Adenocarcinoma ; classification ; genetics ; pathology ; Forecasting ; Humans ; Lung ; pathology ; Lung Neoplasms ; classification ; genetics ; pathology

Adenocarcinoma ; genetics ; pathology ; Adenoma ; genetics ; pathology ; Colonic Polyps ; genetics ; pathology ; Colorectal Neoplasms ; genetics ; pathology ; Humans ; Microsatellite Instability ; Mutation ; Precancerous Conditions ; genetics ; pathology ; Proto-Oncogene Proteins B-raf ; genetics

BACKGROUND: m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD. METHODS: LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases. RESULTS: The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues. CONCLUSIONS m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.
Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/pathology* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/pathology* ; Methylation ; Tumor Microenvironment/genetics*

OBJECTIVETo correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas.

METHODSAccording to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated.

RESULTSMutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type.

CONCLUSIONLung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

Adenocarcinoma ; genetics ; pathology ; Adenocarcinoma, Mucinous ; genetics ; pathology ; Adenocarcinoma, Papillary ; genetics ; pathology ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis ; Male ; Mutation ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking

Due to emphasis on early screening for lung cancer, the detection rate of multiple ground glass opacities (GGOs) on computed tomography (CT) image increases in recent years, and research on multifocal adenocarcinomas presented by GGOs has been thriving. It is more common in women and non-smokers and has excellent prognosis both in patients with natural history and after surgery. These clinical features suggest that it is likely to be a distinct disease entity. From the perspective of molecular genetics, lesions in the same individual are likely to have distinct clonal features. Therefore, genetic heterogeneity is the most prominent feature of multifocal pulmonary adenocarcinomas with GGOs. The genetic heterogeneity is expected to assist the diagnosis of multifocal pulmonary adenocarcinoma and intrapulmonary metastasis, and also suggests that genetic testing of the GGO lesions is of great therapeutic significance. Some GGO lesions may harvest the similar clonal feature, which provide new evidence for the theory of spread through air spaces (STAS).
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Adenocarcinoma ; diagnostic imaging ; genetics ; pathology ; Adenocarcinoma of Lung ; Humans ; Lung Neoplasms ; diagnostic imaging ; genetics ; pathology ; Retrospective Studies ; Solitary Pulmonary Nodule ; diagnostic imaging ; genetics ; pathology ; Tomography, X-Ray Computed

Adenocarcinoma ; classification ; genetics ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; pathology ; Exons ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; genetics ; ras Proteins ; genetics

OBJECTIVETo investigate the effect of functional blocking of endogenous miR-23a with a specific antisense oligonucleotide (ASO) on the proliferation and invasiveness of gastric adenocarcinoma cell line MGC803 in vitro.

METHODSA specific ASO targeting miR-23a, namely ASO-23a, was transfected into MGC803 cells to block endogenous miR-23a. The mRNA level of miR-23a in the transfected cells was detected with quantitative real-time PCR. The changes of cell proliferation following the transfection were detected with MTT assay and colony formation assay, and TUNEL assay and Transwell assay were employed to evaluate the changes in cell apoptosis and invasiveness, respectively.

RESULTSQuantitative real-time PCR demonstrated efficient functional blocking of endogenous miR-23a in MGC803 cells by ASO-23a. Suppression of miR-23a with ASO-23a obviously inhibited cell growth, colony formation and invasiveness of MGC803 cells and significantly enhanced the cell apoptosis.

CONCLUSIONASO-23a can efficiently block the function of endogenous miR-23a in MGC803 cells to inhibit cell proliferation and invasion and promote cell apoptosis.

Adenocarcinoma ; genetics ; pathology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; MicroRNAs ; genetics ; Oligonucleotides, Antisense ; Stomach Neoplasms ; genetics ; pathology ; Transfection

Adenocarcinoma ; genetics ; pathology ; Adenoma ; genetics ; pathology ; Cell Cycle Proteins ; biosynthesis ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; Disease Progression ; Humans ; Intracellular Signaling Peptides and Proteins ; Lymph Nodes ; pathology ; Lymphatic Metastasis

Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized treatment plan should be taken to improve outcomes.
Adenocarcinoma ; pathology ; Aged ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; genetics ; pathology ; surgery ; Humans ; Laparoscopy ; Mutation ; Risk Factors

Adenocarcinoma, Follicular ; genetics ; metabolism ; pathology ; Biomarkers, Tumor ; genetics ; Diagnosis, Differential ; Humans ; Matrix Metalloproteinase 1 ; biosynthesis ; genetics ; Telomerase ; biosynthesis ; genetics ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; ras Proteins ; biosynthesis ; genetics