The Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway regulates cutaneous melanoma (CM) development and progression. The JAK1, JAK2, and STAT3 proteins are encoded by polymorphic genes. This study aimed to verify whether single-nucleotide variants (SNVs) in JAK1 (c.1648+1272G>A, c.991-27C>T), JAK2 (c.-1132G>T, c.-139G>A), and STAT3 (c.*1671T>C, c.-1937C>G) altered the risk, clinicopathological aspects, and survival of CM patients as well as protein activity.

CM patients (N = 248) and controls (N = 274) were enrolled in this study. Genotyping was performed by real-time polymerase chain reaction (PCR), and JAK1, JAK2, and STAT3 expression was assessed by quantitative PCR (qPCR). STAT3 c.-1937C>G SNV was investigated by luciferase, qPCR, western blot, apoptosis, and cell cycle assays in SKMEL-28 cells with CC or GG genotype.

Individuals with STAT3 c.*1671TT and c.-1937CC genotypes and TC haplotype of both SNVs were under about 2.0-fold increased risk of CM. Specific JAK1, JAK2, and STAT3 combined genotypes were associated with up to 4.0-fold increased risk of CM. Higher luciferase activity [4,013.34 vs. 2,463.32 arbitrary units (AU); p = 0.004], STAT3 expression by qPCR (649.20 vs. 0.03 AU; p = 0.003) and western blot (1.69 vs. 1.16 AU; p = 0.01), and percentage of cells in the S phase of the cell cycle (57.54 vs. 30.73%; p = 0.04) were more frequent in SKMEL-28 with STAT3 c.-1937CC than with GG genotype. CM cell line with CC genotype presented higher STAT3 protein levels than the one with GG genotype (1.93 versus 1.27 AU, p = 0.0027).

Our data present preliminary evidence that inherited abnormalities in the JAK/STAT pathway can be used to identify individuals at a high risk of CM, who deserve additional attention for tumor prevention and early detection.

• Fundação de Amparo à Pesquisa do Estado de São Paulo

• non‑small cell lung cancer
• glutathione S‑transferase ω1
• JAK
• STAT3
• proliferation
• migration
• invasion
• apoptosis

• A549 Cells
• Apoptosis
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/metabolism
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Movement
• Cell Proliferation
• Glutathione Transferase/genetics
• Glutathione Transferase/metabolism
• Humans
• Janus Kinases/genetics
• Janus Kinases/metabolism
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Neoplasm Invasiveness
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• STAT3 Transcription Factor/genetics
• STAT3 Transcription Factor/metabolism
• Signal Transduction

Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells.

• cancer therapy
• gastric cancer
• long non-coding RNA
• microRNA
• signal transducer and activator of transcription 3 (STAT3)
• tumor microenvironment

• Lung cancer
• Platinum-based chemotherapy
• Prognosis
• STAT3 rs4769793
• Susceptibility

To investigate the value of multiparameter joint analysis in the early diagnosis of gastric cancer (GC) in clinical practice.

Concentrations of CEA, CA724 and three kinds of cytokines (TNF-α, IL-6 and IL-8) in 176 GC patients, 117 atypical hyperplasia patients, and 204 healthy control individuals were used for building the diagnostic model, then 58 GC patients, 41 atypical hyperplasia patients, and 66 healthy control individuals were enrolled independently. The joints of the indicators were analyzed by binary logistic regression analysis method.

For discriminating the healthy control group and the GC group, IL-6 had the best diagnostic value, and the area under curve (AUC) of joint analysis was 0.95 (0.93-0.97). For the early stage and advanced stage GC, the AUC were 0.95 (0.92-0.98) and 0.95 (0.92-0.97). For discriminating the atypical hyperplasia group and GC group, CA724 had the best diagnostic value, and the AUC of joint analysis was 0.97 (0.95-0.99). For the early stage and advanced stage GC groups, the AUC were 0.98 (0.96-0.99) and 0.96 (0.94-0.98). After evaluation, for discriminating the GC, early stage GC and advanced cancer group from the healthy control group, the diagnostic sensitivity was 89.66%, 84.21% and 92.31%, respectively, and the specificity was 92.42%, 90.91% and 90.91%. For discriminating the GC, early stage GC and advanced cancer groups from the atypical hyperplasia group, the diagnostic sensitivity was 87.93%, 78.95% and 92.31%, respectively, and the specificity was 87.80%, 85.37% and 90.24%.

We have built a diagnostic model including CEA, CA724, IL-6, IL-8, and TNF-α. It may provide potential assistance as a screening method for the early detection of GC.

• Gastric cancer
• Atypical hyperplasia
• Serum
• Cytokine
• Early detection

• Biomarkers, Tumor/blood
• Biopsy
• Case-Control Studies
• Cytokines/blood
• Early Detection of Cancer/methods
• Female
• Gastroscopy
• Humans
• Hyperplasia/blood
• Hyperplasia/pathology
• Logistic Models
• Male
• Models, Biological
• Neoplasm Staging
• ROC Curve
• Stomach/diagnostic imaging
• Stomach/pathology
• Stomach Neoplasms/blood
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/pathology

The factors that predispose to pulmonary tuberculosis (PTB) are not fully understood. Previous studies have shown that cytokine gene polymorphisms were associated with PTB.

In this study, we have investigated the relationship between ILB, IL6, and TNFα polymorphisms and a predisposition to Mycobacterium tuberculosis (MTB) infection and PTB.

A total of 209 cases of PTB, 201 subjects with latent TB infection (LTBI), and 204 healthy controls (HCS) were included in this study. Logistic regression analyses under allelic, homozygous, and heterozygous models were used to calculate P values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk, adjusting for sex and age. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR) method.

When comparing PTB patients with LTBI subjects, significant associations with disease development were observed for SNPs of IL6 and TNFα. When comparing LTBI subjects with HCS, IL1B polymorphisms were significantly associated with LIBI. Haplotype analyses suggested that the CGG haplotype of IL1B was associated with an increased risk of PTB (P = 0.039, OR = 1.34, 95% CI: 1.01–1.76), while the TTGCG haplotype of TNFα was a protective factor against PTB (P = 0.039, OR = 0.66, 95% CI: 0.44–0.98).

Our study demonstrated that IL1B variants were related to LTBI and IL6 and TNFα variants were associated with PTB.

MicroRNAs (miRNAs), a group of small, non-protein coding, endogenous RNAs, play critical roles in the tumorigenesis and progression of human cancer. miR-216a has recently been reported to play an oncogenic role in human cancer. While, the expression of miR-216a, its biological function and underlying molecular mechanisms in gastric cancer (GC) are largely unknown. In this study, we revealed that miR-216a was underexpressed in GC tissues compared to matched noncancerous tissues. Decreased levels of miR-216a were confirmed in GC cell lines compared with a normal gastric epithelium cell line. miR-216a underexpression was associated with malignant prognostic features including lymph node metastasis, venous infiltration, invasive depth and advanced TNM stage. GC patients with low miR-216a level showed an obvious shorter overall survival. miR-216a overexpression restrained migration and invasion of MGC-803 cells, while its knockdown exerted opposite effects on metastatic behaviors of SGC-7901 cells. In vivo experiments found that miR-216a restoration reduced metastatic nodes of GC cells in nude mice liver. miR-216a notably suppressed epithelial-mesenchymal transition (EMT) of GC cells. Janus kinase 2 (JAK2) was recognized as a direct target and downstream mediator of miR-216a in GC cells. Interestingly, JAK2/signal transducer and activator of transcription 3 (STAT3) pathway was prominently inactivated by miR-216a and probably mediated the role of miR-216a in the regulation of migration, invasion and EMT process of GC cells. In conclusion, these data suggest that miR-216a functions as a tumor suppressive miRNA in the development of GC possibly by targeting JAK2/STAT3-mediated EMT.

• JAK2/STAT3
• epithelial-mesenchymal transition
• gastric cancer
• miR-216a
• tumor metastasis

• Air Pollution/statistics & numerical data
• Biomarkers/blood
• Child
• Cytokines/blood
• Environmental Exposure/statistics & numerical data
• Gene Expression
• Humans
• Hypersensitivity
• Interleukin-10/blood
• Interleukin-6/blood
• Nitrogen Dioxide/analysis
• Particulate Matter/analysis
• Vehicle Emissions/analysis

• deregulation
• gastric cancer
• gene expression
• mRNA
• therapeutic targets

• Gastric cancer
• Kaplan–Meier
• LASSO
• Prognosis
• Survival analysis

• Gene Expression Profiling
• Humans
• Prognosis
• Risk Factors
• Stomach Neoplasms/genetics
• Survival Analysis

• gastric cancer
• genetic variants
• interleukin-17
• molecular epidemiology
• susceptibility

• Asian People/genetics
• Case-Control Studies
• Cell Line, Tumor
• Chi-Square Distribution
• China
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Haplotypes
• Heterozygote
• Homozygote
• Humans
• Interleukin-17/genetics
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci
• RNA, Messenger/genetics
• Risk Assessment
• Risk Factors
• Stomach Neoplasms/ethnology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/immunology