Expression Profile and Prognostic Value of CXCR Family Members in Head and Neck Squamous Cell Carcinoma

Abstract Background: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). Methods: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). Results: CXCRs were differentially expressed in HNSCC. As shown by Kaplan Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. Conclusions: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

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Expression Profile and Prognostic Values of SMC Family Members in HCC

10.21203/rs.3.rs-635749/v1 ◽

2021 ◽

Author(s):

Wei Yan ◽

Dan-dan Wang ◽

He-da Zhang ◽

Jinny Huang ◽

Jun-Chen Hou ◽

...

Keyword(s):

Gene Family ◽

Expression Profile ◽

Proportional Hazards ◽

Wide Spectrum ◽

Clinical Stage ◽

Family Members ◽

Enrichment Analysis ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas

Abstract Background: The structural maintenance of chromosome (SMC) gene family, comprising 6 members, is involved in a wide spectrum of biological functions in many types of human cancers. However, there is little research on the expression profile and prognostic values of SMC genes in hepatocellular carcinoma (HCC). Based on updated public resources and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC. Methods and materials: The expression data of SMC family members were obtained from The Cancer Genome Atlas (TCGA). The prognostic values of SMC members and clinical features were identified. A gene set enrichment analysis (GSEA) was conducted to explore the mechanism underlying the involvement of SMC members in liver cancer. The associations between tumor immune infiltrating cells (TIICs) and the SMC family members were evaluated using the Tumor Immune Estimation Resource (TIMER) database. Results: Our analysis demonstrated that mRNA downregulation of SMC genes was common alteration in HCC patients. SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated in HCC. Upregulation of SMC2, SMC3 and SMC4, along with clinical stage, were associated with a poor HCC prognosis based on the results of univariate and multivariate Cox proportional hazards regression analyses. SMC2, SMC3 and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results indicated that SMC members participate in multiple biological processes underlying tumorigenesis. Conclusion: This study comprehensively analyzed the expression of SMC gene family members in patients with HCC. This can provide insights for further investigation of the SMC family members as potential targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3 and SMC4 may be an effective strategy for HCC therapy.

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Prognostic value of trafficking of regulatory T cells to tumors in head and neck cancer patients.

Journal of Global Oncology ◽

10.1200/jgo.2019.5.suppl.104 ◽

2019 ◽

Vol 5 (suppl) ◽

pp. 104-104

Author(s):

Hyun Chang ◽

Hyun Jun Hong ◽

Yongho Kim

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Head And Neck ◽

Prognostic Value ◽

Cox Regression ◽

Progression Free Survival ◽

The Cancer Genome Atlas ◽

Significant Prognostic Factor ◽

Immune Activity ◽

Prognostic Effect

104 Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.

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A Novel Prognostic Index Based on the Analysis of Glycolysis-Related Genes in Head and Neck Squamous Cell Carcinomas

Journal of Oncology ◽

10.1155/2020/7353874 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yuchao Liu ◽

Shihua Yin

Keyword(s):

Head And Neck ◽

Squamous Cell ◽

Prognostic Significance ◽

Prognostic Index ◽

Enrichment Analysis ◽

Prognostic Indicator ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Risk Patients

Aims. The preferential dependence on glycolysis as a pathway of energy metabolism is a hallmark of cancer cells. However, the prognostic significance of glycolysis-related genes in head and neck squamous cell carcinoma (HNSCC) remains obscure. The purpose of this study was to identify glycolysis-related genes of prognostic value in HNSCC. Results. Transcriptional and clinical data of 544 HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) dataset. By gene set enrichment analysis (GSEA) and by employing a univariate and subsequently a stepwise multivariate Cox proportional regression model, eight glycolysis-related genes of prognostic significance in HNSCC (KIF2A, JMJD8, HMMR, STC2, HK1, EXT2, GPR8, and STC1) were identified. The patients were clustered into two groups (high and low risk) based on the expression of these genes. High-risk patients had significantly a shorter overall survival than low-risk patients. Furthermore, a new prognostic indicator based on selected glycolysis-related genes was developed by multivariate Cox analysis that proved to be a better predictor of patient outcome compared to other clinical factors. Conclusion. Our findings provide new insights into the role of glycolysis in HNSCC. The identified genes predict the patient prognosis and might substantially contribute to the development of individualized treatments.

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High expression of PIMREG predicts poor survival outcomes and is correlated with immune infiltrates in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.11697 ◽

2021 ◽

Vol 9 ◽

pp. e11697

Author(s):

Feng Jiang ◽

Min Liang ◽

Xiaolu Huang ◽

Wenjing Shi ◽

Yumin Wang

Keyword(s):

Prognostic Value ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Gene Set Enrichment ◽

Gene Set ◽

Kaplan Meier ◽

Cancer Genome Atlas

Background PIMREG is upregulated in multiple cancer types. However, the potential role of PIMREG in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to explore its clinical significance in LUAD. Methods Using the Cancer Genome Atlas (TCGA) databases, we obtained 513 samples of LUAD and 59 normal samples from the Cancer Genome Atlas (TCGA) databases to analyze the relationship between PIMREG and LUAD. We used t and Chi-square tests to evaluate the level of expression of PIMREG and its clinical implication in LUAD. The prognostic value of PIMREG in LUAD was identified through the Kaplan–Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to screen biological pathways and analyze the correlation of the immune infiltrating level with the expression of PIMREG in LUAD. Results PIMREG was highly expressed in patients with LUAD. Specifically, the level of PIMREG gradually increased from pathological stage I to IV. Further, we validated the higher expression of PIMREG expressed in LUAD cell lines. Moreover, PIMREG had a high diagnostic value, with an -AUC of 0.955. Kaplan–Meier survival and Cox regression analyses revealed that the high expression of PIMREG was independently associated with poor clinical outcomes. In our prognostic nomogram, the expression of PIMREG implied a significant prognostic value. Gene set enrichment analysis (GSEA) identified that the high expression PIMREG phenotype was involved in the mitotic cell cycle, mRNA splicing, DNA repair, Rho GTPase signaling, TP53 transcriptional regulation, and translation pathways. Next, we also explored the correlation of PIMREG and tumor-immune interactions and found a negative correlation between PIMREG and the immune infiltrating level of T cells, macrophages, B cells, dendritic cells (DCs) , and CD8+ T cells in LUAD. Conclusions High levels of PIMREG correlated with poor prognosis and immune infiltrates in LUAD.

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EFNA3 Can Serve as Potential Prognostic Biomarker for Luad Patients: A Comprehensive Analysis of the Eph/Ephrin Family

10.21203/rs.3.rs-105232/v1 ◽

2020 ◽

Author(s):

Gang Hou ◽

Mingming Deng ◽

Run Tong ◽

Zhe Zhang ◽

Tao Wang ◽

...

Keyword(s):

Prognostic Value ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Synaptic Function ◽

Gene Set Enrichment Analysis ◽

Clinical Value ◽

Expression Levels ◽

Diagnosis And Prognosis ◽

Prognostic Analysis ◽

Kaplan Meier

Abstract Background: Ephrin receptors (Eph) and their ligands called ephrins, function in various disease processes. However, the specific mechanism of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear.Methods: Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. The Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Clinical LUAD tissue was analyzed by immunohistochemistry identifying the clinical value of identifying the ephrin-A3 protein. Weighted Co-expression Network Analysis (WGCNA) and Gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3.Results: EPHA10, EFNA3/4/5 and EPHB1/2 mRNA expression levels were significantly increased in LUAD. EFNB1/2 and EPHB6 expression levels were significantly decreased. Prognostic analysis showed that EFNA3, EFNB1/2, and EPHB2 expression were significant correlate with both overall survival (OS) and progression-free survival (PFS) in LUAD patients. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated as an independent risk prognosis factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. Additionally, higher expression of EFNA3 was significantly correlated with OS in pan-cancer patients.Conclusions: This study revealed the abnormal expression and prognostic value of Eph/Ephrin family members in LUAD. In addition, it is emphasized that EFNA3 may be a novel biomarker for the diagnosis and prognosis of LUAD patients.

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A Pyroptosis-Related LncRNA Signature for Predicting Prognosis and Treatment in Hepatocellular Carcinoma

10.21203/rs.3.rs-1060949/v1 ◽

2021 ◽

Author(s):

Yuhao Zhang ◽

Jiaxin Zhang ◽

Fengxian Wei ◽

Haodong Zhang ◽

Dongdong Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Value ◽

Immune Cell ◽

Cox Regression ◽

Expression Profiles ◽

Enrichment Analysis ◽

Clinical Treatment ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Immune Infiltration

Abstract Background: Hepatocellular carcinoma (HCC), which carries a very bad prognosis, is a common malignant tumor worldwide. This study aim to identify a pyroptosis-related long non-coding RNA(pyLncRNA) prognostic signature in HCC by integrated bioinformatics analysis. Methods: All expression profiles of HCC were obtained from The Cancer Genome Atlas (TCGA) and pyroptosis-related genes were from the GSEA website. After identified differentially expressed pyLncRNAs, univariate Cox regression and Lasso analysis were used to identify a pyroptosis-related LncRNAs prognositic signature(py-LPS). Internal validation was used to validate the prognostic value of the py-LPS via the Kaplan-Meier(K-M) curve and receiver operating characteristic(ROC) curve. Additional, we established the nomogram and analyzed the correlation between the signature and immune immune infiltration as well as clinical treatment. Result: 7 pyLncRNAs were established the signature for HCC prognosis. K-M curves exhibited the low risk group presented a markedly longer OS than the high. Clinical subgroups analysis based age, gender, grade and stage yielded the similar results. The signature had an independent prognostic value for HCC(p<0.001). Nomogram estimated one-, three- and five-year survival were 0.777, 0.741 and 0.709. Then, gene set enrichment analysis(GSEA) demostrated significant pathways. Futhermore, we found immune cell infiltration and immunotherapy targets was associated with the signature,which could provided clinical recommendations for chemotherapy.Conclusion: In this study, a novel pyroptosis-related LncRNAs porgnostic signature of HCC, correlated with immune infiltration, could predict the survival of HCC patients and give suggestions for clinical treatment.

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Infiltrative tumour growth pattern correlates with poor outcome in oesophageal cancer

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2020-000431 ◽

2020 ◽

Vol 7 (1) ◽

pp. e000431

Author(s):

Maelle Anciaux ◽

Pieter Demetter ◽

Roland De Wind ◽

Maria Gomez Galdon ◽

Sylvie Vande Velde ◽

...

Keyword(s):

Rna Sequencing ◽

Oesophageal Cancer ◽

Growth Pattern ◽

Prognostic Value ◽

Epithelial To Mesenchymal Transition ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Sequencing Data ◽

Mesenchymal Transition

ObjectiveOesophageal cancer (OEC) is an aggressive disease with a poor survival rate. Prognostic markers are thus urgently needed. Due to the demonstrated prognostic value of histopathological growth pattern (HGP) in other cancers, we performed a retrospective assessment of HGP in patients suffering from invasive OEC.DesignA first cohort composed of 89 treatment-naïve operated patients with OEC from The Cancer Genome Atlas (TCGA) public database was constituted, from which H&E images and RNA-sequencing data were retrieved. Next, a second cohort composed of 99 patients with OEC treated and operated in a Belgian hospital was established. H&E-stained sections and extracted tumorous RNA were obtained from the samples. HGP were assessed on H&E slides as infiltrative (IGP) or expansive (EGP). TCGA RNA-sequencing data were analysed through the gene set enrichment analysis and Cytoscape softwares. Real-time quantitative PCR (qPCR) experiments were performed to assess gene expression in the Belgian cohort.ResultsIGP patients displayed a grim prognosis compared with EGP patients, while IGP was found as associated with numerous lymphovascular emboli and perinervous infiltrations. Analyses of the TCGA expression data showed that angiogenesis, epithelial-to-mesenchymal transition (EMT) and inflammation were significantly upregulated in IGP compared with EGP samples. qPCR experiments of three genes appearing as highly upregulated in each pathway showed no difference in expression according to the HGP.ConclusionThe current study demonstrates the poor prognostic value carried by IGP in OC and suggests angiogenesis, EMT and inflammation as key carcinogenetic pathways upregulated in this pattern.

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Tumor ferroptosis status demonstrated vulnerability to chemotherapy and reflected immune-activation in colorectal cancer

10.21203/rs.3.rs-84128/v1 ◽

2020 ◽

Author(s):

Yang Lv ◽

QingYang Feng ◽

ZhiYuan Zhang ◽

Peng Zheng ◽

DeXiang Zhu ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

M1 Macrophage ◽

Central Molecule ◽

Ifn Γ ◽

Cox Analysis

Abstract Background: Existing studies for ferroptosis and prognosis in colorectal cancer (CRC) were limited. In this study, we aim to investigate the prognostic role of ferroptosis markers in patients with CRC and exploration of its micro-environmental distributions. Methods: A total of 911 patients from 2008 to 2013 with CRC were enrolled. Immunohistochemical staining was performed for CRC patients’ tissue microarray. Selection and prognostic validation of markers were based on mRNA data from the cancer genome atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed to indicate relative immune landmarks and hallmarks. Ferroptosis and immune contexture were examined by CIBERSORT. Survival outcomes were analyzed by Kaplan-meier analysis and cox analysis.Results: A panel of 42 genes was selected. Through mRNA expression difference and prognosis analysis, GPX4, NOX1 and ACSL4 were selected as candidate markers. By IHC, increased GPX4, decreased NOX1 and decreased FACL4 indicate poor prognosis and worse clinical characteristics. Ferroptosis score based on GPX4, NOX1 and ACSL4 was constructed and validated with high C-index. Low ferroptosis score can also demonstrate the better progression free survival and better adjuvant chemotherapy (ACT) responsiveness. Moreover, tumor with low ferroptosis score tend to be infiltrated with more CD4+ T cells, CD8+ T cells and less M1 macrophage. Finally, we found that IFN-γ was potentially the central molecule at the crossroad between ferroptosis and onco-immune response. Conclusion: Ferroptosis plays important role on CRC tumor progression, ACT response and prognosis. Ferroptosis contributes to immune-supportive responses and IFN-γ was the central molecule for this process.

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Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

Bioscience Reports ◽

10.1042/bsr20193212 ◽

2020 ◽

Vol 40 (2) ◽

Cited By ~ 1

Author(s):

Ying Lü ◽

Jing Zhang ◽

Lei Li ◽

Shun Li ◽

Zongguo Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Transcription Factor ◽

Cox Regression ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Peripheral Blood Mononuclear ◽

Free Survival ◽

E2f Transcription Factor

Abstract This report aimed to investigate the carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma (HCC). E2F8 expression level was compared in Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine. Survival analysis of E2F8 for HCC were conducted in Kaplan–Meier plotter. Correlations of E2F8 and clinico-pathological features were performed in TCGA. Enrichment of interacted and similar genes with E2F8 was evaluated in Gene Set Enrichment Analysis (GSEA) and Metascape. We found that E2F8 was significantly up-regulated in tumor tissues compared with nontumor tissues (all P < 0.01). Moreover, E2F8 was significantly overexpressed in peripheral blood mononuclear cell (PBMC) in HCC patients than that in healthy individuals (P < 0.001). Meta-analysis in Oncomine database confirmed that E2F8 was significantly higher in HCC tumors (P = 4.28E-08). Additionally, E2F8 elevation significantly correlated with overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progression-free survival (PFS) in HCC patients (all P < 0.01). E2F8 level was significantly higher in HCC patients with advanced neoplasm histologic grade, American Joint Committee on Cancer (AJCC) stage and α-fetoprotein (AFP) elevation (all P < 0.05). Cox regression model demonstrated that high E2F8 was an independent risk factor for OS and DFS in HCC patients (HR = 2.16, P = 0.003 and HR = 1.64, P = 0.002, respectively). Enrichment analysis revealed that genes interacted/similar with E2F8 were mainly enriched in cell cycle pathways/biological process. Conclusively, up-regulated in tumors, E2F8 might accelerate tumor progression and result in unfavorable outcomes in HCC patients.

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Association between MUC5B mutation and prognosis across solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13515 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13515-e13515

Author(s):

Qun Zhao ◽

Hong Zheng ◽

Wei Duan ◽

Chengcheng Li ◽

Wenzhuan Xie ◽

...

Keyword(s):

Solid Tumors ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Underlying Mechanism ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Major Constituent ◽

Cancer Antigen 125 ◽

Damage Repair ◽

Invasive Mucinous Adenocarcinoma

e13515 Background: MUC5B encodes Mucin 5B, which is a gel-forming mucin and a major constituent of mucus in the respiratory tract. Previous studies have revealed an increased expression of MUC5B in invasive mucinous adenocarcinoma (IMA) of the lung, indicating it may be involved in the tumorigenesis, and its family member MUC16, which encodes cancer antigen 125 (CA125), a biomarker for tumor diagnosis and the MUC16 mutation was reported to be associated with higher tumor mutation load, and a better survival outcomes in Gastric Cancer. However, the association between MUC5B mutation and prognosis has never been investigated in solid tumors. Methods: Whole-exome sequencing, RNA sequencing and clinical data for 27 types of solid tumors were downloaded from The Cancer Genome Atlas (TCGA). Associations between MUC5B mutation and prognosis were analyzed, and gene set enrichment analysis (GSEA) was used to investigate the underlying mechanism. Results: Among the 27 tumors, MUC5B mutation was associated with a superior disease specific survival (DSS) in Uterine Corpus Endometrial Carcinoma (UCEC) (HR, 0.32; 95% CI, 0.13-0.80; P = 0.01), Bladder Urothelial Carcinoma (BLCA) (HR, 0.43; 95% CI, 0.18-1.05; P = 0.06) and lung adenocarcinoma(LUAD) (HR, 0.44; 95% CI, 0.2-0.95; P = 0.03). MUC5B was also or tended to be associated with longer progression-free survival (PFS) and overall survival (OS) in UCEC (PFS: HR, 0.40; 95% CI, 0.23-0.70; P < 0.001; OS: HR, 0.57, 95% CI 0.31-1.03, P = 0.06), BLCA (PFS: HR, 0.40; 95% CI, 0.19-0.86; P = 0.02; OS: HR 0.42, 95% CI 0.20-0.90, P = 0.02) and LUAD (PFS: HR, 0.63; 95% CI, 0.38-1.06; P = 0.08; OS: HR 0.55, 95% CI 0.31-0.97, P = 0.04). However, MUC5B mutation was associated with poorer OS (HR 1.64, 95% CI 1.03-2.59, P = 0.03) and tended to be associated with poorer PFS (HR 1.56, 95% CI 0.95-2.57, P = 0.08) in Head and Neck squamous cell carcinoma (HNSC). MUC5B mutation was not associated with survival in other tumors. MUC5B mutation was associated with a higher TMB in UCEC, BLCA and LUAD, and GSEA revealed prominent enrichment of signatures related to DNA repair in MUC5B mutation group, compared to MUC5B wide-type group in UCEC (FDR < 0.05), BLCA (FDR < 0.05), and LUAD (FDR < 0.05), but not in HNSC. Conclusions: MUC5B mutation may be a potential predictor for better prognosis in UCEC, BLCA and LUAD, through potentiating DNA damage repair signaling. Identification of MUC5B mutation by genomic profiling provides a potentially novel and convenient approach for these patients to predict the prognosis, and refines patients' management in clinical practice.

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