Pancreatic adenocarcinoma (PAAD) has been a huge challenge to public health due to its increasing incidence, frequent early metastasis, and poor outcome. The molecular basis of tumorigenesis and metastasis in PAAD is largely unclear. Here, we identified a novel tumor-suppressor long noncoding RNA (lncRNA) MBNL1-AS1, in PAAD and revealed its downstream mechanism. Quantitative real-time PCR (qRT-PCR) data showed that MBNL1-AS1 expression was significantly downregulated in PAAD tissues and cells, which was closely associated with metastasis and poor prognosis. Cell counting kit-8 (CCK-8) assay, transwell assay, and western blot verified that overexpression of MBNL1-AS1 suppressed cell proliferation, migration, and epithelial mesenchymal transformation (EMT) behavior in PAAD cells. By using a dual luciferase reporter gene system, we confirmed that miR-301b-3p was a direct target of MBNL1-AS1. Further mechanismic study revealed that upregulation of miR-301b-3p abolished the inhibitory effect of MBNL1-AS1 overexpression on cell proliferation, tumorigenesis, migration and EMT. Our results demonstrate that MBNL1-AS1 plays a tumor-suppressive role in PAAD mainly by downregulating miR-301b-3p, providing a novel therapeutic target for PAAD.

Kidney renal clear cell carcinoma (KIRC) is increasing in incidence worldwide, with poor and unpredictable patient prognosis limited by diagnostic and therapeutic approaches. New genes are urgently needed to improve this situation. The ankyrin repeat and suppressor of the cytokine signaling (SOCS) box (ASB) family are a promising class of tumorigenesis-related genes. We examined the expression and mutation of 18 ASB genes in various tumors for this study. The findings revealed that ASB genes exhibit significant copy number variation (CNV) and single nucleotide variation (SNV). There were substantial variations in ASB gene expression in different tumor tissues, and different levels of methylation of ASB genes affected the gene expression and tumor progression. By applying LASSO regression analysis, we established a KIRC survival model based on five ASB genes (ASB6, ASB7, ASB8, ASB13, and ASB17). Additionally, ROC curve analysis was used to assess the survival model’s accuracy. Through univariate and multivariate COX regression analysis, we demonstrated that the model’s risk score might be an independent risk factor for individuals with KIRC. In summary, our KIRC survival model could accurately predict patients’ future survival. Further, we also quantified the survival model through a nomogram. This series of findings confirmed that ASB genes are potential predictive markers and targeted therapies for KIRC. Our KIRC survival model based on five ASB genes can help more clinical practitioners make accurate judgments about the prognosis of KIRC patients.

Objective. The purpose of our work was to explore the association of mutations in the androgen receptor gene and copy numbers of the androgen-receptor silk protein A complex with glutathione-S-transferases T1 and M1 in prostate cancer patients. Materials and Methods. Eighty-five patients with PC and 85 healthy controls were included in the study. Fasting peripheral venous blood was collected, whole blood genomic DNA was extracted, and AR gene-receptor genotype was detected by a high-resolution melting curve analysis detection technology. Expression levels of androgen receptor (AR) and filamin protein A (FlnA) were detected by Western blotting. RT-PCR was used to detect the copy number of T1 and M1 glutathione-S-transferases. Results. The wild-type androgen receptor gene rs5918762 is of TT type. The frequencies of CC and TC genes in the prostate cancer group were significantly higher than those in the normal control group (P < 0.05). Compared with TT-type PC patients, PC patients with TC-type and CC-type had higher expression levels of sex hormone receptor silk protein A complex and higher copy numbers of GSTT1 and GSTM1 (P < 0.05). Androgen-receptor gene mutation (T ⟶ C) was significantly positively correlated with the expression level of androgen-receptor silk protein A complex and the copy number of GSTT1 and GSTM1. Conclusion. Androgen-receptor gene polymorphisms were significantly associated with expression levels of androgen receptor complex A and silk proteins, and copy numbers of T1 and M1 glutathione-S-transferases. A combination of four factors can be used to identify prostate cancer susceptibility and disease progression.

Background. Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC) with a low 5-year survival rate, which may be associated with the presence of metastatic tumors at the time of diagnosis, especially lymph node metastasis (LNM). This study aimed to construct a LNM-related gene signature for predicting the prognosis of patients with LUAD. Methods. RNA sequencing data and clinical information of LUAD patients were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Samples were divided into metastasis (M) and nonmetastasis (NM) groups based on LNM status. Differentially expressed genes (DEGs) between M and NM groups were screened, and then WGCNA was applied to identify key genes. Furthermore, univariate Cox and LASSO regression analyses were conducted to construct a risk score model, and the predictive performance of model was validated by GSE68465, GSE42127, and GSE50081. The protein and mRNA expression level of LNM-associated genes were detected by human protein atlas (HPA) and GSE68465. Results. A prognostic model based on eight LNM-related genes (ANGPTL4, BARX2, GPR98, KRT6A, PTPRH, RGS20, TCN1, and TNS4) was developed. Patients in the high-risk group had poorer overall survival than those in the low-risk group, and validation analysis showed that this model had potential predictive value for patients with LUAD. HPA analysis supported the upregulation of ANGPTL4, KRT6A, BARX2, RGS20 and the downregulation of GPR98 in LUAD compared with normal tissues. Conclusion. Our results indicated that the eight LNM-related genes signature had potential value in the prognosis of patients with LUAD, which may have important practical implications.

Background. Complex regulation exists between tumor metabolism and M2 macrophages. Long noncoding RNAs (lncRNAs) are famous for their wide regulatory role. This study aimed to identify the lncRNAs involved in the crosstalk between tumor metabolism and M2 macrophages. Methods. The Cancer Genome Atlas was responsible for the public data. R software was responsible for the analysis of public data. Results. Based on the input expression profile, we quantified the M2 macrophage infiltration using the CIBERSORT algorithm and found that M2 macrophages were a risk factor for lung cancer. Also, we found that M2 macrophages were correlated with multiple metabolism pathways. Then, 67 lncRNAs involved in both M2 macrophages and related metabolism pathways were identified. A prognosis signature based on AC027288.3, AP001189.3, FAM30A, GAPLINC, LINC00578, and LINC01936 was established, which had good prognosis prediction ability. The clinical parameters and risk score were combined into a nomogram plot for better prediction of the patient’s prognosis. A high fit of actual survival and nomogram-predicted survival was found using the calibration plot. Moreover, in low-risk patients, immunotherapy was more effective, while cisplatin and docetaxel were more effective in high-risk patients. Biological enrichment analysis indicated pathways of notch signaling, TGF-β signaling, interferon alpha response, and interferon-gamma response were activated in the high-risk group. Meanwhile, the risk score was associated with tumor metabolism and M2 macrophages. Also, we found that the promoting effect of CAPLINC on M2 macrophage polarization might act through multiple metabolism pathways. Conclusions. Our result can provide new insights into the interaction between M2 macrophages and tumor metabolism, as well as the involved lncRNAs, which can provide the direction for future studies.

Chinese herbal medicine (CHM), which includes herbal slices and proprietary products, is widely used in China. Shenqi Dihuang (SQDH) is a traditional Chinese medicine (TCM) formula with ingredients that affect tumor growth. Despite recent advances in prognosis, patients with renal cell carcinoma (RCC) cannot currently receive curative treatment. The present study aimed to explore the potential target genes closely associated with SQDH. The gene expression data for SQDH and RCC were obtained from the TCMSP and TCGA databases. The SQDH-based prognostic prediction model reveals a strong correlation between RCC and SQDH. In addition, the immune cell infiltration analysis indicated that SQDH might be associated with the immune response of RCC patients. Based on this, we successfully built the prognostic prediction model using SQDH-related genes. The results demonstrated that CCND1 and NR3C2 are closely associated with the prognosis of RCC patients. Finally, the pathways enrichment analysis revealed that response to oxidative stress, cyclin binding, programmed cell death, and immune response are the most enriched pathways in CCND1. Furthermore, transcription regulator activity, regulation of cell population proliferation, and cyclin binding are closely associated with the NR3C2.

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT (p > 0.05). The same trend was observed when the analysis was extended to other genetic models, including dominant (p = 0.50), recessive (p = 0.87), and additive (p = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples.

Background. In Ethiopia, livestock contributes 45% of agricultural GDP. Despite the economic role played by the sector, there have been little efforts to genetically improve the indigenous cattle. Morphological characterization of selected Ethiopian indigenous cattle has been made for (Bonga, Jimma, and Kerayu) cattle types. But, the selected indigenous cattle were not characterized at molecular level (genetic diversity information). Hence, this work was initiated to detect and determine the genetic diversity and population structure of selected Ethiopian indigenous cattle ecotypes using microsatellite markers. Results. Different alleles were identified (131) and thirty-three of these alleles were unique to specific ecotypes. All loci used were informative with PIC values ranging from 0.5 (TGLA126) to 0.84 (ETH10) with a mean of 0.70 per locus. The Shannon information index ranged from (I = 1.02) ILST006 to (I = 1.63) ETH10 with an average of 1.28 revealing there is genetic diversity. Moreover, analysis of molecular variance (AMOVA) revealed 84% genetic variation within a population and 13% variation among populations. The value of F-statistics (Fst) (0.129 = 13%) indicated that there was moderate genetic differentiation among ecotypes. The (UPGMA) revealed, Bonga and Jimma clustered together while Kerayu cattle were relatively distinct, Principal coordinates analysis (PCOA) and structure analysis grouped the individual into different clusters confirming the presence of ecotype admixture due to geographical origins and uncontrolled mating. Conclusion. In general, this study has successfully characterized the genetic diversity and population structure of Bonga, Jimma, and Kerayu cattle ecotypes using high polymorphic/informative microsatellite markers. According to this study, Kerayu cattle have high AR and PA when compared to Bonga and Jimma cattle populations. So, the Kerayu population is more diverse than others and it is the hotspot for genetic diversity study. The generated information is very relevant for breeder and genetic conservation.

Background. Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods. From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results. We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions. The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Background. Cytochrome P450 complex plays a key role in drug metabolism. CYP2B6 has an essential part in Cytochrome P450 complex metabolism. This study aims to determine the allelic distribution of CYP2B6∗2 and CYP2B6∗3 in three main Iranian ethnicities: Fars, Turk, and Kurd. Methods. The study was conducted on 174 unrelated healthy volunteers from three main Iranian ethnicities. After DNA extraction from peripheral blood samples, genotyping of CYP2B6∗2 and ∗3 was performed using tetra ARMS and ARMS PCR, respectively. Results. The average age of 174 cases was 40.69 ± 11.87 (mean ± SD) and 39.06 ± 11.63 (mean ± SD) for males and females. In the CYP2B6∗2 variant, the genotyping frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 8.7%, 86%, and 5.2%, respectively. The CYP2B6∗2 (c.64C > T) allele frequency was 48.2% (95% CI: (37.8–58.6)). In the CYP2B6∗3 variant, the frequency of wild type (C/C), heterozygous (C/T), and homozygous mutant (T/T) was 75.3%, 11%, and 13.6%, respectively. The CYP2B6∗3 (c.777C > A) allelic frequency was 19.1% (95% CI: (17.5–20.7)). Conclusion. Allelic distribution in three main Iranian ethnicities, i.e., Turk, Kurd, and Fars, is remarkably higher than that in other populations, even that in Southern Iran. High frequencies of CYP2B6∗2 and ∗3 in the Iranian population highly affect drug responsiveness. Understanding such variability could help to increase drug efficacy and reduce its toxicity.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 *)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Its etiopathogenesis is complex, mainly influenced by genetic instability caused by the accumulation of mutations. The XRCC1 gene, which is involved in DNA repair, has been associated with CRC through the R194W (C194T) and R399Q (G399A) polymorphisms, but the results are inconsistent. Here, we analyzed the association of these polymorphisms with sporadic CRC in a northeastern Mexican population, including 155 male CRC patients and 155 male controls. Genotyping was performed using the RFLP method. An association with CRC was found for the 399A allele (G vs A; OR = 1.48 (1.03–2.13), P = 0.034) and for the 399AA genotype in a codominant model (AA vs GG; OR = 3.11 (1.06–9.10), P = 0.031). In contrast, there were no significant differences between CRC patients and controls for the C194T polymorphism (C vs T; OR = 0.82 (0.52–1.31), P = 0.41). These results are consistent with many similar studies, but further research is needed to verify whether the XRCC1 R194W and R399Q polymorphisms play a role in CRC etiology. The functional significance of these polymorphisms is unclear, but some studies suggest that they influence DNA repair capacity and, thus, cancer risk.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid neoplasms, characterized by evidence of follicular cell differentiation. Orthodenticle homeobox 1 (OTX1) is a transcription factor which has been implicated in numerous diseases, including malignancies. The objective of this research was to explore the function of OTX1 in PTC. Immunohistochemistry (IHC) was employed to determine the protein level of OTX1 in PTC specimens. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, a xenograft model on nude mice was established to investigate in vivo effects of OTX1. Our results revealed that OTX1 was significantly upregulated within specific PTC tissues and was remarkably correlated with unfavorable clinical outcomes in PTC. Silencing OTX1 resulted in a significant inhibition in cell viability and suppressed cell proliferation. In addition, in vivo experiments demonstrated that OTX1 silencing resulted in a significant suppression of tumor growth in nude mice. Collectively, these results suggest that OTX1 may play crucial roles in promoting PTC progression.

Introduction. Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban’s ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance. Methods. We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test’s p value was higher than 0.1. We used random models when the p value was less than 0.1. Results. Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations. Conclusion. This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.

Glioma is a highly aggressive form of brain cancer characterized by limited treatment options and poor patient prognosis. In this study, we aimed to elucidate the oncogenic role of thymosin beta-10 (TMSB10) in glioma through comprehensive analyses of patient data from the TCGA and GTEx databases. Our investigation encompassed several key aspects, including the analysis of patients’ clinical characteristics, survival analysis, in vitro and in vivo functional experiments, and the exploration of correlations between TMSB10 expression and immune cell infiltration. Our findings revealed a significant upregulation of TMSB10 expression in glioma tissues compared to normal brain tissues, with higher expression levels observed in tumors of advanced histological grades. Moreover, we observed positive correlations between TMSB10 expression and patient age, while no significant association with gender was detected. Additionally, TMSB10 exhibited marked elevation in gliomas with wild-type IDH and noncodeletion of 1p/19q. Survival analysis indicated that high TMSB10 expression was significantly associated with worse overall survival, disease-specific survival, and progression-free survival in glioma patients. Functionally, knockdown of TMSB10 in glioma cells resulted in reduced cellular growth rates and impaired tumor growth in xenograft models. Furthermore, our study revealed intriguing correlations between TMSB10 expression and immune cell infiltration within the tumor microenvironment. Specifically, TMSB10 showed negative associations with plasmacytoid dendritic cells (pDC) and γδ T cells (Tgd), while displaying positive correlations with neutrophils and macrophages. These findings collectively provide valuable insights into the oncogenic properties of TMSB10 in glioma, suggesting its potential as a therapeutic target and a biomarker for patient stratification.

Background. Health and economies are both affected by the coronavirus disease-19 (COVID-19) global pandemic. Angiotensin-converting enzyme 2 (ACE2) is a polymorphic enzyme that is a part of the renin-angiotensin system, and it plays a crucial role in viral entry. Previous investigations and studies revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ACE2 have a considerable association. Recently, ACE2 variants have been described in human populations in association with cardiovascular and pulmonary conditions. In this study, genetic susceptibility to COVID-19 in different populations was investigated. Methods and Results. We evaluated the identified variants based on the predictive performance of 5 deleteriousness-scoring methods and the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. The results indicated 299 variants within the ACE2 gene. The variants were analyzed by different in-silico analysis tools to assess their functional effects. Ultimately, 5 more deleterious variants were found in the ACE2 gene. Conclusions. Collecting more information about the variations in binding affinity between SARS-CoV-2 and host-cell receptors due to ACE2 variants leads to progress in treatment strategies for COVID-19. The evidence accumulated in this study showed that ACE2 variants in different populations may be associated with the genetic susceptibility, symptoms, and outcome of SARS-CoV-2 infection.

This research delves into the implications of the RNA binding motif, single stranded interacting protein 2 (RBMS2)—a gene associated with tumor-suppressing functions—in the context of kidney renal clear cell carcinoma (ccRCC). Through meticulous exploration of online databases, we have identified a negative association between RBMS2 expression and adverse clinico-pathological features, such as advanced TNM stage. Furthermore, our findings indicate that RBMS2 acts as a prognostic predictor for clinical outcomes in ccRCC, evidenced by both univariate and multivariate analyses. Cellular assays have corroborated these findings, revealing that an overexpression of RBMS2 curtails ccRCC cell proliferation and migration. Additionally, our research has unearthed links between RBMS2 and immune infiltration within the ccRCC tumor microenvironment. Collectively, our results underscore the tumor-inhibiting role of RBMS2 in ccRCC and spotlight its potential as a prognostic marker and therapeutic intervention target.

Background. Hepatocellular carcinoma (HCC) presents significant challenges in diagnosis and treatment. Understanding the role of PANoptosis-related molecules in HCC is crucial for advancing therapeutic strategies. Methods. We conducted a comprehensive analysis using public data from the Cancer Genome Atlas, Human Protein Atlas, Tumor Immune Single Cell Hub, and STRING databases. Techniques included Kaplan–Meier survival curves, Cox regression, LASSO analysis, and various computational methods for understanding the tumor microenvironment. We also employed ClueGO, gene set enrichment analysis, and other algorithms for biological enrichment analysis. Results. CASP8 emerged as a significant molecule in HCC, correlated with poor survival outcomes. Its expression was predominant in the nucleoplasm and cytosol and varied across different cancer types. Biological enrichment analysis revealed CASP8’s association with critical cellular activities and immune responses. In the tumor microenvironment, CASP8 showed correlations with various immune cell types. A nomogram plot was developed for better clinical prognostication. Mutation analysis indicated a higher frequency of TP53 mutations in patients with elevated CASP8 expression. In addition, CASP8 was found to regulate YEATS2 in HCC, highlighting a potential pathway in tumor progression. Conclusions. Our study underscores the multifaceted role of CASP8 in HCC, emphasizing its prognostic and therapeutic significance. The regulatory relationship between CASP8 and YEATS2 opens new avenues for understanding HCC pathogenesis and treatment strategies.