Decreased expression of JAK1 associated with immune infiltration and poor prognosis in lung adenocarcinoma

Abstract BackgroundHyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the relationships between HMMR and prognosis and tumor-infiltrating lymphocytes in lung adenocarcinoma remain unclear.MethodsHMMR expression was analyzed emoloyed the TIMER, GEPIA, UALCAN, CCLE databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases, the gene mutation of HMMR was analysis by the cBioportal and COSMIC databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.ResultsIn this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene, for instance, CD279, CD274, CTLA4, LAG3, PDCD1LG2, TIGIT and HAVCR2. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. Overall, this study emphasized the significance of HMMR in cancer progression and Immune infiltration of LUAD.ConclusionsWe demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.

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Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma

Journal of Translational Medicine ◽

10.1186/s12967-021-03031-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Songhua Cai ◽

Xiaotong Guo ◽

Chujian Huang ◽

Youjun Deng ◽

Longde Du ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Cancer Progression ◽

Poor Prognosis ◽

Risk Group ◽

Critical Role ◽

Differential Expression Analysis ◽

High Risk Group ◽

Prognostic Models ◽

Immune Infiltration

AbstractAngiogenesis is the process of capillary sprouting from pre-existing vessels and it plays a critical role in the carcinogenic process of lung adenocarcinoma (LUAD). However, the association of angiogenesis regulators with the prognosis and progression of LUAD needs to be further elucidated. In this study, we adopted differential expression analysis, Cox proportional hazards (PH) regression analysis and experimental validation to identify angiogenesis regulators correlated with a poor prognosis, immune infiltration and cancer progression in LUAD. These results showed that the diagnostic and prognostic models based on COL5A2 and EPHB2 served as independent biomarkers with superior predictive ability. The patients in the high-risk group exhibited a worse prognosis in the TCGA cohort (P < 0.001, HR = 1.72, 95% CI 1.28–2.30), GSE310210 cohort (P = 0.005, HR = 2.87, 95% CI 1.46–5.61), and GSE31019 cohort (P = 0.01, HR = 2.14, 95% CI 1.19–3.86) than patients in the low-risk group. The high prognostic risk patients had a higher TMB (P < 0.001); higher fractions of M0 macrophages, neutrophils, NK cells resting, and T cells CD4 memory activated (P < 0.05); and higher expression of immune checkpoints PD-1, PDL-1, PDL-2, and B7H3 (P < 0.001). Patients in the high-risk group were more sensitive to chemotherapeutic drugs and molecular targeted drugs such as cisplatin, doxorubicin, gefitinib, and bosutinib (P < 0.0001). In addition, inhibition of COL5A2 and EPHB2 effectively suppressed the proliferation and migration of LUAD cells. The current study identified angiogenesis regulators as potential biomarkers and therapeutic targets for LUAD and may help to further optimize cancer therapy.

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Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation

Lung Cancer ◽

10.1016/j.lungcan.2021.02.028 ◽

2021 ◽

Author(s):

Pablo Moreno-Ruiz ◽

Sara Corvigno ◽

Nienke C. te Grootenhuis ◽

Linnéa La Fleur ◽

Max Backman ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

P53 Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Prognosis Marker

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ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2021.03.014 ◽

2021 ◽

Author(s):

Weiyang Lou ◽

Wenlong Wang ◽

Jing Chen ◽

Shuqian Wang ◽

Yuan Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

High Expression ◽

Immune Infiltration

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Expression of nucleolar protein p120 predicts poor prognosis in patients with stage I lung adenocarcinoma

Annals of Oncology ◽

10.1023/a:1011617707999 ◽

2001 ◽

Vol 12 (8) ◽

pp. 1121-1125 ◽

Cited By ~ 13

Author(s):

Y. Saijo ◽

G. Sato ◽

K. Usui ◽

M. Sato ◽

M. Sagawa ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Poor Prognosis ◽

Nucleolar Protein ◽

Stage I

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Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

10.21203/rs.3.rs-219997/v1 ◽

2021 ◽

Author(s):

Zhenyu Zhao ◽

Boxue He ◽

Qidong Cai ◽

Pengfei Zhang ◽

Xiong Peng ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Clinical Application ◽

Risk Group ◽

High Risk Group ◽

Immune Microenvironment ◽

Tumor Mutation Burden ◽

Immune Signature ◽

Immune Infiltration ◽

Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

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