Integrated analysis identifies AQP9 correlates with immune infiltration and acts as a prognosticator in multiple cancers

AbstractAquaporin 9 (AQP9), as an aquaglyceroporin, is expressed in many immune cells and plays important role in tumor initiation and progression. However, the relationship between AQP9 and tumor-infiltrating cells, and its prognostic value in cancers still require comprehensive understanding. Herein, we aimed to elucidate the correlations of AQP9 with prognosis and immune infiltration levels in diverse cancers. We detected the expression and survival data of AQP9 through Oncomine, TIMER, Kaplan–Meier Plotter and PrognoScan databases. The correlations between AQP9 and immune infiltrates were analyzed in TIMER database. Our results found that high AQP9 expression was significantly correlated with worse prognosis in breast, colon and lung cancers, while predicted better prognosis in gastric cancer. Moreover, AQP9 had significant association with various immune infiltrating cells including CD8+ and CD4+ T cells, neutrophils, macrophages and dendritic cells (DCs), and diverse immune gene markers in BRCA, COAD, LUAD, LUSC and STAD. AQP9 was also significantly correlated with the regulation of tumor associated macrophages (TAM). These results indicate that AQP9 can play as a significant biomarker to determine the prognosis and the immune infiltrating levels in different cancers. It might also contribute to the development of the immunotherapy in breast, colon, lung and gastric cancers.

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CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family

10.21203/rs.3.rs-40048/v1 ◽

2020 ◽

Author(s):

Peipei Gao ◽

Ting Peng ◽

Canhui Cao ◽

Shitong Lin ◽

Ping Wu ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Tumor Microenvironment ◽

Immune Cells ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Markers ◽

Immune Infiltration ◽

Kaplan Meier ◽

The Relationship

Abstract Background: Claudin family is a group of membrane proteins related to tight junction. There are many studies about them in cancer, but few studies pay attention to the relationship between them and the tumor microenvironment. In our research, we mainly focused on the genes related to the prognosis of ovarian cancer, and explored the relationship between them and the tumor microenvironment of ovarian cancer.Methods: The cBioProtal provided the genetic variation pattern of claudin gene family in ovarian cancer. The ONCOMINE database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to exploring the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via Kaplan-Meier plotter. Immunologic signatures were enriched by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor microenvironment of ovarian cancer were investigated via Tumor Immune Estimation Resource (TIMER).Results: In our research, claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, we found that CLDN3, CLDN4, CLDN6, CLDN10, CLDN15 and CLDN16 were significantly correlated with overall survival of patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunologic signatures about B cell, CD4 T cell and CD8 T cell. What makes more sense is that CLDN6 and CLDN10 were found related to the tumor microenvironment. CLDN6 expression was negatively correlated with immune infiltration level in ovarian cancer, and CLDN10 expression was positively correlated with immune infiltration level in ovarian cancer. Further study revealed the CLDN6 expression level was negatively correlated with gene markers of various immune cells in ovarian cancer. And, the expression of CLDN10 was positive correlated with gene markers of immune cells in ovarian cancer.Conclusions: CLDN6 and CLDN10 were prognostic biomarkers, and correlated with immune infiltration in ovarian cancer. Our results revealed new roles for CLDN6 and CLDN10, and they were potential therapeutic targets in the treatment of ovarian cancer.

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Membrane tension sensing molecule-FNBP1 is a prognostic biomarker related to immune infiltration in BRCA, LUAD and STAD

BMC Immunology ◽

10.1186/s12865-021-00475-z ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Zixuan Wang ◽

Zixin Tian ◽

Xi Song ◽

Jun Zhang

Keyword(s):

Lung Adenocarcinoma ◽

Critical Role ◽

Expression Level ◽

Immune Checkpoints ◽

M2 Macrophage ◽

Immune Gene ◽

Gene Markers ◽

Immune Infiltration ◽

Infiltrating Cells ◽

Stomach Adenocarcinoma

Abstract Background Formin-binding protein 1/17 (FNBP1/FBP17), as a membrane-bound protein, is wildly expressed in eukaryotic cells and performs a critical role in tumor tumorigenesis and progression. However, the relationship between FNBP1 and immune infiltrating cells, prognostic value in patients still require comprehensive understanding. We purposed to explore the correlations of FNBP1 expression, prognosis and immune infiltration levels in various cancers. Method The expression and survival data of FNBP1 were collected from Oncomine, TIMER, GEPIA, Kaplan–Meier Plotter and PrognoScan databases. Correlations between FNBP1 and immune infiltrates were analyzed in TIMER and GEPIA databases. Results Compared with normal tissues, FNBP1 is significantly differentially expressed in a variety of tumor tissues. FNBP1 has significant and complex effects on the prognosis of kinds of cancers. High-expression was obviously correlated with better prognosis in breast carcinoma and lung adenocarcinoma, while worse prognosis in stomach adenocarcinoma. Besides, FNBP1 had a correlation with various immune infiltrating cells and diverse immune gene markers in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD). FNBP1 was also positively correlated with the adjustment of CD8+ cells, T cells, M2 macrophage, neutrophils, monocyte, Th1 cells, T regulatory cells (Treg) and Tumor-associated macrophages (TAMs). The expression level of FNBP1 is closely positively correlated with the expression level of multiple immune checkpoints in the three cancers. In addition, FNBP1 is significantly positively correlated with the expression levels of a variety of immunosuppressive molecules. Conclusion Our findings reveal FNBP1 can serve as a significant biomarker to influence the prognosis and the immune infiltrating levels in different cancers. The differential expression of FNBP1 might not only contribute to the judgment of metastatic and non-metastatic tumors but also in the immune escape by upregulating the expression of immune checkpoints.

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ATG101 as a Novel Prognostic Biomarker Related to Immunotherapy in Pan-cancer

10.21203/rs.3.rs-430028/v1 ◽

2021 ◽

Author(s):

Zijian Zhang ◽

Jinggang Mo ◽

Chong Jin ◽

Hao Jiang ◽

Zhongtao Liu ◽

...

Keyword(s):

Critical Role ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Immune Checkpoints ◽

Integrated Analysis ◽

Tumour Immunity ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

The Relationship ◽

Pan Cancer

Abstract Background: ATG101 plays a significant role in the occurrence and development of tumours by regulating autophagy. Our study aimed to research the correlation between the expression of ATG101 and tumour prognosis and its role in tumour immunity. Methods: First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, we used Kaplan–Meier curves for survival analysis. Next, we analysed the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints. Besides, we analysed the relationship between the expression of ATG101 and methyltransferase. Finally, we used GSEA to study the function of ATG101 in COAD and LIHC. Results: Integrated analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in most tumours. We found that that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in COAD and LIHC.Conclusions: Our study highlights the significance of ATG101 in the study of tumour immunity from a pan-cancer perspective.

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Gene Risk Signature of m6A Regulators, KIAA1429, YTHDF1, YTHDF2, METTL3 and Its Relationship with Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-47948/v1 ◽

2020 ◽

Author(s):

Jingjing Guo ◽

Liwei Wang ◽

Hanfeng Xu ◽

Chuandong Zhu ◽

Jianning Wang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Cox Regression ◽

Clinical Information ◽

High Risk Group ◽

Consensus Clustering ◽

Immune Infiltration ◽

Infiltrating Cells ◽

Cancer Tissues ◽

The Relationship

Abstract Background: Hepatocellular carcinoma (HCC) is a tumor of the digestive system with high mortality. N6-methyladenosine (m6A) is one of the most common forms of mRNA modification. Tumor neoantigens play an important role in anti-tumor immune response and predict the clinical response of immunotherapy. There are few studies on the relationship between m6A regulators and immune infiltrating cells. The objective of this study was to determine the gene expression and prognostic value of m6A regulators in hepatocellular carcinoma. Further, we explored the relationship between m6A regulators and immune-infiltrating cells.Methods: 13 m6A regulators expressions in 374 cancer tissues and 50 normal tissues were analyzed using RNA-seq data and clinical information in the TCGA database. Survival package was used to analyze the survival of patients in the two groups, and the corresponding clinical characteristics and gene expression were analyzed using univariate and multivariate Cox regression. We evaluated the expression of KIAA1429, YTHDF1, YTHDF2, and METTL3 in HCC and its correlation with TIICs using TIMER and CIBERSORT.Results: Most m6A regulators had higher expression levels in 374 cancer tissues. We confirmed two groups of HCC patients using a consensus clustering method. The prognosis of the cluster 1 group was poor compared with that of the cluster 2 group. The m6A regulators, KIAA1429, YTHDF1, YTHDF2, and METTL3 are highly expressed in the high-risk group of HCC. Furthermore, it was found that four m6A regulators (KIAA1429, YTHDF1, YTHDF2, and METTL3) are closely related to the clinicopathological characteristics and poor prognostic marker of hepatocellular carcinoma. We analyzed the correlation between KIAA1429, YTHDF1, YTHDF2, and METTL3 expression and the level of immune invasion of HCC.Conclusion: KIAA1429, YTHDF1, YTHDF2, and METTL3 as m6A regulators may regulate the tumor microenvironment through tumor immune infiltration cells to exert immune anti-tumor effects. KIAA1429, YTHDF1, YTHDF2, and METTL3 as molecular markers providing a new target for therapy of HCC in the further.

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A potential role for metastasis-associated in colon cancer 1 (MACC1) as a pan-cancer prognostic and immunological biomarker

Mathematical Biosciences and Engineering ◽

10.3934/mbe.2021413 ◽

2021 ◽

Vol 18 (6) ◽

pp. 8331-8353

Author(s):

Ye Hu ◽

◽

Meiling Wang ◽

Kainan Wang ◽

Jiyue Gao ◽

...

Keyword(s):

Colon Cancer ◽

Cell Function ◽

Immune Checkpoints ◽

Immune Infiltration ◽

Kaplan Meier ◽

Tumor Mutational Burden ◽

Cancer Types ◽

R Programming ◽

The Relationship ◽

Pan Cancer

<abstract> <sec><title>Background</title>Metastasis-Associated in Colon Cancer 1(<italic>MACC1</italic>) is a validated biomarker for metastasis and is linked to survival. Although extensive experimental evidence indicates an association between <italic>MACC1</italic> and diverse cancers, no pan-cancer analyses have yet been performed for this marker, and the role of <italic>MACC1</italic> in immunology remains unknown. </sec> <sec><title>Material and Methods</title>In our study, we performed the analysis of <italic>MACC1</italic> expression and its influence on prognosis using multiple databases, including TIMER2, GEPIA2, Kaplan-Meier plotter. <italic>MACC1</italic> promoter methylation levels were evaluated using the UALCAN database. Based on the TCGA database, we explored the relationship between <italic>MACC1</italic> and tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints using the R programming language. We evaluated the association between <italic>MACC1</italic> and immune infiltration via TIMER and UALCAN. </sec> <sec><title>Results</title>Our results revealed that abnormal DNA methylation may be an important cause for the different expression of <italic>MACC1</italic> across cancer types. Meanwhile, we explored the potential oncogenic roles of <italic>MACC1</italic> and found significant prognostic value. <italic>MACC1</italic> may be related to T-cell function and the polarization of tumor-associated macrophages, especially in STAD and LGG. Its expression was associated with immune infiltration and was found to be closely related to immune checkpoint-associated genes, especially CD274 and SIGLEC15, indicating that <italic>MACC1</italic> may be a potential immune therapeutic target for several malignancies. Our paper reveals for the first time the relationship between <italic>MACC1</italic> and cancer immunology. </sec> <sec><title>Conclusions</title><italic>MACC1</italic> might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target. </sec> </abstract>

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HSF2 is a Promising Prognostic Biomarker and is Correlated With Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-89953/v1 ◽

2020 ◽

Author(s):

Bihui Han ◽

Yanxiu Meng ◽

Yumei Fan ◽

Bing Liu ◽

Jiajie Hou ◽

...

Keyword(s):

Immune Cells ◽

Critical Role ◽

Enrichment Analysis ◽

Normal Liver ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Immune Infiltration ◽

Kaplan Meier ◽

The Relationship ◽

Kaplan Meier Plotter

Abstract BackgroundHepatocellular carcinoma (HCC) is one of the most common malignancies and ranks as the second leading cause of cancer-related mortality worldwide. Heat shock factor 2 (HSF2) is a transcription factor that plays a critical role in development, particularly corticogenesis and spermatogenesis. However, studies on the expression and prognostic value of HSF2 and its association with tumor-infiltrating immune cells in HCC are still rare. MethodsThe TCGA, Oncomine, UALCAN, HCCDB and HPA databases were used to investigate HSF2 expression in HCC. Kaplan-Meier plotter, GEPIA and HCCDB databases were used to evaluate the association of HSF2 with the prognosis of HCC patients. Genetic alteration of HSF2 was examined by the cBioPortal database. The mechanism was investigated with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GESA), and the relationship between HSF2 expression and immune infiltration was explored through the TIMER database and CIBERSORT algorithm.Results In the present study, we found that HSF2 expression was significantly upregulated in HCC compared with normal liver tissues. High HSF2 expression was associated with poor survival in HCC patients. GO, KEGG and GESA analyses demonstrated that HSF2 was associated with various signaling pathways, including the immune response. Notably, HSF2 expression was significantly correlated with the infiltration levels of different immune cells. HSF2 expression also displayed a significant correlation with multiple immune marker sets in HCC. ConclusionsIn summary, we explored the clinical significance of HSF2 and provided a therapeutic basis for the early diagnosis, prognostic judgment, and immunotherapy of HCC.

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NEFM DNA methylation correlates with immune infiltration and survival in breast cancer

Clinical Epigenetics ◽

10.1186/s13148-021-01096-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Dandan Li ◽

Wenhao Zhao ◽

Xinyu Zhang ◽

Hanning Lv ◽

Chunhong Li ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Gene Signature ◽

Normal Breast ◽

Macrophage Infiltration ◽

Immune Gene ◽

Transcriptional Expression ◽

Immune Infiltration ◽

Kaplan Meier ◽

Kaplan Meier Plotter

Abstract Background This study aims to determine whether NEFM (neurofilament medium) DNA methylation correlates with immune infiltration and prognosis in breast cancer (BRCA) and to explore NEFM-connected immune gene signature. Methods NEFM transcriptional expression was analyzed in BRCA and normal breast tissues using Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The relationship between NEFM DNA methylation and NEFM transcriptional expression was investigated in TCGA. Potential influence of NEFM DNA methylation/expression on clinical outcome was evaluated using TCGA BRCA, The Human Protein Atlas and Kaplan–Meier plotter databases. Association of NEFM transcriptional expression/DNA methylation with cancer immune infiltration was investigated using TIMER and TISIDB databases. Results High expression of NEFM correlated with better overall survival (OS) and recurrence-free survival (RFS) in TCGA BRCA and Kaplan–Meier plotter, whereas NEFM DNA methylation with worse OS in TCGA BRCA. NEFM transcriptional expression negatively correlated with DNA methylation. NEFM DNA methylation significantly negatively correlated with infiltrating levels of B, CD8+ T/CD4+ T cells, macrophages, neutrophils and dendritic cells in TIMER and TISIDB. NEFM expression positively correlated with macrophage infiltration in TIMER and TISIDB. After adjusted with tumor purity, NEFM expression weekly negatively correlated with infiltration level of B cells, whereas positively correlated with CD8+ T cell infiltration in TIMER gene modules. NEFM expression/DNA methylation correlated with diverse immune markers in TCGA and TISIDB. Conclusions NEFM low-expression/DNA methylation correlates with poor prognosis. NEFM expression positively correlates with macrophage infiltration. NEFM DNA methylation strongly negatively correlates with immune infiltration in BRCA. Our study highlights novel potential functions of NEFM expression/DNA methylation in regulation of tumor immune microenvironment.

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FCGR1A Serves as a Novel Biomarker and Correlates With Immune Infiltration in Four Cancer Types

10.21203/rs.3.rs-38062/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jili Xu ◽

Yong Guo

Keyword(s):

Overall Survival ◽

T Cell ◽

Differential Expression Analysis ◽

Renal Clear Cell Carcinoma ◽

High Expression ◽

Immune Gene ◽

Gene Markers ◽

Immune Infiltration ◽

Normal Tissues ◽

Cancer Types

Abstract Background: FCGR1A encodes a protein that plays an important role in the immune response. The prognosis and tumor immune infiltration of FCGR1A in heterogeneous tumors remains unclear.Methods: Differential expression analysis of FCGR1A between tumor and normal tissues and the difference in overall survival (OS) among different cancer types were performed by Gene Expression Profiling Interactive Analysis (GEPIA). The correlation between FCGR1A and cancer immune infiltration or immue gene markers was completed through Tumor Immune Estimation Resource (TIMER) site. Results: FCGR1A exhibited high expression in various cancer types. FCGR1A was significantly correlated with the overall survival (OS) of cervical and endocervical cancer (CESC), cholangiocarcinoma (CHOL), kidney renal clear cell carcinoma (KIRC) and skin cutaneous melanoma (SKCM) (P<.05). High expression of FCGR1A meant a better prognosis except for KIRC. FCGR1A showed significant differences at different stages of KIRC and SKCM (P<.05). Furthermore, FCGR1A was notably associated with immune infiltrating levels of CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell in the four cancers (P<.05). FCGR1A also showed close relevance with different immune gene markers. The copy number variation (CNV) of FCGR1A significantly influenced the abundance of immune infiltration in KIRC and SKCM. Conclusion: FCGR1A may be a potential prognostic biomarker and related to immune infiltration levels in diverse cancers, especially in CESC, CHOL, KIRC, and SKCM. Besides, FCGR1A may be involved in the activation, regulation or induction of immune cells.

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Identification of key survival genes of the tumor microenvironment and immune infiltration in head and neck squamous cell carcinoma

10.21203/rs.3.rs-283947/v1 ◽

2021 ◽

Author(s):

Min Wang ◽

Tao Lu ◽

Yanshi Li ◽

Min Pan ◽

Zhihai Wang ◽

...

Keyword(s):

Survival Analysis ◽

Tumor Microenvironment ◽

Head And Neck ◽

Stromal Cells ◽

Survival Data ◽

Expression Profiles ◽

Critical Role ◽

Functional Enrichment ◽

Immune Infiltration ◽

Kaplan Meier

Abstract Background: Head and neck cancer (HNC) are highly aggressive solid tumors with poor prognoses. The tumor microenvironment (TME) plays a critical role in angiogenesis, invasion, and metastasis of HNC. In the TME, immune and stromal cells influence tumor initiation, response, and therapy. Our study aimed to evaluate the progression and prognosis of HNC by analyzing the key genes involved in immunization and stromal cells. Methods: Gene expression profiles, demographics, and survival data were downloaded from the TCGA database. Patients with HNC were divided into high immune/stromal score groupss or low immune/stromal score groups based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) were identified via functional enrichment analysis and protein-protein interaction networks, and survival analysis based on DEGs was also performed.Results: A total of 522 patients with HNC were enrolled for analysis. The average age was 60.87, and one-third of the patients were HPV-positive. Kaplan-Meier survival analysis showed that patients' median survival time in the low-score group was shorter than that of the high-score group (625 vs. 680 days, log-rank, p = 0.1716). According to immune scores, 925 genes were upregulated, and 72 genes were downregulated in the high-score group compared with the low-score group. Top Gene Ontology terms identified that T-cell costimulation, regulation of immune response, and the external side of the plasma membrane were the most involved pathways. Moreover, Kaplan-Meier analysis revealed that 480 DEGs were upregulated in the high-immune scores group, and a total of 126 DEGs were significantly associated with poor survival. Besides, we identified the hub genes of DEGs through protein-protein interactions and found that PTPRC, CD247, and CD4 are associated with immune infiltration and all-cause mortality.Conclusions: We identified a series of TME‐related genes significantly associated with overall mortality; this information is crucial for further understanding the role of TME and immune infiltration in the prognosis of HNC.

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The expression landscape of JAK1 and its potential as a biomarker for prognosis and immune infiltrates in NSCLC

BMC Bioinformatics ◽

10.1186/s12859-021-04379-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Kaikai Shen ◽

Yuqing Wei ◽

Tangfeng Lv ◽

Yong Song ◽

Xiaogan Jiang ◽

...

Keyword(s):

Early Stage ◽

Immune Markers ◽

Immune Infiltration ◽

Normal Tissues ◽

Early Stage Nsclc ◽

Kaplan Meier ◽

Nsclc Patients ◽

Stage 1 ◽

The Relationship ◽

Kaplan Meier Plotter

Abstract Background Janus-activated kinase-1 (JAK1) plays a crucial role in many aspects of cell proliferation, differentiation, apoptosis and immune regulation. However, correlations of JAK1 with prognosis and immune infiltration in NSCLC have not been documented. Methods We analyzed the relationship between JAK1 expression and NSCLC prognosis and immune infiltration using multiple public databases. Results JAK1 expression was significantly decreased in NSCLC compared with that in paired normal tissues. JAK1 overexpression indicated a favourable prognosis in NSCLC. In subgroup analysis, high JAK1 expression was associated with a preferable prognosis in lung adenocarcinoma (OS: HR, 0.74, 95% CI from 0.58 to 0.95, log-rank P = 0.017), not squamous cell carcinoma. In addition, data from Kaplan–Meier plotter revealed that JAK1 overexpression was associated with a preferable prognosis in male and stage N2 patients and patients without distant metastasis. Notably, increased levels of JAK1 expression were associated with an undesirable prognosis in patients with stage 1 (OS: HR, 1.46, 95% CI from 1.06 to 2.00, P = 0.02) and without lymph node metastasis (PFS: HR, 2.18, 95% CI from 1.06 to 4.46, P = 0.029), which suggests that early-stage NSCLC patients with JAK1 overexpression may have a bleak prognosis. Moreover, multiple immune infiltration cells, including NK cells, CD8 + T and CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells (DCs), in NSCLC were positively correlated with JAK1 expression. Furthermore, diverse immune markers are associated with JAK1 expression. Conclusions JAK1 overexpression exhibited superior prognosis and immune infiltration in NSCLC.

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