scholarly journals Titin Mutation Is Associated With Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaona Xie ◽  
Yemeng Tang ◽  
Jueqi Sheng ◽  
Pingping Shu ◽  
Xiayan Zhu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Therapy ◽  
Gene Mutations ◽  
Lung Squamous Cell Carcinoma ◽  
Cancer Genome ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Number Of Patients

Lung squamous cell carcinoma (LUSC) is a leading cause of mobidity and mortality worldwide. Recently, there was a shift in the treatment pattern of immune therapy in LUSC patients; merely a small number of patients with non-small cell lung cancer (NSCLC) at advanced stages respond well to immune checkpoint blockade (ICB) therapy, and tumor mutation burden (TMB) is a valuable independent indicator of response to immune therapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immunocytes in LUSC are still unclear. In the present paper, our team analyzed the somatically mutated genes from the ICGC (International Cancer Genome Consortium) and TCGA (The Cancer Genome Atlas) datasets and discovered that 15 frequent gene mutations occurred in both cohorts, including ZFHX4, MUC16, FLG, TP53, LRP1B, TTN, SYNE1, RYR2, CSMD3, USH2A, MUC17, DNAH5, FAM135B, COL11A1, and RYR3. Interestingly, only mutated TTN was related to higher TMB and prognostic outcomes among the 15 mutated genes. Moreover, according to the CIBERSORT algorithm, we revealed that TTN mutation enhanced the antitumor immune response. In conclusion, TTN may have important clinical implications for relevant immune therapy of lung squamous carcinoma.

scholarly journals Development and validation of an individualized immune prognostic model in stage I–III lung squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qi-Fan Yang ◽  
Di Wu ◽  
Jian Wang ◽  
Li Ba ◽  
Chen Tian ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Model ◽  
Lung Squamous Cell Carcinoma ◽  
Risk Groups ◽  
Stage I ◽  
Tissue Samples ◽  
Mutation Burden

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

A seven long-noncoding RNA signature predicts prognosis of lung squamous cell carcinoma

2020 ◽  
Vol 14 (1) ◽  
pp. 53-63
Author(s):  
Shuai Li ◽  
Yue Teng ◽  
Min-Jie Yuan ◽  
Ting-Ting Ma ◽  
Jian Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Lung Squamous Cell Carcinoma ◽  
Mapk Signaling ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.

scholarly journals Identification of factors related to immunotherapy efficacy and prognosis in patients with advanced head and neck squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xuanli Xu ◽  
Rongrong Li ◽  
Lin Zhang ◽  
Guopei Zhu ◽  
Dandan Ren ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Gene Mutations ◽  
Neck Squamous Cell Carcinoma ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Mutation Burden

Abstract Background Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes. Methods Survival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy. Results Anti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients. Conclusion HNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.

Frequent Mutations in p53, CDKN2A, PTEN Genes in Lung Squamous Cell Carcinoma: A Next Generation Sequencing Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S141-S142
Author(s):  
H Xu ◽  
E Wei
Keyword(s):  
Squamous Cell Carcinoma ◽  
Next Generation Sequencing ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Targeted Therapies ◽  
Gene Mutations ◽  
Lung Squamous Cell Carcinoma ◽  
Next Generation ◽  
Frequent Mutations ◽  
Generation Sequencing

Abstract Introduction/Objective Targeted therapies have been successfully used for the treatment of lung adenocarcinoma but have not been implemented in the treatment of lung squamous cell carcinoma (SqCC). In order to better understand the underlying biology of SqCC, we present comprehensive Next Generation Sequencing (NGS) data via Cancerplex from SqCC. We have observed frequent mutations in p53, CDKN2A, PTEN, CDKN2B, and TGFBR2 genes together with few new rare gene mutations. Methods Twenty-one patients with diagnosis of Lung SqCC have been selected for Cancerplex assay (Kew, Inc., Waltham, MA). Formalin-fixed tissues from these patients were used for the assay. Neoplastic tissues with tumor content higher than 20% were micro-dissected from the blocks and NGS was performed with at least 50 ng DNA content and with a limit of detection of 10% mutant alleles. The depth of coverage was 500, and the size of the targeted region was 2.8 Mb. Results were compared with published databases. Results We have observed p53 mutations in 100% cases. p53 gene mutations included single point mutations with various coding protein mutations as well as splice variants. Mutations in CDKN2A is found in 47.6% of cases; PTEN mutations in 33.3% of cases; CDKN2B mutations in 28.6% of cases, and TGFBR2 in 28.6% of cases, which has been reported as actionable variants and actionable copy number variants. Conclusion Previous literatures have provided evidence that SqCC arising in different anatomical sites share common genomic mutation patterns. Our data partially supports this finding. We demonstrated p53, CDKN2A and PTEN are among the most commonly mutated genes in lung SqCC, while a few other genes mutations does not fit in this pattern. Apparently more studies need to be done to provide a more clear genetic landscape of SqCC, which would facilitate the development of targeted therapies.

Analysis of HYAL3 Gene Mutations in Chinese Lung Squamous Cell Carcinoma Patients

2013 ◽  
Vol 99 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Rong-xin Zhang ◽  
Jin-hai Zhu ◽  
Jiang Fan ◽  
Xiao-qi Ji
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Squamous Cell ◽  
Gene Mutations ◽  
Lung Squamous Cell Carcinoma ◽  
Smoking History ◽  
Normal Lung ◽  
Exon 2

Purpose In a previous study, we found a hyaluronidase 3 (HYAL3) gene mutation in exon 2 at position 188 by genome sequencing in a lung squamous cell carcinoma patient. The mutation results in substitution of serine for alanine. The aim of the study was to screen the HYAL3 gene mutation in Chinese lung squamous cell carcinoma patients and explore the correlation between mutation of HYAL3 with clinical and pathological characteristics in lung squamous cell carcinoma patients in China. Methods We applied polymerase chain reaction to examine the HYAL3 gene mutations in cancer tissues and their adjacent normal tissues from 39 cases of lung squamous cell carcinoma patients. Results 1) The incidence rate of HYAL3 mutation in 39 cases of lung squamous cell carcinoma was 10.26% (4/39) and none in adjacent normal lung tissues (0/39). 2) The mutations of HYAL3 in the 4 cases were all heterozygous: 3 of them were located in exon 1 (G-T) and one in exon 2 (G-T). 3) Mutations of the HYAL3 gene were not correlated with the distribution of patient gender, age, tumor size, histological grade, smoking history, TNM stage or distant metastasis ( P >0.05). The gene mutation was correlated with lymph node status ( P = 0.044). Conclusion Mutations of the HYAL3 gene are rare in Chinese lung squamous cell carcinoma patients and might contribute to lymph node metastasis.

Sign in / Sign up

Export Citation Format

Share Document