The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Humans ; Triple Negative Breast Neoplasms/genetics* ; MicroRNAs/genetics* ; Oncogenes ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement

The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research.
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Humans ; Lung ; Lung Diseases ; Lung Neoplasms ; Microbiota ; Oncogenes

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.
Animals ; Carcinoma, Papillary/genetics* ; Humans ; Lymphatic Metastasis ; Mice ; Mutation ; Oncogenes ; Proto-Oncogene Proteins B-raf/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

OBJECTIVES: The biomarkers targeting colorectal cancer (CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC. METHODS: GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa (CRM) tissues from the NCBI-GEO database, and the differentially expressed genes (DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC. RESULTS: For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets (|log CONCLUSIONS The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.
Biomarkers, Tumor/metabolism* ; Colorectal Neoplasms/genetics* ; Computational Biology ; Formins ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Glycoproteins ; Humans ; Intercellular Signaling Peptides and Proteins ; Oncogenes ; Prognosis ; Protein Interaction Maps

Immune checkpoint inhibitors (ICIs) have shown remarkable benefit in the treatment of patients with non-small-cell lung cancer (NSCLC) and have emerged as an effective treatment option even in the first-line setting. ICIs can block inhibitory pathways that restrain the immune response against cancer, restoring and sustaining antitumor immunity. Currently, there are 4 PD-1/PD-L1 blocking agents available in clinics, and immunotherapy-based regimen alone or in combination with chemotherapy is now preferred option. Combination trials assessing combination of ICIs with chemotherapy, targeted therapy and other immunotherapy are ongoing. Controversies remain regarding the use of ICIs in targetable oncogene-addicted subpopulations, but their initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the choice. For the majority of patients without targetable driver oncogenes, deciding between therapeutic options can be difficult due to lack of direct cross-comparison studies. There are continuous efforts to find predictive biomarkers to find those who respond better to ICIs. PD-L1 protein expressions by immunohistochemistry and tumor mutational burden have emerged as most well-validated biomarkers in multiple clinical trials. However, there still is a need to improve patient selection, and to establish the most effective concurrent or sequential combination therapies in different NSCLC clinical settings. In this review, we will introduce currently used ICIs in NSCLC and analyze most recent trials, and finally discuss how, when and for whom ICIs can be used to provide promising avenues for lung cancer treatment.
Biomarkers ; Carcinoma, Non-Small-Cell Lung ; Drug Therapy ; Humans ; Immunohistochemistry ; Immunotherapy ; Lung Neoplasms ; Oncogenes ; Patient Selection ; Protein-Tyrosine Kinases

Enhancer of zeste homolog 2(EZH2) is a histone methyltransferase which regulate gene expression through epigenetic machinery. The abnormal expression of EZH2 has been described in many cancer types. With in-depth study, it was found that EZH2 is involved in the occurrence and development in many kinds of malignant hematologic disease which may play a dual role of oncogenes and tumor suppressor genes. In recent years, the emergence of EZH2 inhibitors provide a new option for the future treatment of hematological malignancies. In this review, the expression and clinical significance of EZH2 in various of hematological tumors were summarized briefly.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Hematologic Neoplasms/genetics* ; Humans ; Neoplasms ; Oncogenes ; Research

Although the exact etiology of cutaneous angiosarcoma remains unclear, MYC gene amplification has been recently discovered as a new pathogenesis. MYC is a proto-oncogene, and aberration of MYC signaling in malignancies is associated with tumor metastasis, recurrence, and mortality. Moreover, upregulation of the miRNA polycistron, miR-17-92 cluster, were confirmed in both cutaneous angiosarcoma and multiple myeloma with MYC amplification. The correlation between MYC and miRNA expression is predictable as the coincident aberrant phenotype in two diseases. Moreover, the exploiting MYC dependency may be an attractive disease-specific strategy for the diagnosis and treatment of patients who are unaware of the causes of cutaneous angiosarcoma. Herein, a rare case of cutaneous angiosarcoma of the foot, which is also the first case of cutaneous angiosarcoma accompanied by multiple myeloma, has been described.
Diagnosis ; Foot ; Genes, myc ; Hemangiosarcoma ; Humans ; MicroRNAs ; Mortality ; Multiple Myeloma ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogenes ; Recurrence ; Up-Regulation

A variety of clonal cytogenetic abnormalities have been reported in aggressive natural killer (NK)-cell lymphoma and leukemia. Recent chromosomal microarray studies have shown both gain and loss of 1q and loss of 7p as recurrent abnormalities in aggressive NK-cell leukemia. Here, we report a case of aggressive NK-cell leukemia with complex chromosomal gains and losses, as confirmed by chromosomal microarray analysis. The patient showed an aggressive clinical course, which was complicated by hemophagocytic lymphohistiocytosis. Conventional cytogenetic analysis revealed trisomy 3 and 1q gain only. However, chromosomal microarray analysis detected an additional gain of 1q21.1–q24.2 and a loss of 1q24.2–q31.3. These abnormal lesions might play a role in the pathogenesis of aggressive NK-cell leukemia by inactivating tumor suppressor genes or by activating oncogenes. These results suggest that chromosomal microarray analysis may be used to provide further genetic information for patients with hematological malignancies, including aggressive NK-cell leukemia.
Chromosome Aberrations ; Cytogenetic Analysis ; Genes, Tumor Suppressor ; Hematologic Neoplasms ; Humans ; Leukemia ; Lymphohistiocytosis, Hemophagocytic ; Lymphoma ; Microarray Analysis ; Oncogenes ; Trisomy

Medulloblastoma is considered one of the most threatening malignant brain tumors with an extremely high mortality rate in children. In the medulloblastoma, there are several genes and mutations found to work in an unregulated manner that works together to push the cells into a cancerous state. With the discovery of non-coding RNAs such as microRNAs (miRNAs), it has been shown that a different layer of gene regulations may be disrupted which would cause cancer. This fact led scientists to put their focus on the role of miRNAs in cancer. A mature miRNA contains a seed sequence which gives the miRNA to identify and attach to the interest mRNA; this attachment may lead degradation of mRNA or suppress of translation of the mRNA. The expression of miRNAs in medulloblastoma shows that some of these non-coding RNAs are overexpressed (OncomiRs) which help cells to proliferate and keep their stemness features. On the other hand, there are other forms of these miRNAs which normally inhibit cell proliferation and promote cell differentiation (tumor suppressor). These are down-regulated during cancer progression. In this systematic review, we attempted to gather several important studies on miRNAs’ role in medulloblastoma tumors and the importance of these non-coding RNAs in the future study of cancer.
Brain Neoplasms ; Cell Differentiation ; Cell Proliferation ; Child ; Genes, Tumor Suppressor ; Hand ; Humans ; Medulloblastoma ; MicroRNAs ; Mortality ; Oncogenes ; RNA, Messenger ; RNA, Untranslated ; Social Control, Formal