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

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

Cancer Science ◽

10.1111/j.1349-7006.2011.02197.x ◽

2012 ◽

Vol 103 (4) ◽

pp. 731-738 ◽

Cited By ~ 26

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

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

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezaa138 ◽

2020 ◽

Vol 58 (5) ◽

pp. 1010-1018 ◽

Cited By ~ 1

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.

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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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