Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical rol...Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.展开更多
Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinician...Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinicians and pathologists still have an insufficient understanding of this disease.This study aims to characterize the morphological,immunohistochemical,and genetic features of BA and its variants,and to determine whether BA can progress to a malignancy.Methods Among these 33 cases,21 were histologically characterized by double-layered tumors with continuous basal cell layers.Six patients exhibited a partial classic bilayer,transitioning from a bilayer to a monolayer in certain lesion areas(mixed-type BAs).Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA.Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.Results All the cellular components exhibited a relatively mild morphology.Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6.Thyroid transcription factor 1 was expressed in the double-cell layer,which consists of ciliated columnar epithelial cells,basal cells,nonciliated columnar epithelial cells,and cuboidal epithelial cells.The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs(43%),2 of 6 mixed-type BAs(33%),and 3 of 6 monolayered BA-like lesions(50%).Genetically,monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures,whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.Conclusion These findings underscore the histopathological and genetic characteristics of BA and its variants,suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma.In the future,more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.展开更多
Papillary thyroid carcinoma （PTC） is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was ident...Papillary thyroid carcinoma （PTC） is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 （located at the 14q13.3 locus）, which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained （C vs. T, P= 0.027, OR= 1.264, 95% CI = 1.026-1.557; and C/C-C/T vs. T/T, P= 0.034, OR= 1.474, 95% CI = 1.028-2.112）. Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 （adjusted P = 0.062） between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction （P= 0.029; OR = 2.578, 95% CI=1.104-6.023） between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.展开更多
Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based o...Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 diabetes.However,significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids(FFAs)into the blood circulation,which leads to a marked reduction in membrane flexibility.These data favor a FFA-glucose-insulin axis.The authors are invited to extend their study with the introduction of the saturation index(number of carbon-carbon double bonds per 100 fatty-acyl chains),as observed in erythrocytes.展开更多
基金supported by the Zhejiang Provincial Natural Science Foundation of China (No. LQ12H01001)the Zhejiang Provincial Medicine & Health Scientific Foundation of China (No. 2012KYA143)
文摘Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.
基金supported by Xi'an Jiaotong University Medical Development Fund(No.XJYG2025-SFJJ011)Natural Science Foundation of Inner Mongolia Autonomous Region(No.2023LHMS08027).
文摘Objective Bronchiolar adenoma(BA)is a peripheral pulmonary neoplasm characterized by a bilayered cell structure com-posed of basal cells and luminal cells.Owing to its low incidence and limited research data,clinicians and pathologists still have an insufficient understanding of this disease.This study aims to characterize the morphological,immunohistochemical,and genetic features of BA and its variants,and to determine whether BA can progress to a malignancy.Methods Among these 33 cases,21 were histologically characterized by double-layered tumors with continuous basal cell layers.Six patients exhibited a partial classic bilayer,transitioning from a bilayer to a monolayer in certain lesion areas(mixed-type BAs).Six other BA-like tumors with monolayered components might represent the early stage of malignant transformation of BA.Next-generation sequencing analysis was conducted on 33 cases to elucidate the genetic spectrum.Results All the cellular components exhibited a relatively mild morphology.Immunohistochemical analysis revealed that basal cells coexpressed p40 and cytokeratin 5/6.Thyroid transcription factor 1 was expressed in the double-cell layer,which consists of ciliated columnar epithelial cells,basal cells,nonciliated columnar epithelial cells,and cuboidal epithelial cells.The pan-cancer gene panel was used to observe driver alterations in 9 of 21 classic bilayered BAs(43%),2 of 6 mixed-type BAs(33%),and 3 of 6 monolayered BA-like lesions(50%).Genetically,monolayered BA-like lesions shared some alterations with classic BAs in mutational signatures,whereas NKX2-1 mutations were enriched only in monolayered BA-like lesions.Conclusion These findings underscore the histopathological and genetic characteristics of BA and its variants,suggesting that monolayered BA-like lesions have the potential to develop into lung adenocarcinoma.In the future,more cases should be recruited to further explore the malignant transformation of this specific entity via the multidimensional spectrum.
文摘Papillary thyroid carcinoma （PTC） is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 （located at the 14q13.3 locus）, which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained （C vs. T, P= 0.027, OR= 1.264, 95% CI = 1.026-1.557; and C/C-C/T vs. T/T, P= 0.034, OR= 1.474, 95% CI = 1.028-2.112）. Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 （adjusted P = 0.062） between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction （P= 0.029; OR = 2.578, 95% CI=1.104-6.023） between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.
文摘Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels.This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 diabetes.However,significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids(FFAs)into the blood circulation,which leads to a marked reduction in membrane flexibility.These data favor a FFA-glucose-insulin axis.The authors are invited to extend their study with the introduction of the saturation index(number of carbon-carbon double bonds per 100 fatty-acyl chains),as observed in erythrocytes.
