scholarly journals TP53 Status, Patient Sex, and the Immune Response as Determinants of Lung Cancer Patient Survival

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1535 ◽  
Author(s):  
Donald Freudenstein ◽  
Cassandra Litchfield ◽  
Franco Caramia ◽  
Gavin Wright ◽  
Benjamin J. Solomon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Gene Mutations ◽  
Lung Squamous Cell Carcinoma ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
The Cancer Genome Atlas ◽  
Immune Signatures ◽  
Tp53 Gene Mutations

Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-γ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-β) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter: PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures.

scholarly journals LRH1 Acts as an Oncogenic Driver in Human Osteosarcoma and Pan-Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Song ◽  
Weiwei An ◽  
Hongmei Wang ◽  
Yuanren Gao ◽  
Jihua Han ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Lung Squamous Cell Carcinoma ◽  
Metastatic Potential ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Childhood And Adolescence

Osteosarcoma (OS) that mainly occurs during childhood and adolescence is a devastating disease with poor prognosis presented by extreme metastases. Recent studies have revealed that liver receptor homolog 1 (LRH-1) plays a vital role in the metastasis of several human cancers, but its role is unknown in the metastasis of OS. In this study, Gene Ontology (GO) enrichment analyses based on high-throughput RNA-seq data revealed that LRH-1 acted a pivotal part in the positive regulation of cell migration, motility, and angiogenesis. Consistently, LRH-1 knockdown inhibited the migration of human OS cells, which was concurrent with the downregulation of mesenchymal markers and the upregulation of epithelial markers. In addition, short hairpin RNAs (shRNAs) targeting LRH-1 inactivated transforming growth factor beta (TGF-β) signaling pathway. LRH-1 knockdown inhibited human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. Vascular endothelial growth factor A (VEGFA) expression was also downregulated after LRH-1 knockdown. Immunohistochemistry (IHC) revealed that the expression of LRH-1 protein was significantly higher in tumor tissues than in normal bone tissues. We found that high LRH-1 expression was associated with poor differentiation and advanced TNM stage in OS patients using IHC. Based on The Cancer Genome Atlas (TCGA) database, high LRH-1 expression predicts poor survival in lung squamous cell carcinoma (LUSC), kidney renal papillary cell carcinoma (KIRP), and pancreatic adenocarcinoma (PAAD). The downregulation of LRH-1 significantly hindered the migration and motility of LUSC cells. Using multi-omic bioinformatics, the positive correlation between LRH-1- and EMT-related genes was found across these three cancer types. GO analysis indicated that LRH-1 played a vital role in “blood vessel morphogenesis” or “vasculogenesis” in KIRP. Our results indicated that LRH-1 plays a tumor-promoting role in human OS, could predict the early metastatic potential, and may serve as a potential target for cancer therapy.

Analysis of TP53 Gene Mutations in the Korean Patients with Lung Cancer

2011 ◽  
Vol 1 (4) ◽  
pp. 202
Author(s):  
Sang Bong Jung ◽  
Hee Kyung Chang ◽  
Seok Cheol Choi ◽  
Kyeong-Cheol Shin ◽  
Kwan-Ho Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Korean Patients ◽  
Tp53 Gene Mutations

scholarly journals Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200633 ◽  
Author(s):  
Zahra Fathi ◽  
Seyed Ali Javad Mousavi ◽  
Raheleh Roudi ◽  
Farideh Ghazi
Keyword(s):  
Lung Cancer ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Iranian Patients ◽  
Tp53 Gene Mutations

scholarly journals The lack of correlation between TP53 mutations and gastric cancer: A report from a province of Iran

Genetika ◽  
2017 ◽  
Vol 49 (1) ◽  
pp. 235-246 ◽  
Author(s):  
Javad Saffari-Chaleshtori ◽  
Mohammad-Amin Tabatabaiefar ◽  
Payam Ghasemi-Dehkordi ◽  
Effat Farokhi ◽  
Mohammad-Taghi Moradi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Genetic Alterations ◽  
Pcr Rflp ◽  
Tp53 Tumor Suppressor Gene ◽  
Broad Role ◽  
Tp53 Gene Mutations

Gastric cancer ranks second cause of cancer death worldwide after lung cancer. Its etiology is heterogeneous and genetic factors including protooncogenes and tumor suppressor genes always contribute to the progression of cancer. The TP53 tumor suppressor gene has a broad role in genomic stability and DNA repair. The aim of this study was to determine the TP53 gene mutations in gastric cancer specimens in Chaharmahal Va Bakhtiari province of Iran. In this descriptive-lab based study, we investigated the promoter and exons of TP53 gene mutations in 38 paraffin-embedded gastric cancer specimens. DNA was extracted following a standard phenol-chloroform protocol. The TP53 gene mutations were determined using PCR-SSCP & PCR-RFLP procedures. The present study revealed no TP53 gene mutation in the promoter and exons in the gastric cancer subjects studied. While TP53 gene mutations have been reported as the most frequent genetic alterations and are found in about 50% of the human malignancies, no mutation was detected in this study. This may be due to mutations in other related genes in the same pathway or epigenetic factors.

TP53 gene mutations of lung cancer patients in upper northern Thailand and environmental risk factors

2008 ◽  
Vol 185 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Kanokkan Bumroongkit ◽  
Bruce Rannala ◽  
Patrinee Traisathit ◽  
Metawee Srikummool ◽  
Yannawan Wongchai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Cancer Patients ◽  
Environmental Risk ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Environmental Risk Factors ◽  
Northern Thailand ◽  
Lung Cancer Patients ◽  
Tp53 Gene Mutations

1068: TP53 Gene Mutations as a Prognostic Marker for PSA Progression in Early Stage Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 282-282
Author(s):  
Markus D. Sachs ◽  
Horst Schlechte ◽  
Katrin Schiemenz ◽  
Severin V. Lenk ◽  
Dietmar Schnorr ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Marker ◽  
Early Stage ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Psa Progression ◽  
Tp53 Gene Mutations

scholarly journals Downregulation of NKG2DLs by TGF-β in human lung cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Young Shin Lee ◽  
Hojung Choi ◽  
Hae-Ryung Cho ◽  
Woo-Chang Son ◽  
You-Soo Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Nk Cell ◽  
Surface Proteins ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Altered Expression ◽  
Inhibitory Molecules

Abstract Background Transforming growth factor beta (TGF-β) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-β and a TGF-β inhibitor, Galunisertib (LY2157299). Results TGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-β or Galunisertib. Conclusions Therefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

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