Synthetic Routes and Clinical Application of Representative Small-Molecule EGFR Inhibitors for Cancer Therapy.

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors.

METTL14 promotes neuroblastoma formation by inhibiting YWHAH via an m6A-YTHDF1-dependent mechanism.

Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5' UTR, were specifically recognized by the m6A "reader" protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

Synthesis of hierarchical mordenite by solvent-free method for dimethyl ether carbonylation reaction.

A series of hierarchical mordenite (MOR) catalysts were synthesized by adding soft templates via the solvent-free method. The influence of different kinds of soft templates on the structure, morphology and acid sites of mordenite were systematically characterized. The characterization results revealed that the addition of soft templates could successfully introduce hierarchical structure into the system while maintaining good crystallinity. The specific surface area and pore volume became larger. Surfactants could also affect the amount and distribution of acid sites, which in turn would affect the dimethyl ether carbonylation activity. Compared with cationic and nonionic surfactants, the addition of anionic surfactants such as sodium dodecyl benzene sulfonate could result in more Al species to preferentially enter into the 8 member ring, thus enhancing the amount of active sites for the carbonylation reaction while weakening the strength. Meanwhile, the addition of sodium dodecyl benzene sulfonate could also reduce the number of strong acid sites in the 12 member ring and obviously improve the carbonylation performance.

Identification of potential biomarkers in the peripheral blood of neonates with bronchopulmonary dysplasia using WGCNA and machine learning algorithms.

Bronchopulmonary dysplasia (BPD) is often seen as a pulmonary complication of extreme preterm birth, resulting in persistent respiratory symptoms and diminished lung function. Unfortunately, current diagnostic and treatment options for this condition are insufficient. Hence, this study aimed to identify potential biomarkers in the peripheral blood of neonates affected by BPD. The Gene Expression Omnibus provided the expression dataset GSE32472 for BPD. Initially, using this database, we identified differentially expressed genes (DEGs) in GSE32472. Subsequently, we conducted gene set enrichment analysis on the DEGs and employed weighted gene co-expression network analysis (WGCNA) to screen the most relevant modules for BPD. We then mapped the DEGs to the WGCNA module genes, resulting in a gene intersection. We conducted detailed functional enrichment analyses on these overlapping genes. To identify hub genes, we used 3 machine learning algorithms, including SVM-RFE, LASSO, and Random Forest. We constructed a diagnostic nomogram model for predicting BPD based on the hub genes. Additionally, we carried out transcription factor analysis to predict the regulatory mechanisms and identify drugs associated with these biomarkers. We used differential analysis to obtain 470 DEGs and conducted WGCNA analysis to identify 1351 significant genes. The intersection of these 2 approaches yielded 273 common genes. Using machine learning algorithms, we identified CYYR1, GALNT14, and OLAH as potential biomarkers for BPD. Moreover, we predicted flunisolide, budesonide, and beclomethasone as potential anti-BPD drugs. The genes CYYR1, GALNT14, and OLAH have the potential to serve as diagnostic biomarkers for BPD. This may prove beneficial in clinical diagnosis and prevention of BPD.

Synthesis and clinical application of new drugs approved by FDA in 2023.

In 2023, the U.S. Food and Drug Administration (FDA) granted approval to a total of 55 new drugs, comprising 29 new chemical entities (NCEs) and 25 new biological entities (NBEs). These drugs primarily focus on oncology, the central nervous system, anti-infection, hematology, cardiovascular, ophthalmology, immunomodulatory and other therapeutic areas. Out of the 55 drugs, 33 (60 %) underwent an accelerated review process and received approval, while 25 (45 %) were specifically approved for the treatment of rare diseases. The purpose of this review is to provide an overview of the clinical uses and production techniques of 29 newly FDA-approved NCEs in 2023. Our intention is to offer a comprehensive understanding of the synthetic approaches employed in the creation of these drug molecules, with the aim of inspiring the development of novel, efficient, and applicable synthetic methodologies.

Harmonizing the craft of crafting clinically endorsed small-molecule BCR-ABL tyrosine kinase inhibitors for the treatment of hematological malignancies.

The advancement and practical use of small-molecule tyrosine kinase inhibitors (TKIs) that specifically target the BCR-ABL fusion protein have introduced a revolutionary era of precision medicine for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This review offers a comprehensive exploration of the synthesis, mechanisms of action, and clinical implementation of clinically validated TKIs in the context of BCR-ABL, emphasizing the remarkable strides made in achieving therapeutic precision. We delve into the intricate design and synthesis of these small molecules, highlighting the synthetic strategies and modifications that have led to increased selectivity, enhanced binding affinities, and reduced off-target effects. Additionally, we discuss the structural biology of BCR-ABL inhibition and how it informs drug design. The success of these compounds in inhibiting aberrant kinase activity is a testament to the meticulous refinement of the synthetic process. Furthermore, this review provides a detailed analysis of the clinical applications of these TKIs, covering not only their efficacy in achieving deep molecular responses but also their impact on patient outcomes, safety profiles, and resistance mechanisms. We explore ongoing research efforts to overcome resistance and enhance the therapeutic potential of these agents. In conclusion, the synthesis and utilization of clinically validated small-molecule TKIs targeting BCR-ABL exemplify the transformative power of precision medicine in the treatment of hematological malignancies. This review highlights the evolving landscape of BCR-ABL inhibition and underscores the continuous commitment to refining and expanding the therapeutic repertoire for these devastating diseases.

Progress in the application of dual-energy CT in pancreatic diseases.

Pancreatic diseases are difficult to diagnose due to their insidious onset and complex pathophysiological developmental characteristics. In recent years, dual-energy computed tomography (DECT) imaging technology has rapidly advanced. DECT can quantitatively extract and analyze medical imaging features and establish a correlation between these features and clinical results. This feature enables the adoption of more modern and accurate clinical diagnosis and treatment strategies for patients with pancreatic diseases so as to achieve the goal of non-invasive, low-cost, and personalized treatment. The purpose of this review is to elaborate on the application of DECT for the diagnosis, biological characterization, and prediction of the survival of patients with pancreatic diseases (including pancreatitis, pancreatic cancer, pancreatic cystic tumor, pancreatic neuroendocrine tumor, and pancreatic injury) and to summarize its current limitations and future research prospects.

Change in onset age of first primary colorectal cancer in the USA.

PURPOSE: Identifying the onset age of cancer is essential for its early intervention. The aim of this study was to characterize the features and investigate the variation tendency of first primary colorectal cancer (CRC) onset age in the USA. METHODS: For this retrospective population-based cohort analysis, data on patients diagnosed with first primary CRC (n = 330,977) between 1992 and 2017 were obtained from the Surveillance, Epidemiology, and End Results dataset. Annual percent changes (APC) and average APCs were calculated to examine the changes in average age at CRC diagnosis using the Joinpoint Regression Program. RESULTS: From 1992 to 2017, the average age at CRC diagnosis decreased from 67.0 to 61.2 years, declining by 0.22% and 0.45% annually before and after 2000. The age at diagnosis was lower in the distal than in the proximal CRC cases and the age has the downward trends in all subgroups of sex, race, and stage. Over one-fifth of CRC patients were initially diagnosed with distantly metastatic CRC, with the age lower than that in localized CRC cases (63.5 vs 64.8 years). CONCLUSIONS: The first primary CRC onset age has decreased significantly in the USA over the last 25 years and the modern lifestyle may be responsible for the decline. Specifically, the age of proximal CRC is invariably higher than that of distal CRC. Moreover, the age of advanced stage is lower than that of the early stage. Clinicians should adopt earlier screening age and more effective screening techniques for CRC.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

Suppression of endoplasmic reticulum stress-dependent autophagy enhances cynaropicrin-induced apoptosis via attenuation of the P62/Keap1/Nrf2 pathways in neuroblastoma.

Autophagy has dual roles in cancer, resulting in cellular adaptation to promote either cell survival or cell death. Modulating autophagy can enhance the cytotoxicity of many chemotherapeutic and targeted drugs and is increasingly considered to be a promising cancer treatment approach. Cynaropicrin (CYN) is a natural compound that was isolated from an edible plant (artichoke). Previous studies have shown that CYN exhibits antitumor effects in several cancer cell lines. However, it anticancer effects against neuroblastoma (NB) and the underlying mechanisms have not yet been investigated. More specifically, the regulation of autophagy in NB cells by CYN has never been reported before. In this study, we demonstrated that CYN induced apoptosis and protective autophagy. Further mechanistic studies suggested that ER stress-induced autophagy inhibited apoptosis by activating the p62/Keap1/Nrf2 pathways. Finally, in vivo data showed that CYN inhibited tumour growth in xenografted nude mice. Overall, our findings suggested that CYN may be a promising candidate for the treatment of NB, and the combination of pharmacological inhibitors of autophagy may hold novel therapeutic potential for the treatment of NB. Our paper will contribute to the rational utility and pharmacological studies of CYN in future anticancer research.

Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

BACKGROUND: Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. RESULTS: We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. CONCLUSION: INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.

Dietary supplementation with metformin improves testis function and semen quality and increases antioxidants and autophagy capacity in goats.

ATP is essential for mammalian sperm to maintain fertilizing capacity. Metformin (Met) can activate 5'-AMP-activated protein kinase (AMPK) to maintain energy homeostasis. Thus, the aim of the present study was to investigate whether Met can improve testis function, semen quality, antioxidant and autophagy capacity through AMPK mediation of energy metabolism in goats. Twelve adult goats were randomly divided into three dietary treatments. All goats were fed a basal diet for 3 weeks and then assigned to a Met supplementation diet containing 0, 150, or 300 mg/kg for 8 weeks. The results showed that sperm viability, sperm membranal functional integrity, and acrosome integrity increased (P < 0.05) relative to the other treatments in the 300 mg/kg Met group. Growth hormone (GH) and insulin-like growth factor (IGF-1) in the 300 mg/kg Met group significantly decreased (P < 0.05) relative to the control group. Estrogen levels (E2) in the 300 mg/kg Met group remarkably improved (P < 0.05) compared with the control group. The activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) significantly increased (P < 0.05) in the 300 mg/kg Met group relative to the control group. A significant increase in AMPK and p-AMPK protein expression in the 300 mg/kg Met group was observed relative to the control group (P < 0.05). Belicin-1 and LC3II/I protein expression was significantly increased by adding Met to the diet (P < 0.05) and reached a maximum in the 300 mg/kg Met group. In addition, differentially expressed genes (DEGs) of goat testis were confirmed by RNA-seq. GO enrichment analysis revealed that DEGs were enriched in testicular metabolism and sperm development-related functional pathways. Overall, the results indicate that Met may play an important role in the regulation of testis function, semen quality, antioxidant, and autophagy capacity. These findings will help elucidate the role of Met in goat testis development.

Endoscopic excision as a viable alternative to major resection for early duodenal cancers: A population-based cohort study.

BACKGROUND: Duodenal cancer presents an elusive therapeutic challenge for clinicians to treat because of its highly malignant behavior and anatomical complexity. Endoscopic excision has been administered to treat early-stage cancers of upper gastrointestinal tract, especially esophagus and stomach cancer. There is currently a scarcity of data regarding the application and efficacy of endoscopic resection for early duodenal cancer due to its rarity. This study aimed at exploring the prevalence and efficacy of endoscopic excision in treatment for early duodenal cancer in comparison with major surgery. METHODS: This cohort study retrospectively collected patients with primary Tis/T1-N0-M0 duodenal cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2017. Prevalence of endoscopic excision in duodenal cancer treatment, overall survival (OS) and disease-specific survival (DSS) of patients who received different tumor-resection procedures were estimated. RESULTS: A total of 1354 patients with Tis/T1-stage duodenal cancer were identified. Most patients (69.4%) underwent tumor resection as initial treatments. Among them, 65.7% underwent endoscopic excision, while 34.3% underwent major surgery. The multivariable Cox analyses revealed that endoscopic excision was associated with a significantly favorable OS (HR: 0.70; 95% CI: 0.52-0.95, p = 0.02) and DSS (HR: 0.32; 95% CI: 0.17-0.60, p < 0.001), compared to major surgery, for Tis/T1-stage cancer patients. In addition to cancer-related deaths (p < 0.001), endoscopic resection manifested significantly lower cumulative mortality rate of post-operative infectious diseases (p = 0.03). CONCLUSION: Endoscopic resection currently accounted for approximately two-thirds of all procedures to resect Tis/T1-stage duodenal tumor. Endoscopic resection represents a viable therapeutic option in the management of Tis/T1-stage duodenal cancer for its oncological superiorities to major surgery and its capacity to reduce operative traumas and morbidities.

Millefeuille-inspired highly conducting polymer nanocomposites based on controllable layer-by-layer assembly strategy for durable and stable electromagnetic interference shielding.

High-performance conductive polymer nanocomposites containing two-dimensional (2D) MXene are garnering substantial interest for electromagnetic shielding interference (EMI) in flexible electronics. However, owing to the non-sticky nature and undesirable mechanical performances of freestanding MXene film, it remains a formidable challenge to make the trade-off between outstanding EMI shielding capability and high stability. In this study, inspired by the structure and manufacturing process of millefeuille cakes, we propose a controllably layer-by-layer assembling strategy for fabricating flexible multilayered EMI shielding composite films based on MXene and an inherently conductive polymer (ICP). The multilayer films bearing alternating aramid nanofibers/polypyrrole nanowires (AFPy) and Ti3C2Tx reinforced by waterborne polyurethane (Ti3C2Tx@WPU) layers are orderly constructed by a facile alternating vacuum filtration method. Benefiting from the special architectures, the AFPy-70/Ti3C2Tx@WPU-4 film exhibits a high electrical conductivity of 1.74 S cm-1 and superior EMI shielding effectiveness of 40.9 dB at lower Ti3C2Tx loading content (32 wt%). Moreover, synergistic integration of hydrogen bonding and π-π stacks in multilayered films is achieved, especially in tandem with controlled crack generation within the whole film. Excellent EMI shielding performance remains well maintained even after being suffered to back-and-forth bending test (over 10,000 cycles), ultrasonication, and cryogenic temperature, validating great potential as high-performance EMI shielding film resisting extreme conditions.

BRD4 inhibitor GNE987 exerts anti-cancer effects by targeting super-enhancers in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB. RESULTS: In this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated with MYC and the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript, FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data. FAM163A is abnormally transcribed by SEs, playing an important role in NB occurrence and development. CONCLUSION: GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.

Variation of TNF modulates cellular immunity of gregarious and solitary locusts against fungal pathogen Metarhizium anisopliae.

Changes in population density lead to phenotypic differentiation of solitary and gregarious locusts, which display different resistance to fungal pathogens; however, how to regulate their cellular immune strategies remains unknown. Here, our stochastic simulation of pathogen proliferation suggested that humoral defense always enhanced resistance to fungal pathogens, while phagocytosis sometimes reduced defense against pathogens. Further experimental data proved that gregarious locusts had significantly decreased phagocytosis of hemocytes compared to solitary locusts. Additionally, transcriptional analysis showed that gregarious locusts promoted immune effector expression (gnbp1 and dfp) and reduced phagocytic gene expression (eater) and the cytokine tumor necrosis factor (TNF). Interestingly, higher expression of the cytokine TNF in solitary locusts simultaneously promoted eater expression and inhibited gnbp1 and dfp expression. Moreover, inhibition of TNF increased the survival of solitary locusts, and injection of TNF decreased the survival of gregarious locusts after fungal infection. Therefore, our results indicate that the alerted expression of TNF regulated the immune strategy of locusts to adapt to environmental changes.

Incidence and characteristics of death from peptic ulcer among cancer patients in the United States.

Most cancer patients die of non-cancer causes, and peptic ulcer is one cause that deserves attention. To characterize the incidence and risk factors of death from peptic ulcer among cancer patients, we extracted the data of cancer patients registered in the Surveillance Epidemiology and End Results (SEER) program from 1975 to 2016. Out of the 8,471,051 patients extracted from SEER, 4,698 died from peptic ulcer, with a mortality rate of 9.08/100,000 person-years. Meanwhile, the mortality rate in the general population was 5.09/100,000 person-years, giving a standardized mortality ratio (SMR) of 1.78 (95% confidence interval, 1.73-1.84). Patients who are female, of other race, unmarried, and with distant tumor stage have greater SMRs. A higher SMR was associated with a younger age at diagnosis. Among those aged < 40 years at diagnosis, the plurality of fatal peptic ulcers occurred in patients with leukemia and lymphoma, while in patients aged > 40 years, the majority occurred in those with prostate, breast, colorectum, and lung cancer. Patients with upper digestive system malignancies had the highest SMRs and hazard ratios (HRs), which could be ascribed to radiotherapy-induced damage to the gastroduodenum. The risk declined rapidly one year after diagnosis. However, the SMRs in the upper digestive system cancer survivors increased significantly over ten years after diagnosis. Upper digestive system cancers adjacent to the gastroduodenum were associated with higher SMRs and HRs compared with other types of cancer, possibly contributing partially to the damage caused by radiotherapy on the radiosensitive gastroduodenum.

Incidence of suicide among adolescent and young adult cancer patients: a population-based study.

BACKGROUND: As the survival rates of cancer patients continue to increase, most cancer patients now die of non-cancer causes. Several studies have been showing elevated suicide rates among patients with cancer. However, no large-scale study has thoroughly assessed the risk of suicide among adolescent and young adult (AYA) patients with cancer. This study was conducted to characterize suicide mortality among AYA patients in the US and identify risk factors associated with a higher risk of suicide. METHODS: Patients aged 15-39 years were residents of the US served by the Surveillance, Epidemiology, and End Results (SEER) program, who were diagnosed with cancers from 1973 to 2015. RESULTS: We report that 981 of the 572,500 AYA patients with cancer committed suicide, for an age-, sex-, and race-adjusted suicide rate of 17.68/100,000 person-years. The rate of suicide was 14.33/100,000 person-years in the corresponding general population, giving a standardized mortality ratio (SMR) of 1.234 [95% confidence interval (CI) 1.159-1.313]. Higher suicide rates were associated with male sex, white race, unmarried state, distant tumor stage, and single primary tumor. AYA patients with otorhinolaryngologic, gonad, stomach, soft tissue, and nasopharyngeal cancer were at the greatest risk of suicide compared with those with other types of cancer. In older patients (≥ 40 years), the risk was highest in those with lung, stomach, oral cavity and pharynx, larynx, and bone malignancies. SMRs were highest in the first 5 years after diagnosis for most types of cancer. CONCLUSION: AYA patients with cancer in the US have over 20% higher the incidence of suicide of the general population, and most suicides occurred in the first 5 years following diagnosis. Suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of these young patients with cancer, particularly that of those with certain types of cancer, is warranted.

Prognostic Value of Inflammatory Markers in Nasopharyngeal Carcinoma Patients in the Intensity-Modulated Radiotherapy Era.

PURPOSE: Inflammatory markers have been widely used in various cancers, but rarely in nasopharyngeal carcinoma (NPC). Here, we evaluated the prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte-ratio (PLR), systemic immune index (SII), and systemic inflammation response index (SIRI) on NPC in the intensity-modulated radiotherapy (IMRT) era. METHODS: We retrospectively analyzed data from NPC patients from the Renmin Hospital of Wuhan University, between January 2012 and July 2020. We used Chi-square test or Fisher's exact test to compare the baseline characteristics, then applied Kaplan-Meier (K-M) survival analysis to compare the overall survival (OS) and progression-free survival (PFS) rates. Multivariate Cox proportional risk models were applied to identify independent prognostic factors. RESULTS: We enrolled a total of 342 NPC patients and found optimal cut-off values of 2.65, 184.91, 804.08, and 1.34 for NLR, PLR, SII, and SIRI, respectively. K-M survival analysis revealed that high NLR, PLR, SII, and SIRI were significantly associated with worse OS and PFS relative to those in the low groups. Results from univariate Cox analysis showed that clinical, T, and M stages, as well as NLR, PLR, SII, and SIRI were associated with OS, whereas age, alongside the aforementioned parameters, was associated with PFS. Moreover, multivariate Cox analysis showed that age ≥49 years (HR=2.48, 95% CI=1.21-5.05, P=0.013) and M1 stage (HR=3.84, 95% CI=1.52-9.73, P=0.013) were independent prognostic factors for OS, whereas SIRI ≥1.34 (HR=1.91, 95% CI=1.05-3.47, P=0.034) and M1 stage (HR=2.91, 95% CI=1.44-5.86, P=0.003) were independent prognostic factors for PFS. CONCLUSION: Overall, our findings indicated that high NLR, PLR, SII, and SIRI were significantly associated with poor OS and PFS in NPC patients. High SIRI may be an independent risk factor for PFS of NPC patients in the IMRT era.