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

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.

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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

10.21203/rs.3.rs-1218087/v1 ◽

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.

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

The Journal of Urology ◽

10.1016/s0022-5347(18)33699-1 ◽

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

Cell Death and Differentiation ◽

10.1038/s41418-021-00813-z ◽

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.

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