Relapse Rates with Surgery Alone in HPV-Related Intermediate- and High-Risk-Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review

Our study aimed to develop an immune prognostic signature that could provide accurate guidance for the treatment of esophageal squamous cell cancer (ESCC). By implementing Single-Sample Gene Set Enrichment Analysis (ssGSEA), we established two ESCC subtypes (Immunity High and Immunity Low) in GSE53625 based on immune-genomic profiling of twenty-nine immune signature. We verified the reliability and reproducibility of this classification in the TCGA database. Immunity High could respond optimally to immunotherapy due to higher expression of immune checkpoints, including PD1, PDL1, CTLA4, and CD80. We used WGCNA analysis to explore the underlying regulatory mechanism of the Immunity High group. We further identified differentially expressed immune-related genes (CCR5, TSPAN2) in GSE53625 and constructed an independent two-gene prognostic signature we internally validated through calibration plots. We established that high-risk ESCC patients had worse overall survival (P=0.002, HR=2.03). Besides, high-risk ESCC patients had elevated levels of infiltrating follicle-helper T cells, naïve B cells, and macrophages as well as had overexpressed levels of some immune checkpoints, including B3H7, CTLA4, CD83, OX40L, and GEM. Moreover, through analyzing the Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk group demonstrated drug resistance to some chemotherapy and targeted drugs such as paclitaxel, gefitinib, erlotinib, and lapatinib. Furthermore, we established a robust nomogram model to predict the clinical outcome in ESCC patients. Altogether, our proposed immune prognostic signature constitutes a clinically potential biomarker that will aid in evaluating ESCC outcomes and promote personalized treatment.

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Topical oro-dispersible budesonide tablets for stricture prevention after near circumferential ESD for esophageal squamous cell cancer – a case report

Zeitschrift für Gastroenterologie ◽

10.1055/a-1409-1076 ◽

2021 ◽

Author(s):

Daniel Mathies ◽

Tsuneo Oyama ◽

Ingo Steinbrück ◽

Franz Ludwig Dumoulin

Keyword(s):

Case Report ◽

High Risk ◽

Endoscopic Resection ◽

Squamous Cell ◽

Squamous Cell Cancer ◽

Cell Cancer ◽

Complete Healing ◽

Esophageal Squamous Cell Cancer ◽

Stricture Formation ◽

Local Injections

Abstract Background Endoscopic resection is the treatment of choice for early esophageal cancers. However, resections comprising more than 70–80 % of the circumference are associated with a high risk of stricture formation. Currently, repetitive local injections and/or systemic steroids are given for prevention. Case report We present here the case of a 78-year-old male patient who had a near circumferential endoscopic submucosal dissection for a pT1a mm, L0, V0, R0, G2 esophageal squamous cell cancer. At the end of endoscopic resection, 80 mg of triamcinolone was injected locally. The patient was then treated with oro-dispersible budesonide tablets (2 × 1 mg/day) and nystatin (4 × 100 000 I.E.) for 8 weeks. This treatment resulted in complete healing without any stricture formation and did not result in any complications. Discussion Treatment with orodispersible budesonide tablets could help prevent strictures after large endoscopic resections in the esophagus.

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A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

BMC Cancer ◽

10.1186/s12885-021-08765-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Congyu Shi ◽

Shan Liu ◽

Xudong Tian ◽

Xiaoyi Wang ◽

Pan Gao

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Risk Group ◽

High Risk Group ◽

Mutation Model ◽

Therapeutic Responses

Abstract Background Tumor protein p53 (TP53) is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSC), and TP53 mutations are associated with inhibited immune signatures and poor prognosis. We established a TP53 mutation associated risk score model to evaluate the prognosis and therapeutic responses of patients with HNSC. Methods Differentially expressed genes between patients with and without TP53 mutations were determined by using data from the HNSC cohort in The Cancer Genome Atlas database. Patients with HNSC were divided into high- and low-risk groups based on a prognostic risk score that was generated from ten TP53 mutation associated genes via the multivariate Cox regression model. Results TP53 was the most common mutant gene in HNSC, and TP53 mutations were associated with immunogenic signatures, including the infiltration of immune cells and expression of immune-associated genes. Patients in the high-risk group had significantly poorer overall survival than those in the low-risk group. The high-risk group showed less response to anti-programmed cell death protein 1 (PD-1) therapy but high sensitivity to some chemotherapies. Conclusion The risk score based on our TP53 mutation model was associated with poorer survival and could act as a specific predictor for assessing prognosis and therapeutic response in patients with HNSC.

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A Four-gene Autophagy-related Prognostic Signature and Its Association With Immune Landscape in Lung Squamous Cell Carcinoma

10.21203/rs.3.rs-125355/v1 ◽

2020 ◽

Author(s):

Lumeng Luo ◽

Minghe Lv ◽

Xuan Li ◽

Tiankui Qiao ◽

Kuaile Zhao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Risk Score ◽

Squamous Cell ◽

Immune Suppression ◽

Risk Group ◽

Lung Squamous Cell Carcinoma ◽

High Risk Group ◽

Low Risk

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.

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