Dataset Information

The prognostic effect of TTF-1 expression in the Chinese population of patients with advanced lung adenocarcinomas.

ABSTRACT: Background:Thyroid transcription factor 1 (TTF-1), which is usually expressed by lung adenocarcinomas and small cell carcinomas, is usually used to distinguish adenocarcinoma and small cell carcinoma from cells of another type of lung cancer. We examined the association between TTF-1 expression and overall survival between patients with stage IV pulmonary adenocarcinoma to investigate the role of TTF-1 as a predictive and/or prognostic tumor marker in patients with advanced lung adenocarcinomas. Methods:Analysis of the clinicopathologic features, treatment regimens, and overall survival of 209 lung adenocarcinoma patients who had been detected for TTF-1 expression and received consecutive treatments in the Affiliated Hospital of Qingdao University. Results:TTF-1 expression was positive in 166 (79%) and negative in 43 (21%) patients who were reviewed. Moreover, there was no significant difference between the clinicopathologic features of TTF-1 positive and TTF-1 negative tumors. In the multivariable review, the overall survival of TTF-1 positive tumor patients was significantly longer than that of TTF-1 negative tumor patients [22.7 vs. 11.8 months (P<0.0001)], increasing the prognostic effect of Karnofsky performance status and receiving first-line chemotherapy or targeted therapy. Positive TTF-1 and negative TTF-1 patients receiving pemetrexed-based chemotherapy improved the duration of treatment compared to those receiving non-pemetrexed chemotherapy. Conclusions:TTF-1 expression was associated with an improved survival in patients with advanced lung adenocarcinomas. Both patients, either TTF-1 positive or negative, could benefit from the first-line chemotherapy or pemetrexed treatment option. However, as discovered by our investigation, TTF-1 cannot forecast a portion of the lung adenocarcinomas that had a selective sensitivity to pemetrexed.

SUBMITTER: Li X

PROVIDER: S-EPMC7082290 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The prognostic effect of TTF-1 expression in the Chinese population of patients with advanced lung adenocarcinomas.

Li Xueying X Yin Ling L Zhao Yamei Y He Man M Qi Qi Q Sun Yang Y Li Hongmei H Evison Matthew M

Translational lung cancer research 20200201 1

<h4>Background</h4>Thyroid transcription factor 1 (TTF-1), which is usually expressed by lung adenocarcinomas and small cell carcinomas, is usually used to distinguish adenocarcinoma and small cell carcinoma from cells of another type of lung cancer. We examined the association between TTF-1 expression and overall survival between patients with stage IV pulmonary adenocarcinoma to investigate the role of TTF-1 as a predictive and/or prognostic tumor marker in patients with advanced lung adenocar ...[more]

PMID: 32206556

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Project description:BackgroundWe aimed to assess if quantitative radiomic features can predict programmed death ligand 1 (PD-L1) expression in advanced stage lung adenocarcinoma.MethodsThis retrospective study included 153 patients who had advanced stage (>IIIA by TNM classification) lung adenocarcinoma with pretreatment thin section computed tomography (CT) images and PD-L1 expression test results in their pathology reports. Clinicopathological data were collected from electronic medical records. Visual analysis and radiomic feature extraction of the tumor from pretreatment CT were performed. We constructed two models for multivariate logistic regression analysis (one based on clinical variables, and the other based on a combination of clinical variables and radiomic features), and compared c-statistics of the receiver operating characteristic curves of each model to identify the model with the higher predictability.ResultsAmong 153 patients, 53 patients were classified as PD-L1 positive and 100 patients as PD-L1 negative. There was no significant difference in clinical characteristics or imaging findings on visual analysis between the two groups (P > 0.05 for all). Rad-score by radiomic analysis was higher in the PD-L1 positive group than in the PD-L1 negative group with a statistical significance (-0.378 ± 1.537 vs. -1.171 ± 0.822, P = 0.0008). A prediction model that uses clinical variables and CT radiomic features showed higher performance compared to a prediction model that uses clinical variables only (c-statistic = 0.646 vs. 0.550, P = 0.0299).ConclusionsQuantitative CT radiomic features can predict PD-L1 expression in advanced stage lung adenocarcinoma. A prediction model composed of clinical variables and CT radiomic features may facilitate noninvasive assessment of PD-L1 expression.Key pointsSignificant findings of the study Quantitative CT radiomic features can help predict PD-L1 expression, whereas none of the qualitative imaging findings is associated with PD-L1 positivity. What this study adds A prediction model composed of clinical variables and CT radiomic features may facilitate noninvasive assessment of PD-L1 expression.

Project description:The major driver mutations of lung cancer, EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we carried out whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2-1/TTF-1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2-1/TTF-1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1/TTF-1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2-1)/thyroid transcription factor 1 (TTF-1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1/TTF-1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF-1-postive/hepatocyte nuclear factor 4-? (HNF4-?)-negative and TTF-1-negative/HNF4-?-positive groups. NKX2-1/TTF-1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2-1/TTF-1 gene body was highly methylated in NKX2-1/TTF-1-negative cases, including those without the NKX2-1/TTF-1 mutations. The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas.

Dataset Information

The prognostic effect of TTF-1 expression in the Chinese population of patients with advanced lung adenocarcinomas.

Publications

The prognostic effect of TTF-1 expression in the Chinese population of patients with advanced lung adenocarcinomas.

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