Cancer Development Research Articles

Palliative care resources utilized in patients with liver cancer with cirrhosis: Trend in National Inpatient Sample (NIS) study (2016–2020).

59 Background: Liver cancer is the fourth cause of cancer death in the world. Hepatocellular carcinoma represents around 90% of all liver cancer, with an increase in incidence and a worsening survival rate over the years. Liver cirrhosis is the major risk factor for liver cancer development. Early involvement in palliative care/hospice care focusing on quality of life, is associated with improved physical and psychological symptoms and improvement in caregiver stress and bereavement. We examined as primary outcome the utilization and trend of palliative care (PC) among hospitalized patients with liver cancer and cirrhosis using the NIS. Methods: This is a retrospective study using NIS data from 2016 to 2021. We included patients aged 18 years or older who were admitted with a diagnosis of malignancy of the liver and the intrahepatic bile duct and who also had a diagnosis of fibrosis and cirrhosis of the liver. Patients who had a PC encounter during hospitalization were identified. The cohort was divided between patients with PC encounters and those without PC encounters. Cohorts were matched in a 1:1 ratio with no replacement using propensity scores. Total charges during hospitalization, length of stay (LOS), mortality, and disposition were measured as outcomes. Results: A total of 53,475 admissions with a diagnosis of liver malignancy and liver cirrhosis were identified. Of those, 20.8% had an encounter with a PC. The mean age of those with a PC encounter was 65.1 years (SD±7.86), while the mean age for those without was 64.5 years (SD±7.35). Sex and race were similar between both cohorts. Patients with PC encounters had a higher mean Elixhauser index (6.43 vs 5.58, p < 0.001) than those without a PC encounter. Patients with PC encounters had lower total hospital charges ($70,988 vs $94,518, p < 0.001), longer LOS (6.83 vs. 5.82 days, p < 0.001), and higher odds of mortality (aOR 7.20, CI 5.56- 9.32, p < 0.001) compared to those without a PC encounter. Patients with a PC encounter were more frequently discharged to a long-term facility (23.9% vs. 12.6%) or with home health care (36.1% vs. 18.4%) and less often had a routine hospital discharge (13.5% vs. 60.1%), compared to those without a PC encounter. Conclusions: This study highlights the impact of PC on patients hospitalized with liver malignancy and cirrhosis. Despite being underutilized, with only 20.8% of patients receiving PC, those who do experienced lower hospital charges, longer hospital stays, and higher in- hospital mortality. These findings suggest that PC focuses on symptom management and quality of life rather than extending life expectancy. Patients receiving PC are more frequently discharged to long-term care or home health care, indicating a shift towards supportive care. The results advocate for the broader and earlier integration of palliative care in treating liver cancer and cirrhosis to improve patient outcomes and support.

Hyperactive Dendritc Cells Redirect Aged Antitumor Immunity.

Aging is one of the biggest risk factors for cancer development. More than 85% of all cancers occur in individuals above 55 years old, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis. However, the aging-associated defects in antitumor immunity, particularly with regard to T cells, remain underexplored. Recent findings by Zhivaki and colleagues suggest that age-related immune defects affecting antitumor responses involve reduced levels of CD8+ T cells and compromised dendritic cell (DC) functions such as antigen presentation and migration. Their study demonstrates that a hyperactive DC vaccine can restore DC functions in older mice. Furthermore, these hyperactive DCs, characterized by increased IL1β production and better migratory capability to the lymph node, promote the development of cytolytic CD4+ T cells exhibiting Th1-like phenotypes. This research reveals mechanisms underlying the response to hyperactive DC vaccines in older mice and highlights the critical role of cytolytic CD4+ T cells as substitutes for CD8+ T cells in driving antitumor immunity and achieving long-term tumor control in older mice.

Upregulation Mechanism of CCND1 in Apoptosis on MCF-7 Cell Line upon Treatment with Quranic Verses

INTRODUCTION: Ruqyah Shar'iyyah, one of the complementary and alternative medicine (CAM) has shown therapeutic benefits in breast cancer by utilizing Quranic verses in reducing symptoms and enhancing their quality of life as a result of invasive standard therapies. However, scientific evidence is required to demonstrate Ruqyah Shar'iyyah's effectiveness on gene expression and molecular pathways in carcinogenesis. Therefore, this study was conducted to evaluate the effectiveness of Ruqyah Shar’iyyah on breast cancer cell line on apoptosis and CCND1 expression in related signaling pathways. MATERIALS AND METHODS : MCF-7 cell lines were treated with direct recitation of several Quranic verses for 12 hours and 24 hours. Cell viability was observed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of CCND1 was determined using RT-qPCR technique. The molecular mechanism and signalling pathways were evaluated using Reactome database for in silico analysis. RESULTS: Cell viability data showed 95.69% and 93.54% exhibiting slight reduction for 12-hour treatment in untreated and treated MCF-7, respectively. Meanwhile more reduction was observed in 24-hour treatment with 95.11% in untreated cell line as compared to 92.34% in treated cell line. The cell morphology also exhibited apoptotic activity in the treated group for both two time points. Gene expression analysis of CCNDI also demonstrated upregulation with 1.81-fold change. The data was supported by the in-silico analysis in which 25 relevant significant signalling pathways related to CCND1 highlighting the role of the gene in breast cancer development. CONCLUSION: CCND1 may have a function in signalling pathways that control the proliferation of mammary epithelial cells.

A Novel Phytocolorant, Neoxanthin, as a Potent Chemopreventive: Current Progress and Future Prospects.

Cancer is a general term for a group of similar diseases. It is a combined process that results from an accumulation of abnormalities at different biological levels, which involves changes at both genetic and biochemical levels in the cells. Several modifiable risk factors for each type of cancer include heredity, age, and institutional screening guidelines, including colonoscopy, mammograms, prostate-specific antigen testing, etc., which an individual cannot modify. Although a wide range of resources is available for cancer drugs and developmental studies, the cases are supposed to increase by about 70% in the next two decades due to environmental factors commonly driven by the way of living. The drugs used in cancer prevention are not entirely safe, have potential side effects and are generally unsuitable owing to substantial monetary costs. Interventions during the initiation and progression of cancer can prevent, diminish, or stop the transformation of healthy cells on the way to malignancy. Diet modifications are one of the most promising lifestyle changes that can decrease the threat of cancer development by nearly 40%. Neoxanthin is a xanthophyll pigment found in many microalgae and macroalgae, having significant anti-cancer, antioxidant and chemo-preventive activity. In this review, we have focused on the anti-cancer activity of neoxanthin on different cell lines and its cancer-preventive activity concerning obesity and oxidative stress. In addition to this, the preclinical studies and future perspectives are also discussed in this review.

MiR-4486 inhibits colorectal cancer proliferation via targeting MAP2K4 to inhibit the activation of the p38MAPK/JNK signaling

ObjectiveSince MAP2K4 was reportedly involved in colorectal cancer development and the p38MAPK/JNK signaling transcription, this study aimed to investigate the mechanism by which the microRNA (miR)-4486 acts on colorectal cell proliferation. MethodsRT-PCR was conducted to measure the expression levels of the MAP2K4 and miR-4486 in NCM460, SW1116, and HCT116 cells. TargetScanHuman site anticipated that MAP2K4 may be a target of miR-4486. The dual-luciferase reporter assay confirmed their relationship. After plasmids of miR-4486 mimic and si-MAP2K4 transfection, MAP2K4 was quantified again, The CCK-8 assay was carried out to assess cell proliferation, while Scratch and Transwell assays were used to evaluate cell migration and invasion. Finally, miR-4486 mimic and SB203580 were applied in HCT116 and SW1116 cells separately or in combination. CCK-8, Scratch and Transwell assay were performed again. In addition, the proteins including c-capase3, Bax, Bcl2, MAP2K4, and the p38MAPK/JNK signaling-related proteins expression levels were quantified by Western blot (WB). ResultsCompared with the NCM460 cells, the expression level of MAP2K4 was elevated, while the expression level of miR-4486 was reduced in SW1116 and HCT116 cells. The results showed that elevated levels of miR-4486 suppressed cell proliferation, migration, and invasion in colorectal cells by downregulating MAP2K4 expression. miR-4486 mimic showed similar effects to SB203580, which promoted colorectal cell apoptosis and inhibited the p38 MAPK/JNK signaling transcription. ConclusionmiR-4486 may target MAP2K4 to inhibit colorectal cell proliferation by inhibiting the activation of the p38/JNK signaling pathway.

Identification of Necroptosis-related Molecular Subtypes and Construction of Necroptosis-related Gene Signature for Glioblastoma Multiforme.

Necroptosis is a highly regulated and genetically controlled process, and therefore, attention has been paid to the exact effects of this disorder on a variety of diseases, including cancer. An in-depth understanding of the key regulatory factors and molecular events that trigger necroptosis can not only identify patients at risk of cancer development but can also help to develop new treatment strategies. This study aimed to increase understanding of the complex role of necroptosis in glioblastoma multiforme (GBM) and provide a new perspective and reference for accurate prediction of clinical outcomes and gene-targeted therapy in patients with GBM. The objective of this study was to analyze the gene expression profile of necroptosis regulatory factors in glioblastoma multiforme (GBM) and establish a necroptosis regulatory factor-based GBM classification and prognostic gene signature to recognize the multifaceted impact of necroptosis on GBM. The necroptosis score of the glioblastoma multiforme (GBM) sample in TCGA was calculated by ssGSEA, and the correlation between each gene and the necroptosis score was calculated. Based on necroptosis score-related genes, unsupervised consensus clustering was employed to classify patients. The prognosis, tumor microenvironment (TME), genomic changes, biological signal pathways and gene expression differences among clusters were analyzed. The gene signature of GBM was constructed by Cox and LASSO regression analysis of differentially expressed genes (DEGs). Based on 34 necroptosis score-related genes, GBM was divided into two clusters with different overall survival (OS) and TME. A necroptosis-related gene signature (NRGS) containing 8 genes was developed, which could stratify the risk of GBM in both the training set and verification set and had good prognostic value. NRGS and age were both independent prognostic indicators of GBM, and a nomogram developed by the integration of both of them showed a better predictive effect than traditional clinical features. In this study, patients from public data sets were divided into two clusters and the unique TME and molecular characteristics of each cluster were described. Furthermore, an NRGS was constructed to effectively and independently predict the survival outcome of GBM, which provides some insights for the implementation of personalized precision medicine in clinical practice.

Discovery and Functional Characterization of a Potent, Selective, and Metabolically Stable PROTAC of the Protein Kinases DYRK1A and DYRK1B.

Small-molecule-induced protein degradation has emerged as a promising pharmacological modality for inactivating disease-relevant protein kinases. DYRK1A and DYRK1B are closely related protein kinases that are involved in pathological processes such as neurodegeneration, cancer development, and adaptive immune homeostasis. Herein, we report the development of the first DYRK1 proteolysis targeting chimeras (PROTACs) that combine a new ATP-competitive DYRK1 inhibitor with ligands for the E3 ubiquitin ligase component cereblon (CRBN) to induce ubiquitination and subsequent proteasomal degradation of DYRK1A and DYRK1B. The lead compound (DYR684) promoted fast, efficient, potent, and selective degradation of DYRK1A in cell-based assays. Interestingly, an enzymatically inactive splicing variant of DYRK1B (p65) resisted degradation. Compared to competitive kinase inhibition, targeted degradation of DYRK1 by DYR684 provided improved suppression of downstream signaling. Collectively, our results identify DYRKs as viable targets for PROTAC-mediated degradation and qualify DYR684 as a useful chemical probe for DYRK1A and DYRK1B.

The role of SIRT1 in autophagy and drug resistance: unveiling new targets and potential biomarkers in cancer therapy

Cancer, the world’s second leading cause of death after cardiovascular diseases, is characterized by hallmarks such as uncontrolled cell growth, metastasis, angiogenesis, hypoxia, and resistance to therapy. Autophagy, a cellular process that can both support and inhibit cancer progression, plays a critical role in cancer development and progression. This process involves the formation of autophagosomes that ultimately fuse with lysosomes to degrade cellular components. A key regulator of this process is Sirtuin 1 (SIRT1), which significantly influences autophagy. This review delves into the role of SIRT1 in modulating autophagy and its broader impacts on carcinogenesis. SIRT1 regulates crucial autophagy mediators, such as AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), effectively promoting or suppressing autophagy. Beyond its direct effects on autophagy, SIRT1’s regulatory actions extend to other cell death processes, including apoptosis and ferroptosis, thereby influencing tumor cell proliferation, metastasis, and chemotherapy responses. These insights underscore the complex interplay between SIRT1 and autophagy, with significant implications for cancer therapy. Targeting SIRT1 and its associated pathways presents a promising strategy to manipulate autophagy in cancer treatment. This review underscores the potential of SIRT1 as a therapeutic target, opening new avenues for enhancing cancer treatment efficacy.

LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway

BackgroundLong noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy.MethodsWe analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy.ResultsWe determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis.ConclusionsOur results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

Role of N6-methyladenosine methylation in head and neck cancer and its regulation of innate immune pathways

N6-methyladenosine (m6A) is considered the most prevalent methylation modification in messenger RNA (mRNA) that critically impacts head and neck cancer (HNC) pathogenesis and development. Alterations of m6A methylation related proteins are closely related to the progression, therapeutic effect, and prognosis of HNC. The human innate immune system activates immune pathways through pattern recognition receptors, which can not only resist pathogen infection, but also play a vital role in tumor immunity. Emerging evidence has confirmed that m6A methylation affects the activation of innate immune pathways such as TLR, cGAS-STING, and NLR by regulating RNA metabolism, revealing its potential mechanisms in the innate immune response of tumor cells. However, the relevant research is still in its infancy. This review elaborates the biological significance of RNA m6A methylation in HNC and discusses its potential regulatory relationship with TLR, cGAS-STING, and NLR pathways, providing a new perspective for in-depth understanding of the role of RNA methylation in the innate immune mechanism and therapeutic application of HNC.

Synergistic strategies for cancer treatment: leveraging natural products, drug repurposing and molecular targets for integrated therapy

Abstract Background Uncontrolled cell proliferation is a major cause of cancer development and progression. Inflammation along with inflammatory mediators and cells play a significant role in cancer. Cancer ranks in second in mortality rates, following cardiac diseases. Phytochemicals from medicinal plants offer a natural and effective approach for treating Inflammation and cancer. Main body of the abstract Animal studies provide evidence that phytochemicals present in food acts as antioxidants, anti-aging molecules, and health promoters, thereby extending lifespan. These natural compounds include quercetin, epicatechin, resveratrol, curcumin, kaempferol, vitamin C and carotenoids. However, clinical data on humans is still awaited. Conventional allopathic cancer therapies often have severe side effects. Recently, drug repurposing has emerged as an alternative strategy offering lower costs, shorter development times and the advantage of existing clinical data. The primary goal of drug repurposing is to discover new uses for approved or experimental drugs. Short conclusion The current review elucidates the side effects of synthetic drugs and the beneficial effects of phytochemicals and non-oncological drugs along with their mechanisms of action for treating cancer. Additionally, it highlights clinical trial data for various cancers focusing on molecular targets. By integrating natural products, drug repurposing and molecular targets, we can develop multifaceted therapies that maximize efficacy and minimize adverse effects. This integrated approach promises more personalized and effective treatments, improving patient outcomes and quality of life. Future research should identifying novel natural compounds, explore repurposing opportunities for existing drugs, and elucidate molecular targets for precise therapy. Additionally, clinical trials should be conducted to validate the efficacy and safety of these combined strategies in cancer patients. Graphical abstract

Construction of M2 macrophage-related gene signature for predicting prognosis and revealing different immunotherapy response in bladder cancer patients.

Bladder cancer development is closely associated with the dynamic interaction and communication between M2 macrophages and tumor cells. However, specific biomarkers for targeting M2 macrophages in immunotherapy remain limited and require further investigation. In this study, we identified key co-expressed genes in M2 macrophages and developed gene signatures to predict prognosis and immunotherapy response in patients. Public database provided the bioinformatics data used in the analysis. We created and verified an M2 macrophage-related gene signature in these datasets using Lasso-Cox analysis. The predictive value and immunological functions of our risk model were examined in bladder cancer patients, and 158 genes were found to be significantly positively correlated with M2 macrophages. Moreover, we identified two molecular subgroups of bladder cancer with markedly different immunological profiles and clinical prognoses. The five key risk genes identified in this model were validated, including CALU, ECM1, LRP1, CYTL1, and CCDC102B, demonstrating the model can accurately predict prognosis and identify unique responses to immunotherapy in patients with bladder cancer. In summary, we constructed and validated a five-gene signature related to M2 macrophages, which shows strong potential for forecasting bladder cancer prognosis and immunotherapy response.

Performance of somatic structural variant calling in lung cancer using Oxford Nanopore sequencing technology

BackgroundLung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and seven structural variant callers comprised of generic callers (SVIM, Sniffles2, DELLY in generic mode and cuteSV) and somatic callers (Severus, SAVANA, nanomonsv and DELLY in somatic modes).ResultsDifferent combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short-read sequencing. When compared to somatic structural variants detected with short-read sequencing, more events were detected with long-read sequencing. The mean recall of somatic variant events identified by long-read sequencing was higher for the somatic callers (72%) than generic callers (53%). Among the somatic callers when using the minimap2 aligner, SAVANA and Severus achieved the highest recall at 79.5% and 79.25% respectively, followed by nanomonsv with a recall of 72.5%.ConclusionLong-read sequencing can identify somatic structural variants in clincal samples. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.

Advantages of the zebrafish tumor xenograft model: the evaluation of efficacy in cancer therapy and the application to the study of lncRNAs

In the current preclinical anti-tumor researches, there is a general lack of an in vivo model that can quickly and efficiently screen effective anti-tumor drugs. As a species that is 87% genetically similar to humans, zebrafish have been widely used to model human diseases, and they are considered an alternative economic model for studying cancer development, proliferation, and metastasis. The zebrafish tumor xenograft model has been effectively used for cancer drug development at all levels, including target validation, and high-throughput screening of long non-coding RNAs (lncRNAs) that may be involved in tumor regulation. In this review, we provide a comprehensive overview of zebrafish as an in vivo model for cancer cell growth, migration, anti-tumor immunotherapy, and anti-tumor drug screening. In addition, the regulatory mechanisms of some active lncRNAs have been identified to play a role in the pathogenesis of cancer, but it is still necessary to take advantage of the efficient zebrafish model to screen and learn more about the role of these molecules in tumor development and migration. Current anti-tumor therapies are limited by severe toxicity and multidrug resistance. There is an urgent need for the cost-effective and efficient in vivo research tools to improve our understanding and overcome these problems. This paper reviews the different purposes of anti-tumor research using zebrafish model. We discuss the use of zebrafish in cancer cell proliferation and metastasis, identifying signaling pathways, cancer drug discovery and treatment development, and toxicity studies. Finally, this review highlights the limitations of the field and future directions to effectively utilize zebrafish as a highly efficient model for cancer treatment development.

Upregulation of Apoptosis Related Genes in Clinically Normal Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Effort to Maintain Tissue Homeostasis

PurposeThe field cancerization concept indicates the presence of pre-cancerous changes in clinically normal tissue surrounding the tumor. In squamous cell carcinoma of the oral tongue (SCCOT) which is infrequently linked to human papillomavirus infection, we have previously reported that clinically normal tongue contralateral to tumor (NTCT) is molecularly abnormal. Here, combining our transcriptomic and genomic data, we aimed to investigate the contribution of molecular changes in NTCT to cancer development.MethodsMicroarray gene expression data of 14 healthy controls, 23 NTCT and 29 SCCOT samples were investigated to characterize transcriptional profiles in NTCT. Whole exome sequencing and RNA-sequencing data of paired NTCT and tumor samples from 15 SCCOT patients were used to study correlation between copy number variation and differential gene expression.ResultsUsing supervised multivariate partial least squares discriminant analysis, a total of 61 mRNAs that distinguish NTCT from healthy tongue were selected. Functional enrichment analysis of the 22 upregulated genes showed increased “positive regulation of nitrogen compound metabolic process” in NTCT. All 12 genes involved in this process have roles in apoptosis (anti- and/or pro-apoptotic). Compared to healthy controls, Zinc Finger Protein 395 (ZNF395), a pro-apoptotic tumor suppressor located on chromosome 8p, was the only gene showing increased mRNA level in NTCT whereas decreased in SCCOT. Given the frequent loss of chromosome 8p in SCCOT, the impact of ZNF395 copy number variation on gene expression was further examined, revealing a positive correlation between copy number and mRNA level (correlation coefficient = 0.572, p < 0.001).ConclusionNTCT is susceptible to malignant transformation, where tissue homeostasis is maintained at least partly through regulation of apoptosis. Loss of the pro-apoptotic gene ZNF395 could thus initiate cancer development.

Association of ERCC1 Gene Polymorphisms (rs3212986 and rs11615) With the Risk of Lung Cancer in a Population From Southeast Iran

Background: Polymorphisms within the excision repair cross-complementation group 1 (ERCC1), an essential component of DNA repair mechanisms, have been associated with various malignancies. This study aimed to evaluate the association of the single-nucleotide polymorphisms (SNPs) rs3212986 and rs11615 within the ERCC1 gene in non-small cell lung cancer (NSCLC) patients. Study Design: A case-control study. Methods: Genomic DNA was extracted from the peripheral blood samples of 83 NSCLC patients and 119 healthy individuals. The genetic diversity of SNPs rs3212986 and rs11615 was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The RFLP results were confirmed through sequencing. Results: The TT genotype of the rs11615 SNP was associated with a higher risk of NSCLC development (odds ratio: 3.900, 95% confidence interval: 0.603, 22.866, P=0.050). Furthermore, the AA genotype of rs3212986 was related to a higher risk of NSCLC development (OR: 2.531, 95% CI: 1.017, 6.300, P=0.046). A significant association was observed between smoking and lung cancer (OR: 3.072, 95% CI: 1.715, 5.503, P&lt;0.001). Moreover, among non-smokers, there was an association between lung cancer risk and the AA (OR: 6.825, 95% CI: 1.722, 27.044, P=0.006) and AC (OR: 2.503, 95% CI: 0.977, 6.412, P=0.056) genotypes of rs3212986. However, no correlation was found between the genotypes of these SNPs and patients’ sensitivity to cisplatin and carboplatin (P ˃ 0.05). Conclusion: The rs11615-related TT genotype and the rs3212986-related AA genotype may be associated with a higher risk of lung cancer development.

A Literature Review of the Role of Candida albicans in the Occurrence and Development of Several Cancers

Candida albicans (C. albicans) is an opportunistic fungus that usually colonizes specific parts of the human body and tends to infect hosts with immunocompromised function, including cancer patients. Several studies have pointed to the direct or indirect involvement of (C. albicans) in oral, esophageal, gastric, pancreatic, colorectal, liver, breast, and skin cancers. So, this article reviews the relationship between C. albicans and various cancers and describes the mechanisms by which this fungus may be involved in the occurrence and development of these cancers. For this reason, keywords such as: "Candida," "cancer," "oral cancer," "esophageal cancer," "gastric cancer," "colorectal cancer," "pancreatic cancer," "liver cancer," "breast cancer," "skin cancer", "risk factors" and "epidemiology" were searched. Articles published in scientific databases, such as Google Scholar, PubMed/MEDLINE, Elsevier, and Scopus, were used. In these articles, it is mentioned that C. albicans may play a role in the occurrence and development of various cancers via several mechanisms, such as modulation of the immune system, induction of matrix metalloproteinases, over-expression of prognostic marker genes related to metastatic events, damaging mucosal epithelium, microbiome changes, activation of oncogenic signalling pathways, induction of chronic inflammation and production of carcinogenic metabolites including nitrosamine and acetaldehyde.

Circulating RKIP and pRKIP in Early-Stage Lung Cancer: Results from a Pilot Study

Background: Lung cancer (LC) is the leading cause of cancer-related deaths. Although low-dose computed tomography (LD-CT) reduces mortality, its clinical use is limited by cost, radiation, and false positives. Therefore, there is an urgent need for non-invasive and cost-effective biomarkers. The Raf Kinase Inhibitor Protein (RKIP) plays a crucial role in cancer development and progression and may also contribute to regulating the tumor–immune system axis. This protein has recently been described in biological fluids. Therefore, we conducted a pilot case–control study to assess RKIP and phosphorylated RKIP (pRKIP) levels in the urine and blood of LC patients. Methods: A novel enzyme linked immunosorbent assay (ELISA) assay was used to measure RKIP and pRKIP levels in urine and blood samples of two cohorts of LC patients and healthy controls (HSs). Furthermore, the biomarkers levels were correlated with tumor characteristics. Results: Serum, but not urine, levels of RKIP were significantly elevated in LC patients, distinguishing them from low- and high-risk healthy subjects with 93% and 74% accuracy, respectively. The RKIP/pRKIP ratio (RpR score) showed an accuracy of 90% and 79% in distinguishing LC patients from HS and HR-HS, respectively. Additionally, the RpR score correlated better with dimension, stage, and lymph node involvement in the tumor group. Conclusions: The serum RKIP and pRKIP profile may be a promising novel biomarker for early-stage LC.

Impact of the Lung Microbiota on Development and Progression of Lung Cancer

The past several years have provided a more profound understanding of the role of microbial species in the lung. The respiratory tract is a delicate ecosystem of bacteria, fungi, parasites, and viruses. Detecting microbial DNA, pathogen-associated molecular patterns (PAMPs), and metabolites in sputum is poised to revolutionize the early diagnosis of lung cancer. The longitudinal monitoring of the lung microbiome holds the potential to predict treatment response and side effects, enabling more personalized and effective treatment options. However, most studies into the lung microbiota have been observational and have not adequately considered the impact of dietary intake and air pollutants. This gap makes it challenging to establish a direct causal relationship between environmental exposure, changes in the composition of the microbiota, lung carcinogenesis, and tumor progression. A holistic understanding of the lung microbiota that considers both diet and air pollutants may pave the way to improved prevention and management strategies for lung cancer.

Potential functions and mechanisms of lysine crotonylation modification (Kcr) in tumorigenesis and lymphatic metastasis of papillary thyroid cancer (PTC).

To examine the putative functions and mechanisms of lysine crotonylation (Kcr) during the development and progression of papillary thyroid cancer (PTC). Samples of thyroid cancer tissues were collected and subjected to liquid chromatography-tandem mass spectrometry. Crotonylated differentially expressed proteins (DEPs) and differentially expressed Kcr sites (DEKSs) were analyzed by Motif, dynamic expression model analysis (Mfuzz), subcellular localization, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, Go Ontology (GO) annotation, and protein-protein interaction analysis (PPI). Validation was performed by immunohistochemistry (IHC). A total of 262 crotonylated DEPs and 702 DEKSs were quantitated. First, for the tumor/normal comparison, a dynamic expression model analysis (Mfuzz) of the DEKSs revealed that clusters 1, 3, and 4 increased with the progression of thyroid cancer; however, cluster 6 showed a dramatic increase during the transition from N0-tumor to N1-tumor. Furthermore, based on GO annotation, KEGG, and PPI, the crotonylated DEPs were primarily enriched in the PI3K-Akt signaling pathway, Cell cycle, and Hippo signaling pathway. Of note, crosstalk between the proteome and Kcr proteome suggested a differential changing trend, which was enriched in Thyroid hormone synthesis, Pyruvate metabolism, TCA cycle, Cell cycle, and Apoptosis pathways. Similarly, for the LNM comparison group, the DEKSs and related DEPs were primarily enriched in Hydrogen peroxide catabolic process and Tight junction pathway. Finally, according to The Cancer Genome Atlas Program (TCGA) database, the differential expression of Kcr DEPs were associated with the prognosis of thyroid cancer, indicating the prognostic significance of these proteins. Moreover, based on the clinical validation of 47 additional samples, Kcr was highly expressed in thyroid tumor tissues compared with normal tissue (t = 9.792, P < 0.001). In addition, a positive correlation was observed between Kcr and N-cadherin (r = 0.5710, P = 0.0015). Moreover, N-cadherin expression was higher in the relatively high Kcr expression group (χ2 = 18.966, P < 0.001). Higher Kcr expression was correlated with thyroid tumorigenesis and lymphatic metastasis, which may regulate thyroid cancer progression by Pyruvate metabolism, TCA cycle, Cell cycle, and other pathways.