequencing and bioinformatic tools, we profiled differentially expressed miRNAs in metastatic OSCC cell lines, identifying let-7d-5p as a key down-regulated miRNA and OLR1 as a novel target of let-7d-5p. We validated this interaction using luciferase reporter assays and studied the biological effects of modulating let-7d-5p and OLR1 expression on OSCC cell proliferation, migration, invasion, and stemness. Additionally, we analyzed clinical data to establish the relevance of OLR1 expression in OSCC prognosis. Our findings revealed let-7d-5p as a potent suppressor of OSCC metastasis, primarily by targeting and down-regulating OLR1. OLR1-silencing reduced OSCC cell invasiveness, migration, and stemness, indicating its prominent role in tumor progression. Mechanistically, let-7d-5p modulates a signaling cascade involving FAK, SRC, PAXILLIN, and p53, influencing cellular apoptosis and chemoresistance. Clinically, elevated OLR1 expression significantly correlates with advanced OSCC stages and poorer survival rates, highlighting its potential as a prognostic marker and therapeutic target. Our study uncovers the significance of the let-7d-5p-OLR1 axis in OSCC pathogenesis, offering novel insights for future therapeutic interventions.

A novel fatty acid metabolism-related signature identifies MUC4 as a novel therapy target for esophageal squamous cell carcinoma

Fatty acid metabolism has been identified as an emerging hallmark of cancer, which was closely associated with cancer prognosis. Whether fatty acid metabolism-related genes (FMGs) signature play a more crucial role in biological behavior of esophageal squamous cell carcinoma (ESCC) prognosis remains unknown. Thus, we aimed to identify a reliable FMGs signature for assisting treatment decisions and prognosis evaluation of ESCC. In the present study, we conducted consensus clustering analysis on 259 publicly available ESCC samples. The clinical information was downloaded from The Cancer Genome Atlas (TCGA, 80 ESCC samples) and Gene Expression Omnibus (GEO) database (GSE53625, 179 ESCC samples). A consensus clustering arithmetic was used to determine the FMGs molecular subtypes, and survival outcomes and immune features were evaluated among the different subtypes. Kaplan–Meier analysis and the receiver operating characteristic (ROC) was applied to evaluate the reliability of the risk model in training cohort, validation cohort and all cohorts. A nomogram to predict patients’ 1-year, 3-year and 5-year survival rate was also studied. Finally, CCK-8 assay, wound healing assay, and transwell assay were implemented to evaluate the inherent mechanisms of FMGs for tumorigenesis in ESCC. Two subtypes were identified by consensus clustering, of which cluster 2 is preferentially associated with poor prognosis, lower immune cell infiltration. A fatty acid (FA) metabolism-related risk model containing eight genes (FZD10, TACSTD2, MUC4, PDLIM1, PRSS12, BAALC, DNAJA2 and ALOX12B) was established. High-risk group patients displayed worse survival, higher stromal, immune and ESTIMATE scores than in the low-risk group. Moreover, a nomogram revealed good predictive ability of clinical outcomes in ESCC patients. The results of qRT-PCR analysis revealed that the MUC4 and BAALC had high expression level, and FZD10, PDLIM1, TACSTD2, ALOX12B had low expression level in ESCC cells. In vitro, silencing MUC4 remarkably inhibited ESCC cell proliferation, invasion and migration. Our study fills the gap of FMGs signature in predicting the prognosis of ESCC patients. These findings revealed that cluster subtypes and risk model of FMGs had effects on survival prediction, and were expected to be the potential promising targets for ESCC.

TMErisk score: A tumor microenvironment-based model for predicting prognosis and immunotherapy in patients with head and neck squamous cell carcinoma

Tumor microenvironment (TME) is closely associated with the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). To investigate potential biomarkers for predicting therapeutic outcomes in HNSCC, we analyzed the immune and stromal status of HNSCC based on the genes associated with TME using the ESTIMATE algorithm. Immune and stromal genes were identified with differential gene expression and weighted gene co-expression network analysis (WGCNA). From these genes, 118 were initially selected through Cox univariate regression and then further input into least absolute shrinkage and selection operator (LASSO) regression analysis. As a result, 11 genes were screened out for the TME-related risk (TMErisk) score model which presented promising overall survival predictive potential. The TMErisk score was negatively associated with immune and stromal scores but positively associated with tumor purity. Individuals with high TMErisk scores exhibited decreased expression of most immune checkpoints and all human leukocyte antigen family genes, and reduced abundance of infiltrating immune cells. Divergent genes were mutated in HNSCC. In both high and low TMErisk score groups, the tumor protein P53 exhibited the highest mutation frequency. A higher TMErisk score was found to be associated with reduced overall survival probability and worse outcomes of immunotherapy. Therefore, the TMErisk score could serve as a valuable model for the outcome prediction of HNSCC in clinic.