scholarly journals Ferroptosis-associated gene SLC7A11 is upregulated in NSCLC and correlated with patient’s poor prognosis: An integrated bioinformatics analysis

Pteridines ◽  
2021 ◽  
Vol 32 (1) ◽  
pp. 106-116
Author(s):  
He Huang ◽  
Juan Liu ◽  
Haiyan Wu ◽  
Fang Liu ◽  
Xiaoxi Zhou
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Kegg Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Progression Free Survival ◽  
Ppi Network ◽  
Free Survival ◽  
Synonymous Substitutions

Abstract Objective Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, which was involved in the progression of malignant tumors including non-small cell lung cancer (NSCLC). Material/methods Ferroptosis inhibiting gene solute carrier family 7 member 11 (SLC7A11) mRNA expression was investigated in the database of TCGA and Oncomine and compared between the cancer tissue and the normal corresponding tissue of NSCLC patients. SLC7A11 gene mutation of NSCLC was investigated in the TCGA database by the online data analysis tool of Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. The protein–protein interaction (PPI) network of SLC7A11 and associated genes were constructed with the STRING database. Gene ontology (GO) and the KEGG pathway of genes involved in the PPI network were explored and demonstrated by a bubble plot. Progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) between SLC7A11high and SLC7A11low expression groups were compared and demonstrated by the survival curve. Results SLC7A11 mRNA was upregulated in cancer tissues compared to paired normal tissues in colorectal adenocarcinoma, esophageal squamous cell carcinoma, lung squamous cell carcinoma rectum adenocarcinoma and uterine corpus endometrial carcinoma. Missense and synonymous substitutions were 66.67% and 16.67% for lung squamous cell carcinoma. For lung adenocarcinoma, the missense and synonymous substitutions were 66.67% and 33.33% respectively. In the case of single nucleotide mutation, A>T, C>G, G>A, G>T for lung squamous cell carcinoma and G>T, C>A, G>A, T> for lung adenocarcinoma were the most common mutations in the SLC7A11 coding strand. Fifty-one genes were included in the PPI network with an edge number of 287, average node degree of 11.3 and local clustering coefficient of 0.694, which demonstrated that the PPI network was enriched significantly (p = 1.0 × 10−16). In terms of the KEGG pathway, the SLC7A11 and PPI-involved genes were mainly enriched in ferroptosis, NSCLC, pathways in cancer, tp53 signaling pathway, etc. The overall survival (OS) in the SLC7A11high group was significantly lower than those of SLC7A11low groups in NSCLC (HR = 1.15, 95% CI: 1.02–1.31, p = 0.027). However, the progression-free survival (PFS) (HR = 1.17, 95% CI: 0.97–1.42, p = 0.098) and postprogression survival (PPS) (HR = 1.00, 95% CI: 0.78–1.29, p = 0.97) between SLC7A11high and SLC7A11low expression groups were not statistically different. Conclusion SLC7A11 was upregulated in NSCLC and correlated with the patient’s poor overall survival. SLC7A11 may be a potential target for NSCLC treatment through the ferroptosis pathway.

scholarly journals Prognostic Analysis of Preoperative Inflammatory Biomarkers in Patients With Laryngeal Squamous Cell Carcinoma

2019 ◽  
Vol 99 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Youfang Xun ◽  
Maohua Wang ◽  
Haiyong Sun ◽  
Shujun Shi ◽  
Bing Guan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Progression Free Survival ◽  
Inflammatory Biomarkers ◽  
Distribution Width ◽  
Free Survival ◽  
Lymphocyte Ratio

Objective: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma. Methods: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma. Results: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival. Conclusions: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.

scholarly journals Real-world Treatment Patterns and Outcomes with Systemic Therapies in Unresectable Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma in Germany

2021 ◽  
Author(s):  
Felix Kramb ◽  
Christoph Doerfer ◽  
Andreas Meiwes ◽  
Karthik Ramakrishnan ◽  
Thomas Eigentler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Hazard Ratio ◽  
Free Survival

Advanced cutaneous squamous cell carcinoma is a challenge to treat. Conventional systemic treatment options include chemotherapy and epidermal growth factor receptor-inhibitors. The aim of this study was to assess clinical outcomes with systemic treatments in advanced cutaneous squamous cell carcinoma. Patients receiving systemic treatment at the Tübingen Dermato-Oncology centre between 2007 and 2017 were identified (n = 59). Median age was 76 years (interquartile range (IQR) 71–80 years), 83.1% of patients were male, 72.9% had metastatic cutaneous squamous cell carcinoma, and 27.1% had unresectable locally advanced cutaneous squamous cell carcinoma. During median follow-up of 52 weeks (IQR 27–97 weeks), overall response rate was 14.3%, and disease control rate was 53.6%. Median progression-free survival was 15 weeks (IQR 8–42 weeks), and median overall survival was 52 weeks (IQR 27–97 weeks). Patients receiving chemoradiation vs chemo­therapy alone showed better overall survival (hazard ratio 0.41, p = 0.014,) and progression-free survival (hazard ratio 0.42, p = 0.009); no differences were observed for metastatic cutaneous squamous cell carcinoma vs locally advanced cutaneous squamous cell carcinoma patients. Although chemotherapy and/or cetuximab showed limited outcomes in advanced cutaneous squamous cell carcinoma, such therapy may still be an option when anti-PD-1 treatment is contraindicated.

scholarly journals Expression of HDAC8 indicates poor prognosis of esophageal squamous cell carcinoma and progression to advanced stage

2019 ◽  
Vol 6 (1) ◽  
pp. 19-25
Author(s):  
Cheng Yufeng ◽  
Effat Un Nesa ◽  
Xuan Chen ◽  
Cong Wang ◽  
Xue Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Lymph Node Status ◽  
Nuclear Staining ◽  
Operating Characteristics ◽  
Free Survival

Background: We determined to assess the HDAC8 expression in esophageal squamous cell carcinoma (ESCC) patients and prognostic potential though there is only a little research contribution regarding HDAC8 to tumorigenesis of ESCC. Methods: The immunohistochemical expression of HDAC8 was investigated on tissue microarrays (TMAs) from 110 patients with esophageal squamous cell carcinoma.The nuclear staining intensity is calculated by the immune reactivity score ranging from (0-12) and divides them into two groups: no expression group and overexpression. Results: The median follow-up duration was 70 months. Highly regulated HDAC8 protein significantly predicted decreased 5-year overall survival (p = 0.001) and progression-free survival (p = 0.001) demonstrated by the log-rank test. Furthermore, HDAC8 protein acts as an independent prognostic factor for overall survival and progression-free survival, which determined after multivariate analyses. By Receiver operating characteristics (ROC) analysis, the value of HDAC8 was (0.63±0.54,p=0.04) according to advance cancer stage and (0.59±0.06,p=0.04) according to the lymph node status found in the Area under the curve (AUC). Conclusion: HDAC8 protein is highly regulated in ESCC tissues and potential prognostic indicator for diagnosing patients with decreased survival period.

Association of human papilloma virus status and response to radiotherapy in vulvar squamous cell carcinoma

2019 ◽  
Vol 30 (1) ◽  
pp. 100-106 ◽  
Author(s):  
Lily Proctor ◽  
Lien Hoang ◽  
Jocelyn Moore ◽  
Emily Thompson ◽  
Samuel Leung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Vulvar Squamous Cell Carcinoma ◽  
Papilloma Virus ◽  
Free Survival ◽  
Hpv Status

IntroductionVulvar squamous cell carcinoma develops through two separate pathways, associated with the presence or absence of high-risk human papilloma virus (HPV). The objective of this study was to evaluate treatment response and clinical outcomes in women with HPV-associated versus HPV-independent vulvar squamous cell carcinoma treated with primary radiation therapy, in order to determine the ability to use HPV status as a predictor of response to radiation therapy.MethodsThis was a retrospective cohort study combining data from British Columbia Cancer, Canada and Duke University, USA. Patients were included who had been treated with radiation therapy but excluded if they had received major surgical interventions. Immunohistochemistry for p16 (as a surrogate for high-risk HPV infection) and p53 was performed. We analyzed the univariable association between p16 status and clinico-pathological features and performed univariable survival analysis for p16.ResultsForty-eight patients with vulvar squamous cell carcinoma treated with primary radiation therapy were identified: 26 p16 positive/HPV-associated patients and 22 p16 negative/HPV-independent patients. p16 positive vulvar squamous cell carcinoma demonstrated a significantly improved overall survival (HR 0.39, p=0.03) and progression-free survival (HR 0.35, p=0.02). In women treated with definitive radiation therapy, p16 positivity was associated with improved overall survival (HR 0.29, p<0.01) and progression-free survival (HR 0.21, p<0.01). Among patients who received sensitizing chemotherapy, a significant association was observed with p16 positive tumors and overall survival (HR 0.25, p=0.03) and progression-free survival (HR 0.09, p<0.01).ConclusionThis study suggests that HPV status in vulvar squamous cell carcinoma has both prognostic and predictive implications, with increased radiosensitivity demonstrated in HPV-associated vulvar squamous cell carcinoma. Implications may include radiation dose de-escalation for HPV-associated vulvar squamous cell carcinoma and increased surgical aggressiveness for HPV-independent vulvar squamous cell carcinoma.

scholarly journals Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 258 ◽  
Author(s):  
Akifumi Uchida ◽  
Naohiko Seki ◽  
Keiko Mizuno ◽  
Yasutaka Yamada ◽  
Shunsuke Misono ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cell ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Lung Squamous Cell Carcinoma ◽  
Free Survival ◽  
Disease Free

In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to investigate the functional significance of miR-451a and to identify its targeting of oncogenic genes in LUSQ cells. Downregulation of miR-451a was confirmed in LUSQ clinical specimens, and low expression of miR-451a was significantly associated with poor prognosis of LUSQ patients (overall survival: p = 0.035, disease-free survival: p = 0.029). Additionally, we showed that ectopic expression of miR-451a significantly blocked cancer cell aggressiveness. In total, 15 putative oncogenic genes were shown to be regulated by miR-451a in LUSQ cells. Among these targets, high kinesin family member 2A (KIF2A) expression was significantly associated with poor prognosis (overall survival: p = 0.043, disease-free survival: p = 0.028). Multivariate analysis showed that KIF2A expression was an independent prognostic factor in patients with LUSQ (hazard ratio = 1.493, p = 0.034). Aberrant KIF2A expression promoted the malignant transformation of this disease. Analytic strategies based on antitumor miRNAs and their target oncogenes are effective tools for identification of novel molecular pathogenesis of LUSQ.

scholarly journals Nomogram based on SIS predicting the survival of non-surgical thoracic esophageal squamous cell carcinoma treated by IMRT

2021 ◽  
Author(s):  
Xingyu Du ◽  
Shuchai Zhu ◽  
Jing Dong ◽  
Ke Yan ◽  
Xiaobin Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Prognostic Factors ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Inflammatory Markers ◽  
Progression Free Survival ◽  
Data Set ◽  
Free Survival

Abstract Background: Several inflammatory markers have been reported to be associated with clinical outcomes in patients with esophageal squamous cell carcinoma (ESCC). This study was to evaluate several pre-radiotherapy serum inflammatory indicators, including the neutrophil / lymphocytes ratio (NLR), platelet / lymphocyte (PLR), systemic immune-inflammatory index (SII), systemic inflammation score(SIS), and compare which one has the highest predicted survival value. Finally, combining inflammatory markers with traditional prognostic factors, a new Nomogram model was developed to predict overall survival (OS) and progression-free survival (PFS) for ESCC patients receiving radiotherapy (RT) or chemoradiotherapy (CRT). Methods: This study retrospectively reviewed the data of 245 patients with thoracic esophageal squamous cell carcinoma (ESCC) underwent RT or CRT in the Fourth Hospital of Hebei Medical University from January 2013 to December 2015. The survival differences of these indexes were compared by the Kaplan-Meier method, and the univariate and the multivariate analyses were performed to determine these prognostic factors of overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional hazards regression models were used to create nomogram for OS and PFS.Results: 239 patients met the eligibility criteria. The estimated 1-, 3-, and 5-year OS and PFS rates were 74.6%, 36.8%, 26.5% and 58.4%, 31.3%, 20.5%, respectively, for the whole group. The difference in survival between OS and PFS was significant when univariate analysis were applied based on these inflammation-based measures. Multivariate analysis showed that tumor length, T stage, TNM stage, chemotherapy, SIS were predictive variables for OS and PFS in the multivariate model. The nomogram model established based on multivariate models of training data set had good predictive ability, the unadjusted C-index was 0.701 (95% CI, 0.662– 0.740) and 0.695 (95% CI, 0.656 - 0.734) for OS and PFS. Conclusions: This study show that SIS, as a comprehensive indicator of inflammation and nutrition, had the strongest predictive power for evaluating prognosis. Moreover, our nomogram can accurately predict OS and PFS after treatment and may provide guidance regarding adjuvant therapy and surveillance.

scholarly journals Prognostic Significance of PD-L1 Expression In Patients With Primary Oropharyngeal Squamous Cell Carcinoma: A Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jerry Polesel ◽  
Anna Menegaldo ◽  
Giancarlo Tirelli ◽  
Vittorio Giacomarra ◽  
Roberto Guerrieri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Free Survival ◽  
Hpv Status

BackgroundAt present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care.MethodsA systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I2 ranging from 0% for progression-free survival to 11% for overall survival.ConclusionsPD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.

scholarly journals Definitive chemoradiotherapy has comparable survival outcomes to esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: real world data

2021 ◽  
Author(s):  
Kentaro Sawada ◽  
Hiroki Yukami ◽  
Saori Mishima ◽  
Hisashi Fujiwara ◽  
Tomohiro Kadota ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Real World ◽  
Progression Free Survival ◽  
Real World Data ◽  
Free Survival

Abstract Background Recently, the JCOG0502 has shown a comparable efficacy of chemoradiotherapy and esophagectomy in patients with clinical T1N0M0 esophageal squamous cell carcinoma. However, few studies have compared the clinical outcomes of these treatments in esophageal squamous cell carcinoma patients (including elderly patients) based on real-world data. Methods This retrospective study determined real-world outcomes in patients who underwent chemoradiotherapy or esophagectomy, including those with clinical T1N0M0 esophageal squamous cell carcinoma, between 2009 and 2017 at the National Cancer Center Hospital East. Results Among a total of 156 patients, 120 and 36 patients underwent esophagectomy and chemoradiotherapy, respectively; 138, 12 and 6 patients had Eastern Cooperative Oncology Group performance status 0, 1, and 2, respectively; and 33 and 123 patients had clinical tumor depth MM-SM1 and SM2-SM3, respectively. In a median follow-up of 72 months, 5-year progression-free survival and overall survival were respectively 77.0% and 81.5% in the esophagectomy group and 74.4% and 82.6% in the chemoradiotherapy group (P = 0.48 and, P = 0.89). Moreover, no treatment-related death was detected in both groups. In elderly patients (75 years or older), 5-year progression-free survival and overall survival were not significantly different between esophagectomy and chemoradiotherapy groups (5-year progression-free survival: 72.3% vs. 81.8%, P = 0.38; 5-year overall survival: 76.9% vs. 81.8%, P = 0.59). Conclusions This real-world study confirms the results of a previous clinical trial, and the present findings support chemoradiotherapy as one of the standard treatment options in patients of all ages with clinical T1N0M0 esophageal squamous cell carcinoma.

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