scholarly journals Poor prognosis of stage I lung adenocarcinoma patients determined by elevated expression over pre/minimally invasive status of COL11A1 and THBS2 in the focal adhesion pathway

2022 ◽  
Author(s):  
Leming Shi ◽  
Jun Shang ◽  
Yue Zhao ◽  
He Jiang ◽  
Jingcheng Yang ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Lung Adenocarcinoma ◽  
Focal Adhesion ◽  
Poor Prognosis ◽  
Stage I ◽  
Molecular Characteristics ◽  
Cancer Associated Fibroblast ◽  
Post Surgery ◽  
Elevated Expression ◽  
Invasive Status

Abstract Patients with adenocarcinomas in situ (AIS) and minimally invasive (MIA) lung adenocarcinoma (LUAD) are curable by surgery, whereas 20% stage I patients die within five years post-operative. We hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. Focal adhesion (FA) was identified as the only pathway significantly perturbed at both genomic and transcriptomic levels by comparing 98 AIS/MIA and 99 LUAD. Then, two FA genes (COL11A1 and THBS2) were found strongly upregulated from AIS/MIA to stage I while steadily expressed from normal to AIS/MIA. Furthermore, unsupervised clustering separated stage I patients into two molecularly and prognostically distinct subtypes (S1 and S2) based on COL11A1 and THBS2 expressions (FA2). Subtype S1 resembled AIS/MIA, whereas S2 exhibited more somatic alterations and activated cancer-associated fibroblast. The simple knowledge-driven model was validated with 12 external datasets, showing potential in identifying high-risk stage I patients for more intensive post-surgery treatment.

scholarly journals Poor prognosis of stage I lung adenocarcinoma patients determined by elevated expression over pre/minimally invasive status of COL11A1 and THBS2 in the focal adhesion pathway

2021 ◽  
Author(s):  
Jun Shang ◽  
Yue Zhao ◽  
He Jiang ◽  
Jingcheng Yang ◽  
Naixin Zhang ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Lung Adenocarcinoma ◽  
Focal Adhesion ◽  
Poor Prognosis ◽  
Stage I ◽  
Molecular Characteristics ◽  
Data Sets ◽  
External Data ◽  
Post Surgery ◽  
Elevated Expression

Around 20% stage I lung adenocarcinoma (LUAD) patients die within five years after surgery, and efforts for developing gene-expression based models for risk-tailored post-surgery treatment are largely unsatisfactory due to overfitting-related lack of validation and extrapolation. Because patients with adenocarcinomas in situ (AIS) and minimally invasive (MIA) LUAD are completely curable by surgical resection, we hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. We first found focal adhesion (FA) as the only pathway significantly perturbed at both genomic and transcriptomic levels by comparing 98 AIS/MIA and 99 invasive LUAD patients. Then, we identified two FA pathway genes (COL11A1 and THBS2) strongly upregulated from AIS/MIA to stage I while expressed steadily from normal to AIS/MIA. Furthermore, unsupervised clustering separated stage I patients into two molecularly and prognostically distinct subtypes (S1 and S2) based solely on the expression levels of COL11A1 and THBS2 (FA2). Subtype S1 looked like AIS/MIA, whereas S2 exhibited more somatic alterations, elevated expression of COL11A1 and THBS2, and more activated cancer-associated fibroblast (CAF). The prognostic performance of the knowledge-driven and overfitting-resistant FA2 model was validated with 12 external data sets and may help reliably identify high-risk stage I patients for more intensive post-surgery treatment.

scholarly journals MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly

2021 ◽  
Author(s):  
Yan Zhong ◽  
Ting Long ◽  
Chuan-Sha Gu ◽  
Jing-Yi Tang ◽  
Ling-Fang Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Focal Adhesion ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Integrin Β1 ◽  
Independent Manner ◽  
Interacting Protein ◽  
Tumour Metastasis ◽  
Elevated Expression ◽  
Dependent Polarization

AbstractTumour metastasis is a major reason accounting for the poor prognosis of colorectal cancer (CRC), and the discovery of targets in the primary tumours that can predict the risk of CRC metastasis is now urgently needed. In this study, we identified autophagy-related protein 9B (ATG9B) as a key potential target gene for CRC metastasis. High expression of ATG9B in tumour significantly increased the risk of metastasis and poor prognosis of CRC. Mechanistically, we further find that ATG9B promoted CRC invasion mainly through autophagy-independent manner. MYH9 is the pivotal interacting protein for ATG9B functioning, which directly binds to cytoplasmic peptide segments aa368–411 of ATG9B by its head domain. Furthermore, the combination of ATG9B and MYH9 enhance the stability of each other by decreasing their binding to E3 ubiquitin ligase STUB1, therefore preventing them from ubiquitin-mediated degradation, which further amplified the effect of ATG9B and MYH9 in CRC cells. During CRC cell invasion, ATG9B is transported to the cell edge with the assistance of MYH9 and accelerates focal adhesion (FA) assembly through mediating the interaction of endocytosed integrin β1 and Talin-1, which facilitated to integrin β1 activation. Clinically, upregulated expression of ATG9B in human CRC tissue is always accompanied with highly elevated expression of MYH9 and associated with advanced CRC stage and poor prognosis. Taken together, this study highlighted the important role of ATG9B in CRC metastasis by promoting focal adhesion assembly, and ATG9B together with MYH9 can provide a pair of potential therapeutic targets for preventing CRC progression.

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

2001 ◽  
Vol 12 (8) ◽  
pp. 1121-1125 ◽  
Author(s):  
Y. Saijo ◽  
G. Sato ◽  
K. Usui ◽  
M. Sato ◽  
M. Sagawa ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Nucleolar Protein ◽  
Stage I

scholarly journals Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yingyan Wang ◽  
Wen Lan ◽  
Mingxin Xu ◽  
Jing Song ◽  
Jun Mao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
Stromal Cell Derived Factor ◽  
Targeted Approach

AbstractCancer-associated fibroblasts (CAFs) contribute to tumour epithelial-mesenchymal transition (EMT) via interaction with cancer cells. However, the molecular mechanisms underlying tumour-promoting EMT of CAFs in lung adenocarcinoma (ADC) remain unclear. Here, we observed that CAFs isolated from lung ADC promoted EMT via production of stromal cell-derived factor-1 (SDF-1) in conditioned medium (CM). CAF-derived SDF-1 enhanced invasiveness and EMT by upregulating CXCR4, β-catenin, and PPARδ, while downregulating these proteins reversed the effect. Furthermore, RNAi-mediated CXCR4 knockdown suppressed β-catenin and PPARδ expression, while β-catenin inhibition effectively downregulated PPARδ without affecting CXCR4; however, treatment with a PPARδ inhibitor did not inhibit CXCR4 or β-catenin expression. Additionally, pairwise analysis revealed that high expression of CXCR4, β-catenin, and PPARδ correlated positively with 75 human lung adenocarcinoma tissues, which was predictive of poor prognosis. Thus, targeting the CAF-derived, SDF-1-mediated CXCR4 β-catenin/ PPARδ cascade may serve as an effective targeted approach for lung cancer treatment.

Elevated Expression of LYPD3 Is Associated with Lung Adenocarcinoma Carcinogenesis and Poor Prognosis

2020 ◽  
Vol 39 (4) ◽  
pp. 522-532 ◽  
Author(s):  
Ping Hu ◽  
Ying Huang ◽  
Yuanyuan Gao ◽  
Hui Yan ◽  
Xiaoge Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Elevated Expression

scholarly journals Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma

2012 ◽  
Vol 103 (4) ◽  
pp. 731-738 ◽  
Author(s):  
Di-Cing Wei ◽  
Yi-Chen Yeh ◽  
Jung-Jyh Hung ◽  
Teh-Ying Chou ◽  
Yu-Chung Wu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Stage I ◽  
Lak Cell

scholarly journals Impact of the micropapillary component on the timing of recurrence in patients with resected lung adenocarcinoma

2020 ◽  
Vol 58 (5) ◽  
pp. 1010-1018 ◽  
Author(s):  
Katsuya Watanabe ◽  
Kentaro Sakamaki ◽  
Hiroyuki Ito ◽  
Tomoyuki Yokose ◽  
Kozo Yamada ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Postoperative Recurrence ◽  
Early Recurrence ◽  
Stage I ◽  
Hazard Curves ◽  
And Gender ◽  
The Impact

Abstract OBJECTIVES A micropapillary (MIP) component is reported to be associated with a poor prognosis in patients with completely resected lung adenocarcinoma. The purpose of this study was to investigate the impact of an MIP component on the timing of postoperative recurrence using hazard curves. METHODS A total of 1289 patients with lung adenocarcinoma who underwent complete pulmonary resection from 2008 to 2015 were studied. Hazard curves representing the changes in hazard over time were evaluated. RESULTS The hazard curve displayed an initial wide, high peak within 1 year after surgery in patients with an MIP component, whereas some gentle peaks around the second year were noted in patients without an MIP component. The presence of an MIP component was associated with a worse recurrence-free survival and an early recurrence in stage I patients but not in advanced-stage patients. In multivariable Cox regression, the presence of an MIP component and lymph node metastasis, pleural invasion and gender were associated with a poor prognosis. CONCLUSIONS Patients with an MIP component retained a high risk of early recurrence after surgery, and the risk for recurrence persisted over the long term. Even after complete resection in stage I lung adenocarcinoma patients, an MIP component remains correlated with a poor prognosis.

1495: Elevated Expression of Tumor-Associated Macrophages is Associated with Poor Prognosis of Human Prostate Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 483-483
Author(s):  
Hitoshi Takayama ◽  
Norio Nonomura ◽  
Daizo Oka ◽  
Masahiro Shiba ◽  
Yasuyuki Arai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Poor Prognosis ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Tumor Associated Macrophages ◽  
Elevated Expression
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