Development and Validation of a Novel Signature to Predict Overall Survival in “Driver Gene–negative” Lung Adenocarcinoma (LUAD): Results of a Multicenter Study

Cui, Yongmei; Fang, Wenfeng; Li, Chaofeng; Tang, Kejing; Zhang, Jian; Lei, Yiyan; He, Weiling; Peng, Sui; Kuang, Ming; Zhang, Hui; Chen, Lili; Xu, Di; Tang, Cuilan; Zhang, Wenhui; Zhu, Yuxin; Jiang, Wenting; Jiang, Neng; Sun, Yu; Chen, Yangshan; Wang, Han; Lai, Yingrong; Li, Shuhua; He, Qi; Zhou, Jianwen; Zhang, Yang; Lin, Millicent; Chen, Honglei; Zhou, Chengzhi; Wang, Chunlin; Wang, Jianhong; Zou, Xuenong; wang, Lian-tang; Ke, Zunfu

doi:10.1158/1078-0432.ccr-18-2545

Cited by 39 publications

(41 citation statements)

References 44 publications

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“…Representative paraffin-embedded tissues were arrayed with a tissue-arraying instrument with 2.0-mm diameter core and were sectioned (4 um) for further analysis. CTHRC1 (Abcam, Cambridge, UK) was used in a 1:100 dilution [29, 30], VEGF (ZSGB-Bio, Beijing, China) and CD34 (ZSGB-Bio, Beijing, China) was used in ready to use dilution [31]. Samples were incubated with antibodies against CTHRC1 (Abcam, Cambridge, UK), VEGF (ZSGB-Bio, Beijing, China) and CD34 (ZSGB-Bio, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

et al. 2019

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BackgroundThis study aimed to investigate the prognostic value of the potential biomarker collagen triple helix repeat containing 1 (CTHRC1) in lung adenocarcinoma (LUAD) patients.MethodsA total of 210 LUAD patients diagnosed between 2003 and 2016 in the Department of Pathology of the First Affiliated Hospital of Sun Yat-sen University were included in this study. The expression of CTHRC1 and vascular endothelial growth factor (VEGF), and microvessel density (MVD, determined by CD34 immunostaining) were evaluated by immunohistochemistry in LUAD tissues. The association between the expression of these proteins and clinicopathological features or clinical outcomes was analyzed.ResultsHere, we confirmed that CTHRC1 expression was associated with prognosis and can serve as a significant predictor for overall survival (OS) and progression-free survival (PFS) in LUAD. Additionally, we observed that CTHRC1 expression was positively associated with tumor angiogenesis markers, such as VEGF expression (P < 0.001) and MVD (P < 0.01). Then, we performed gene set enrichment analysis (GESA) and cell experiments to confirm that enhanced CTHRC1 expression can promote VEGF levels. Based on and cox regression analysis, a predictive model that included CTHRC1, VEGF and MVD was constructed and confirmed as a more accurate independent predictor for OS (P = 0.001) and PFS (P < 0.001) in LUAD than other parameters.ConclusionsThese results demonstrated that high CTHRC1 expression may be closely related to tumor angiogenesis and poor prognosis in LUAD. The predictive model based on the CTHRC1 level and tumor angiogenesis markers can be used to predict LUAD patient prognosis more accurately.

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Section: Methodsmentioning

confidence: 99%

High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

et al. 2019

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“…account for 50%-60% of patients with advanced NSCLC, and for these patients it is particularly important to adopt accurate evidence-based diagnosis methods and treatment strategies (59). Before the advent of immunotherapy, the standard treatment for Stage IV NSCLC was chemotherapy with platinum (60).…”

Section: Figurementioning

confidence: 99%

Consistency of recommendations for the diagnosis and treatment of non-small cell lung cancer: a systematic review

Zhang¹,

Yang²,

Ma³

et al. 2021

Transl Lung Cancer Res

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Background: To systematically assess the consistency of recommendations regarding diagnosis and treatment of non-small cell lung cancer (NSCLC) in clinical practice guidelines (CPGs).Methods: We systematically searched relevant literature databases and websites to identify CPGs related to NSCLC. We extracted the general characteristics of the included guidelines and their recommendations and descriptively compared and analyzed the consistency of recommendations across the guidelines.Results: A total of 28 NSCLC guidelines were retrieved. The recommendations covered mainly diagnosis and treatment. The recommendations in the guidelines differed substantially in various topics, such as the application of positron emission tomography (PET) and the classification of stage III. Fourteen guidelines divided stage III into two types: operable and inoperable; and the remaining 14 guidelines into three sub-stages IIIA, IIIB and IIIC. Recommendations regarding the treatment in stage III were relatively inconsistent. In driver gene (EGFR, ALK, ROS1) positive patients, targeted therapy was the most common recommendation for first-line treatment, but recommendations regarding second-line treatment varied according to the site of the mutation. In driver gene negative patients, immunotherapy was the most frequently recommended option as both first-and second-line treatment, followed by chemotherapy.Discussion: A number of countries are devoting themselves to develop NSCLC guidelines and the process of updating guidelines is accelerating, yet recommendations between guidelines are not consistent. We adopted a systematic review method to systematically search and analyze the NSCLC guidelines worldwide.We objectively reviewed the differences in recommendations for NSCLC diagnosis and treatment between the guidelines. Inconsistency of recommendations across guidelines can result from multiple potential reasons. Such as, the guidelines developed time, different countries and regions and many more. Poor consistency across CPGs can confuse the guideline users, and we therefore advocate paying more attention to examining the controversies and updating guidelines timely to improve the consistency among CPGs.Our study had also several limitations, we limited the search to CPGs published in Chinese or English, the interpretation of recommendations is inherently subjective, we did not evaluate the details of the clinical content of the CPG recommendations. Our research presents the current status of NSCLC guidelines worldwide and give the opportunity to pay more attention to the existing gaps. Further investigations should 2 Zhang et al. Consistency of NSCLC guidelines recommendations

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“…For statistical evaluation, tissues were scored as 0 (nonstaining); 1, 1-25%; 2, 26-50%; 3, 51-75%; 4, 76-100% (positive staining). BCAT1 protein expression was evaluated as negative (0), weak positive (1, 2), positive (3,4) according to the staining positive rate score. The total histological score was de ned as the product of "staining intensity score" and "staining positive rate score", and 0-5 indicated BCAT1 low expression while 6-12 indicated BCAT1 high expression.…”

Section: Immunohistochemistry (Ihc) and Evaluationmentioning

confidence: 99%

“…NSCLC mainly includes LUAD and squamous cell carcinoma (SCC) 2 . Among NSCLC cases, LUAD accounts for about 60% and remains a major cause of cancer-related mortality worldwide 3,4 . In recent years, increasing researches on the pathobiology and progression of lung cancer have been performed and many genes have been identi ed as potential drivers and targets for therapy [5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

BCAT1 Promotes Lung Adenocarcinoma Progression Through Enhanced Mitochondrial Respiration and NF-κB Pathway Activation

Zhao

et al. 2021

Preprint

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BCAT1 is up-regulated and acts as an oncogenic factor in many types of cancers, but its role in lung adenocarcinoma (LUAD) development is not clearly understood. Here we found BCAT1 protein level was up-regulated in tumor tissues, which was positively associated with TNM stage and local lymph node metastasis of LUAD patients. BCAT1 knockdown inhibited cell growth and mobility while BCAT1 overexpression promoted LUAD development both in vitro and in vivo. BCAAs metabolism and mitochondrial respiration were enhanced in BCAT1 overexpression cells, which were more sensitive to Leucine and Isoleucine supplements, compared to control cells. Moreover, RNA sequencing analysis suggested that differentially expressed genes (DEGs) in BCAT1 overexpression LUAD cells were enriched in metabolism, signal transduction, and immune response processes, and BCAT1 overexpression decreased NFKBIB mRNA level that induced NF-κB pathway activation in LUAD cells. As an inhibitor of NF-κB pathway, ammonium pyrrolidinedithiocarbamate (PDTC) treatment predominately counteracted the effect of NF-κB pathway activation and inhibited LUAD cells proliferation and migration, especially cells with BCAT1 overexpression. Taken together, our findings point a key role for BCAT1 in promoting LUAD development through metabolic reprogramming and NF-κB pathway activation, which provides promising molecular biomarker and therapeutic targets for LUAD diagnosis and treatment.

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Development and Validation of a Novel Signature to Predict Overall Survival in “Driver Gene–negative” Lung Adenocarcinoma (LUAD): Results of a Multicenter Study

Cited by 39 publications

References 44 publications

High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

High CTHRC1 expression may be closely associated with angiogenesis and indicates poor prognosis in lung adenocarcinoma patients

Consistency of recommendations for the diagnosis and treatment of non-small cell lung cancer: a systematic review

BCAT1 Promotes Lung Adenocarcinoma Progression Through Enhanced Mitochondrial Respiration and NF-κB Pathway Activation

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