Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.
Adenocarcinoma/pathology* ; Adenocarcinoma of Lung/pathology* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Colonic Neoplasms/pathology* ; Diagnosis, Differential ; Humans ; Lung Neoplasms/genetics* ; Male ; Middle Aged

BACKGROUND: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an innovative technique for diagnosis and staging of lung cancer. But whether the procedure can provide enough tissue for the detection of gene mutations is still to be defined. Here we evaluated the efficacy of lung cancer diagnosis and gene analysis using samples obtain via EBUS-TBNA. METHODS: Patients with suspected lung cancer and mediastinal lesions were referred for EBUS-TBNA. Diagnosis and sub-classifications were made by pathologists. Samples with non-squamous non small cell lung cancer sub type were tested for the EGFR and/or ALK mutations. RESULTS: A total of 377 patients were included in this study. The median needle passes were 2.07. Lung cancer was diagnosed in 213 patients. The diagnosis accuracy for malignancy was 92%. Epidermal growth factor receptor (EGFR) mutations, anaplasticlymphoma kinase (ALK) fusion genes and double genes analysis were successfully preformed in 84 (90%), 105 (95%) and 79 (90%) patients. The number of needle passes and the diameters of lymph node were not associated with the efficacy of gene testing in univariate analysis. However, samples of adenocarcinoma sub type showed a tendency associated with higher genotyping efficacy. CONCLUSIONS Tissue samples obtained through EBUS-TBNA are sufficient for pathological diagnosis and genetic analysis of lung cancer. The pathology type of sample affected genotyping efficacy.
Adult ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; pathology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Feasibility Studies ; Female ; Genotyping Techniques ; Humans ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; Male

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

Lung cancer is one of the most important malignant tumors in the world. The morbidity and mortality rank the first in all kinds of cancer. Long non-coding RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays an important role in the epigenetic regulation, cell cycle regulation, the regulation of cell differentiation, and many other life activities. The studies indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC) tissue and blood circulation is associated with the occurrence and development of cancer. The lncRNAs play an significant role in proliferation, differentiation, migration and apoptosis of the tumor cells. Explore the potential mechanism between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy and improve prognosis. Therefore, the study aims to demonstrate the latest studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for the prevention of NSCLC.
Carcinogenesis ; genetics ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Molecular Targeted Therapy ; RNA, Long Noncoding ; genetics

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma ; diagnosis ; genetics ; mortality ; pathology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; mortality ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; mortality ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Lung Neoplasms ; diagnosis ; genetics ; mortality ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Analysis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Non-Small-Cell Lung/blood/diagnosis/*drug therapy/genetics ; Cell Line, Tumor ; Cisplatin/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/blood/diagnosis/*drug therapy/genetics ; Male ; Mice ; Mice, Nude ; MicroRNAs/blood/*genetics ; Middle Aged ; Prognosis ; Survival Analysis ; Treatment Outcome

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Animals ; Antineoplastic Agents/*therapeutic use ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Non-Small-Cell Lung/blood/diagnosis/*drug therapy/genetics ; Cell Line, Tumor ; Cisplatin/*therapeutic use ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung/*drug effects/metabolism/pathology ; Lung Neoplasms/blood/diagnosis/*drug therapy/genetics ; Male ; Mice ; Mice, Nude ; MicroRNAs/blood/*genetics ; Middle Aged ; Prognosis ; Survival Analysis ; Treatment Outcome

No abstract available.
Antineoplastic Agents/therapeutic use ; Ascitic Fluid/*cytology ; Carcinoma, Non-Small-Cell Lung/*diagnosis/drug therapy/pathology ; Humans ; Lung Neoplasms/*diagnosis/drug therapy/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/genetics ; Small Cell Lung Carcinoma/*diagnosis/pathology ; Tomography, X-Ray Computed

Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo establish a diagnostic model of protein fingerprint pattern in the cerebrospinal fluid (CSF) for non-small-cell lung cancer (NSCLC) patients with brain metastases.

METHODSThe CSF samples were obtained from 29 NSCLC patients with brain metastasis, 23 non-tumor patients and 10 early-stage NSCLC patients without brain metastases for analysis of the protein expression profiles using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data were then analyzed by Biomarker Wizard software, and the tree analysis patterns were generated using the decision-tree model in Biomarker Patterns software. The diagnostic model was tested for its clinical application.

RESULTSFive protein peaks were identified showing differential expression between patients with brain metastases and those without brain metastases. Combination of the 3 protein peaks (m/z: 8698.00, 1215.32 and 1245.70) could discriminate these two samples with a sensitivity of 100.00% (29/29) and a specificity of 100.00% (23/23). Five proteins were differentially expressed between the NSCLC patients with brain metastases and the non-tumor patients. With one protein peak (m/z: 6050.00), these two samples could be discriminated with a sensitivity of 90.00% (9/10) and a specificity of 78.26% (18/23).

CONCLUSIONThe established diagnostic model of CSF protein fingerprint pattern provides high sensitivity and specificity in the diagnosis of NSCLC with brain metastasis.

Adult ; Aged ; Brain Neoplasms ; cerebrospinal fluid ; diagnosis ; secondary ; Carcinoma, Non-Small-Cell Lung ; cerebrospinal fluid ; diagnosis ; pathology ; secondary ; Cerebrospinal Fluid Proteins ; genetics ; Decision Trees ; Early Detection of Cancer ; Female ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; cerebrospinal fluid ; diagnosis ; pathology ; Male ; Middle Aged ; Peptide Mapping ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization