Recent cancer treatment development has focused on smart drugs, primarily using nanomaterials as carriers. However, concerns about nanomaterial fate and body clearance have led to exploring alternative approaches. This study presents a novel targeted smart drug that uses normal lymphocytic cells as carriers and exploits cancer microenvironment characteristics for drug release, avoiding systemic damage. The research investigated a complex combining gracillin (natural carrier) and the chemotherapeutic agent 5-bromouracil (5-BrU). Molecular docking showed the 5BrU-G complex had superior binding affinity (- 7.96 kcal mol-1) to glycosylated adhesion domain of human T lymphocyte glycoprotein CD2 (1CDB) cell surface receptors in silico. The complex was successfully synthesized through double replacement, precipitation, and neutralization reactions, confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cytotoxic and genotoxic studies revealed the selectivity of 5BrU-G against cancer cells (MDA-MB-231 and Caco-2) while saving normal cells (MCF-10A and CCD 841 CoN). Unlike 5-BrU alone, which showed significant genotoxicity in normal cells, the 5BrU-G complex demonstrated minimal toxic effects. The selective targeting mechanism of 5BrU-G relies on APOBEC3 enzyme activity, which is elevated in cancer cells but is absent in normal cells. This was confirmed when APOBEC3 inhibition prevented the complex's cancer-killing activity. This novel approach offers promising alternatives for improving cancer therapy efficacy while reducing side effects.

Patients with metastatic malignant melanoma have a survival rate of less than one year. Nivolumab, a monoclonal antibody against programmed cell death 1 (PD-1) receptor, has improved survival in patients without BRAF mutations. The HALP score, calculated from hemoglobin, albumin, lymphocyte, and platelet levels, provides information about a patient immune and nutritional status. High HALP scores have been associated with a better prognosis in various cancers. This study aimed to investigate the effect of high HALP scores on response to nivolumab treatment in patients with metastatic malignant melanoma. A retrospective study was conducted on 44 patients with metastatic malignant melanoma treated with nivolumab at Adana City Training and Research Hospital between 2014 and 2021. Patients who received dabrafenib-trametinib before nivolumab treatment were excluded. The HALP scores were calculated using laboratory parameters before the first nivolumab treatment. Statistical analyses were performed using SPSS version 25.0. The study included 22 female and 22 male patients with a mean age of 61.4 ± 15.6 years. Of the patients, 10 (27.2%) had a positive BRAF mutation, whereas 34 (77.3%) did not. The HALP score cutoff value was determined as 30.1. Patients with high HALP scores had significantly longer progression-free survival (PFS) and overall survival (OS) compared to those with low HALP scores (PFS: median 5.8 vs 3.1 months, P = .041; OS: median 54.9 vs 14.4 months, P = .005). In this study, we found that high HALP scores were significantly associated with longer PFS and OS in metastatic malignant melanoma patients receiving nivolumab treatment. HALP score was associated with both PFS and OS in patients with metastatic malignant melanoma treated with nivolumab. This immuno-nutritional parameter may be useful in various cancers; however, further prospective studies with larger patient cohorts are needed for clinical application.

Malignant tumors of minor salivary glands (MGSTs) are rare and exhibit significant heterogeneity in terms of etiology, histology and prognosis.

This retrospective analysis of 48 resected MGSTs employed Receiver Operating Characteristic (ROC) curves and logistic regression models to evaluate the association between the systemic inflammatory response index (SIRI), the systemic immuno-inflammation index (SII), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) with overall survival (OS). Although these biomarkers showed some correlation with OS, none were statistically significant when considered individually.

Significant correlation was observed between the SIRI, SII, and NLR with overall survival (OS). Among these, SIRI was the most reliable predictor, with an area under the curve (AUC) of 0.713, 80% sensitivity, and 70% specificity.

While these inflammatory biomarkers correlate with the prognosis and risk stratification of MGSTs, there is currently no clinical utility in decision making due to the lack of standardization and their limited application in clinical practice.

Characterization of the tumor immune microenvironment (TIME) of pituitary neuroendocrine tumors (PitNETs) is crucial for understanding the behavior of different types of PitNETs and identification of possible causes of their aggressiveness, rapid growth, and resistance to therapy. High-dimensional flow cytometry (FC) is a promising technology for studying TIME but poses unique technical challenges, especially when applied to solid tissues and PitNETs, in particular. This paper evaluates the potential of FC for analyzing TIME in PitNETs by addressing methodological difficulties across all stages of the workflow and proposing solutions. We developed a protocol for preparing single-cell suspensions from PitNET tissues for FC. This involved optimization of enzymatic digestion and comparison of it with mechanical tissue dissociation assessing cell yield, viability, and target antigen expression. We designed four multicolor FC panels to analyze major lymphocyte and myeloid cell subsets including determination of subpopulations of T, B, NK cells and their activation and cytotoxic potential, neutrophils, monocytes, CD68 + CD64 + CD11blow macrophages of M2 and M1 subtypes, and two types of myeloid suppressor cells - PMN-MDSC and M-MDSC. Principles of multicolor panel design, spreading error, and importance of voltage balance for proper flow cytometer setting are discussed. The panels were validated and demonstrated the feasibility of their simultaneous use on pituitary tumor surgical tissue for comprehensive TIME characterization. We compared lymphocyte frequencies in blood, PitNETs, and three sequential PitNET eluates to find out the contamination level of PitNET samples with blood leukocytes. To address technical challenges, we propose a strategy of logical data gating that removes spurious signals from aggregates, dead cells, and subcellular debris that can interfere with analysis. Our results indicate that despite all technical difficulties, multiparametric FC can effectively characterize different types of PitNETs. This enhanced understanding of the immune infiltrate provides valuable insights into PitNET biology and advances clinical diagnostics.

Oral cavity carcinomas (OCCs) represent roughly 50% of all head and neck cancers. The risk of occult neck metastases for early-stage OCCs ranges from 15 to 35%, thus the need to develop tools that can support the diagnosis detecting these neck metastases. Inflammatory biomarkers and perineural and lympho-vascular invasion are emerging as effective in this field. The aim of this study is to demonstrate the effectiveness of these parameters to detect occult neck metastases in early-stage (T1-T2/N0) OCCs.

A retrospective analysis was conducted on 81 patients surgically treated for early-stage OCC. For all patients, data regarding TNM, pN status after the histopathological examination, inflammatory biomarkers, and perineural and lympho-vascular invasion have been obtained. A statistical analysis was performed using the receiver operating characteristic (ROC) curve to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR.

Fifty-eight patients confirmed N0 status after surgery, while twenty-three resulted pN+. The best cut-off to detect occult neck metastases were PLR 249.30, NLR 13.10, MLR 0.439, SII 1043.12, and SIRI 1.85. The accuracy to detect occult neck metastases was PLR 75%, NLR 81%, MLR 74%, SII 73%, SIRI 70%, perineural invasion 70%, and lympho-vascular invasion 83%.

Our results confirm that inflammatory biomarkers and perineural and lympho-vascular invasion are effective in detecting occult neck metastases in early-stage OCCs. The clinical relevance of this study is that these parameters could be used routinely as preoperative tools to support diagnosis and to help surgeons in the decision-making process, particularly regarding surgical indications for neck lymph nodes treatment.

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common disease that can cause occult metastasis (OM). Methods: This study aims to investigate the role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) in predicting the presence of neck OM in early-stage OTSCC. We reprocessed the pre-treatment blood data to calculate the NLR and the PLR on patients treated for OTSCC. We used a logistic regression model and the ROC curve to estimate the probability of metastases in cervical lymph nodes using data from pre-surgery blood tests. Results: During the period under review, 113 patients were treated for OTSCC; however, only 74 met the inclusion criteria and were, therefore, enrolled in the study. Twenty-five patients (35.3%) had lymph node metastases, and 46 (64.7%) did not. Without the NLR influence, the probability of metastasis is less than 50% (β0 = -1.058). A higher NLR value means a higher chance of metastasis. This is shown by the positive value of the NLR level coefficient (β1 = 0.135) and the ROC curve (AUC = 0.83). Conclusions: Our study showed a statistical correlation between high pre-treatment NLR values and neck OM in patients with OTSCC. These results may help to identify which patients are at risk of developing OM and then choose the right treatment.

The effect of the controlling nutritional status (CONUT) score on forecasting multiple myeloma (MM) prognosis is previously analyzed, whereas the results remained inconsistent. The present meta-analysis focused on identifying the exact function of CONUT in forecasting MM prognosis.

Web of Science, PubMed, Embase, CNKI, and Cochrane Library were comprehensively searched between inception and 1 February 2025. The effect of CONUT on forecasting MM overall survival (OS) and progression-free survival (PFS) was determined by computing pooled hazard ratios (HRs) together with 95% confidence intervals (CIs).

There were nine studies with 1,176 patients being recruited into the present work. As indicated by our pooled data, elevated CONUT was related to the dismal OS (HR = 1.87, 95% CI = 1.37-2.54, p < 0.001) of patients with MM. Nonetheless, CONUT was not significantly related to PFS (HR = 1.33, 95% CI = 0.81-2.19, p = 0.254) of MM. Furthermore, higher CONUT score showed a significant relationship to bone marrow plasma cells >30% (OR = 2.30, 95% CI = 1.32-3.99, p = 0.003). On the other hand, CONUT was not markedly correlated with gender (OR = 2.68, 95% CI = 0.81-8.82, p = 0.105), ISS stage (OR = 1.28, 95% CI = 0.94-1.75, p = 0.119), or ECOG PS (OR = 1.30, 95% CI = 0.84-2.01, p = 0.234) of MM.

Collectively, according to our results in this meta-analysis, higher CONUT score is markedly related to dismal OS, but not PFS in patients with MM. CONUT score can be used as a candidate marker used to predict MM prognosis in the clinic in the future.

Background/Objectives: Malignant carcinomas of the salivary glands account for approximately 1 to 7% of all head and neck malignancies and approximately 0.3% of all malignant neoplasms. Recently, the scientific community has focused on finding biomarkers that could tailor the treatment for patients with this type of cancer. The neutrophil-lymphocyte ratio (NLR) was the first marker studied and it is one of the most widely used; the platelet-lymphocyte ratio (PLR), the systemic immune inflammation index (SII) and the systemic inflammatory response index (SIRI) have recently emerged as important biomarkers. The aim of this scoping review is to evaluate the role of inflammatory biomarkers in the management of salivary gland malignancies. Methods: A review of the English literature on inflammatory blood markers in major salivary gland cancer was performed using PubMed, Scopus, and Google Scholar databases. The literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for scoping reviews. Results: Eleven full-text articles were included in this review, for a total of 1356 patients in which the role of inflammatory biomarkers (NLR, PLR, SII or SIRI) for the diagnosis and prognosis of salivary gland cancer was assessed. NLR (i) was evaluated in all the studies; (ii) it contributed to the diagnosis and prognosis of both adult and pediatric patients and (iii) can be considered the main biomarker, even if a universal cut-off range is not available yet. PLR, SII and SIRI were introduced more recently and were evaluated only in some studies. Conclusions: The findings of this study suggest that elevated NLR values, regardless of age, are more frequently associated with malignancy and a poor prognosis. Further studies are necessary to evaluate the role of biomarkers other than NLR, and to identify universal and practical cut-off values.

Chemoradiotherapy (CRT) is the primary and most effective treatment for non-metastatic nasopharyngeal carcinoma (NPC), exerting antitumor effects by modulating immune cells. Distinct subpopulations of immune cells exhibit specific sensitivity to CRT. This study aimed to characterize the dynamics of the proportions and absolute counts of peripheral circulating lymphocyte subsets in non-metastatic NPC before and after CRT, and to elucidate their association with clinical responses.

A total of 91 patients with non-metastatic NPC were enrolled. Flow cytometry was employed to detect the expression of CD3, CD4, CD8, CD56, and CD19 on peripheral blood cells. The composition of lymphocyte subsets before treatment, post-completion of CRT, and one month following CRT was retrospectively analyzed. Further, the relationship between the composition of circulating lymphocyte subpopulations and distinguish clinical responses was evaluated.

The proportion of CD3+ T cells showed an initial increase followed by a significant decrease at baseline, post-completion of CRT, and one month following CRT. The proportions of CD3+CD4+ T cells, CD4+/CD8+ ratio, and CD19+ B cells continued to decline at baseline, post-completion of CRT, and one month following CRT, while the proportions of CD3+CD8+ T cells and CD16+CD56+ NK cells progressively increased. The absolute counts of circulating lymphocyte subsets, including CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD45+, CD19+ B cells, and CD16+CD56+ NK cells, demonstrated a trend of initial decrease followed by an increase at baseline, post-completion of CRT, and one month following CRT. Patients with complete response (CR) and partial response (PR) presented similar dynamic trends in the percentages and absolute counts of circulating lymphocyte subpopulations at baseline, post-completion of CRT, and one month following CRT. The proportions and absolute counts of CD3+CD4+ T cells in CR patients were distinctly higher than those in PR patients at the end of CRT, whereas the absolute counts of CD16+CD56+ NK cells were remarkably lower in CR patients compared to PR patients. The baseline proportion and absolute count of CD19+ B cells, as well as the absolute count of CD3+CD4+ T cells, were significantly higher in CR patients compared with PR patients.

CRT induced dynamic alterations in the peripheral lymphocyte profile of non-metastatic NPC patients. Assessing the variations in the distribution of circulating lymphocyte subsets among patients with different clinical treatment responses will be helpful in developing protocols for the concurrent utilization of immunotherapeutic drugs and CRT.

This study investigates the significance of systemic pan-immune inflammation value (PIV) prior to concurrent chemoradiotherapy (CCRT) in predicting the therapeutic efficacy as well as prognosis of patients with locally advanced cervical squamous cell carcinoma.

A retrospective analysis was conducted on the clinical data of 847 patients with locally advanced cervical cancer (LACC) treated at the Second Hospital of Jilin University between 2016 and 2020. All patients underwent radical CCRT, including platinum-based sensitizing chemotherapy. The PIV was measured as given by: (platelet count × neutrophil count × monocyte count)/lymphocyte count. Logistic regression analysis was utilized to study the effect of PIV on therapeutic response in LACC patients and Kaplan-Meier survival together with Cox proportional hazard model to assess its impact on prognosis.

With the therapeutic effect as the endpoint, the optimal cutoff of PIV (356.0099) was signified via the receiver operating characteristics curve, and patients were grouped and compared based on this value. PIV was determined as an independent predictor of the therapeutic effect in CCRT for LACC (hazard ratio (HR) 1.696, 95% confidence interval (CI) 1.111-2.590). PIV was also an independent predictor of overall survival (OS) (HR 0.540, 95% CI 0.409-0.713, p<0.001) as well as disease-free survival (DFS) (HR 0.680, 95% CI 0.528-0.876, p=0.003). Compared to the low-PIV group, it was noted that individuals with a high PIV exhibited a poorer therapeutic effect and shorter OS and DFS.

Patients with LACC and high PIV had poorer therapeutic outcomes and shorter OS and DFS. Our results may provide PIV as a new prognostic biomarker for LACC, if future prospective studies with large patient numbers support our findings.

Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein-Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes.

This multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

OS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility.

Early treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.

A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression. A significant question in the field is how the release and composition of tumor exosomes are regulated. In this perspective article, we explore how physical factors such as geometry and tissue mechanics regulate cell cortical tension to influence exosome production by co-opting the biophysics as well as the signaling dynamics of intracellular trafficking pathways and how these exosomes contribute to the suppression of anti-tumor immunity and promote metastasis. We describe a multiscale modeling approach whose impact goes beyond the fundamental investigation of specific cellular processes toward actual clinical translation. Exosomal mechanisms are critical to developing and approving liquid biopsy technologies, poised to transform future non-invasive, longitudinal profiling of evolving tumors and resistance to cancer therapies to bring us one step closer to the promise of personalized medicine.

Living cells can perform incredible tasks that man-made micro/nano-sized robots have not yet been able to accomplish. One example is that white blood cells can sense and move to the site of pathogen attack within minutes. The robustness and precision of cellular functions have been perfected through billions of years of evolution. In this context, we ask the question whether cells follow a set of physical principles to sense, adapt, and migrate. Microfluidics has emerged as an enabling technology for recreating well-defined cellular environment for cell migration studies, and its ability to follow single cell dynamics allows for the results to be amenable for theoretical modeling. In this review, we focus on the development of microfluidic platforms for recreating cellular biophysical (e.g., mechanical stress) and biochemical (e.g., nutrients and cytokines) environments for cell migration studies in 3D. We summarize the basic principles that cells (including bacteria, algal, and mammalian cells) use to respond to chemical gradients learned from microfluidic systems. We also discuss about novel biological insights gained from studies of cell migration under biophysical cues and the need for further quantitative studies of cell function under well-controlled biophysical environments in the future.

Immune escape is one of the causes of poor prognosis in breast cancer (BC). Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first speed-limiting enzyme of the hexosamine biosynthesis pathway (HBP) and is essential for the progression of BC. Nevertheless, the mechanism of the influence of GFPT1 in BC immune escape is not clear.

First, the level of GFPT1 in BC was analyzed by starbase, and GFPT1 expression in BC tissues was measured by qRT-PCR, western blot and IHC. Then, the O-GlcNAc levels were detected by western blot. Thereafter, Co-IP was applied to examine the relationship between GFPT1 and PD-L1. At last, a mouse model was constructed for validation in vivo.

Firstly, we discovered that GFPT1 was obviously strengthened in BC. Knockdown or introduction of GFPT1 correspondingly degraded and elevated O-GlcNAc levels in cells. Further researches revealed that there was a reciprocal relationship between GFPT1 and PD-L1. Mechanistically, we disclosed that GFPT1 enhanced PD-L1 protein stability through O-glycosylation. More interestingly, GFPT1 accelerated BC cell immune escape via upregulation of O-glycosylation-modified PD-L1. In vivo, silencing of GFPT1 attenuated immune escape of BC cells by reducing PD-L1 levels.

GFPT1 promoted BC progression and immune escape via O-glycosylation-modified PD-L1. GFPT1 may be a potential target for BC therapy.

The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

Cinobufagin (CBG), a key bioactive component in cinobufacini, exhibits antitumor properties. This study explores CBG's impact on triple-negative breast cancer (TNBC) metastasis and elucidates the underpinning mechanism.

Murine xenograft and orthotopic metastatic TNBC models were generated and treated with CBG. The burden of metastatic tumor in the mouse lung, the epithelial to mesenchymal transition (EMT) markers, and macrophage polarization markers within the tumors were examined. The phenotype of tumor-associated macrophages (TAMs) and mobility of TNBCs in vitro in a macrophage-TNBC cell coculture system were analyzed. Physiological targets of CBG were identified by bioinformatics analyses.

CBG treatment significantly alleviated lung tumor burden and EMT activity. It triggered an M2-to-M1 shift in TAMs, resulting in decreased TNBC cell migration, invasion, and EMT in vitro. CBG upregulated membrane metalloendopeptidase (MME) expression, suppressing FAK and STAT3 phosphorylation. Silencing of MME, either in mice or TAMs, counteracted CBG effects, reinstating M2 TAM predominance and enhancing TNBC cell metastasis. Cotreatment with Defactinib, a FAK antagonist, reversed M2 TAM polarization and TNBC cell metastasis. Notably, MME silencing in TNBC cells had no impact on CBG-suppressed malignant properties, indicating MME's indirect involvement in TNBC cell behavior through TAM mediation.

This study unveils CBG's ability to enhance MME expression, deactivate FAK/STAT3 signaling, and inhibit TNBC metastasis by suppressing M2-skewed macrophages.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

In locally advanced rectal cancers (LARC), tumour node metastasis (TNM) staging is far from optimal. The authors aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis.

Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centres. A Cox regression and Kaplan-Meier analysis were performed.

Post-treatment platelet-to-lymphocyte ratio (PLR) predicted pathological complete response. The neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas the platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, the PN index predicted patients with a higher risk of disease-free survival.

Blood parameters might allow the definition of subgroups of risk beyond TNM for the application of different therapeutic strategies.

An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs.

A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery.

Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 μm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups.

Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations. We apply this framework to explore the link between trafficking, signaling in the tumor microenvironment, and cell fate. At each stage, we aim to connect the results of our predictions with cellular experiments.

A new non-invasive biomarker, the Systemic Immune-Inflammation Index (SII), has been proven to have prognostic value in multiple cancers. This systematic review and meta-analysis aimed to investigate the prognostic and clinical pathological significance of SII in urothelial carcinoma.

A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Embase, Cochrane Library, and CNKI. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated to evaluate the prognostic value of SII before treatment on survival outcomes, and odds ratios (OR) with 95%CI were used to assess the correlation between SII before treatment and clinical pathological features.

This meta-analysis included a total of 10 studies (11 datasets) with 6,333 patients. The pooled analysis showed that high SII before surgery was significantly associated with poor survival outcomes in patients with urothelial carcinoma, including overall survival (OS) (HR=1.55, 95%CI 1.24-1.95, p<0.001), cancer-specific survival (CSS) (HR=2.74, 95%CI 1.67-4.49, p<0.001), recurrence-free survival (RFS) (HR=2.74, 95%CI 1.67-4.49, p<0.001), and progression-free survival (PFS) (HR=1.66, 95%CI 1.36-2.02, p<0.001). In addition, patients with elevated preoperative SII values were more likely to have adverse pathological features, including larger tumor size and advanced pathological T stage (p<0.001).

These findings suggest a significant association between high SII levels before treatment and poor survival outcomes, as well as certain clinical pathological features, in patients with urothelial carcinoma.

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to play a diagnostic and predictive role in gestational trophoblastic disease. However, the conclusions are still ambiguous. This meta-analysis aimed to evaluate the combined predictive value of NLR and PLR in the malignant progression of gestational trophoblastic disease. Method: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and China Biomedical Literature Database were searched for the relevant literature published up to 1 October 2022. Study selection and data extraction were performed independently by two reviewers. All analyses were performed using Revman, MetaDisc and STATA software. Results: A total of 858 patients from five studies were included in this meta-analysis. The pooled sensitivity and specificity of NLR were 0.8 (95% CI: 0.71-0.88) and 0.73 (95% CI: 0.69-0.76), respectively, and the area under curve of the summary receiver operating curve was 0.81. The pooled sensitivity and specificity of PLR were 0.87 (95% CI: 0.75-0.95) and 0.49 (95% CI: 0.44-0.54), respectively, and the area under curve of the summary receiver operating curve was 0.88. I2 statistic and Deek's funnel plot showed no heterogeneity and publication bias. Conclusion: NLR can accurately predict the progression from hydatidiform mole to gestational trophoblastic neoplasia and is a promising biomarker in further follow-up.

Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored.

The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens.

Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)).

Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes.

Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t-tests or Mann-Whitney tests. The paired t-test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model.

Compared with the control group, the NPC group showed significant decreases in the proportions of CD3+ cells, CD4+ T cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4+ cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio were markedly decreased (P<0.05), while the proportions of CD8+ T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19+ B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05).

The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19+ B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.

To investigate the impact of preoperative systemic immune inflammatory index (SII) on the clinical prognosis of patients undergoing colorectal cancer (CRC) surgery.

One hundred and sixty CRC patients who underwent surgical treatment in our gastrointestinal surgery department from January 2019 to May 2023 were collected. ROC curves were applied to determine the sensitivity and specificity of SII, determine the optimal cut-off value into low SII and high SII groups, compare the clinicopathological data of SII patients in the two groups, and analyze the postoperative survival of patients in the two groups using Kaplan-Meier and Log-rank methods. Univariate and multifactor COX proportional risk regression models were used to analyze clinical prognostic factors.

The ROC curve showed that the area under the curve of SII for the evaluation of OS in CRC patients was 0.859, and the best cut-off value was 513.53. There was statistical significance (P < 0.05) in terms of tissue grading and diabetes mellitus in both groups. The Kaplan-Meier survival curves showed that the overall survival rates of the SII<513.53 group and the SII≥513.53 group were 50.88% (29/57) and 32.04% (33/103), and the overall survival rate of the SII<513.53 group was significantly higher than that of the SII≥513.53 group, and the difference was statistically significance (χ2 = 8.375, P=0.004). COX proportional risk regression showed that TNM stage, lymph node metastases, anastomotic fistula and SII were independent risk factors affecting postoperative survival in patients with CRC.

Preoperative SII is an independent prognostic factor for CRC, which is simple, convenient, and non-invasive, and can be used to predict the prognosis of CRC patients.

Inflammatory markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) are linked with the pathogenesis of gastric cancer (GC). However, the clinical significance of the combination of these markers is unclear. Hence, this study was carried out to determine the individual and combined diagnostic accuracy of NLR, PLR and MLR among patients with GC.

In this prospective, cross-sectional study, patients were recruited into three groups, GC, precancerous lesions and age and gender-matched controls. The primary outcome was to determine the diagnostic accuracy of inflammatory markers in the diagnosis of GC. The secondary outcome was to determine the correlation of inflammatory markers with the stage of gastric cancer, nodal involvement and metastasis.

A total of 228 patients, 76 in each group, were enrolled. The cut-off value of NLR, PLR and MLR were 2.23, 146.8 and 0.26, respectively, for the diagnosis of GC. The diagnostic abilities of NLR, PLR and MLR were significantly high at 79, 75 and 68.4, respectively, to predict GC compared to precancerous and control groups. All the models of inflammatory markers showed excellent discrimination between GC and the controls with an AUC > 0.7. The models also showed acceptable discrimination between GC and the precancerous lesion group with AUC between 0.65 and 0.70. No significant difference was found in correlating inflammatory markers with clinicopathological features.

The discrimination capacity of the inflammatory markers could be used as screening biomarkers in diagnosing GC, even in its early stages.

Tumour development is greatly influenced by the systemic inflammatory response. Inflammatory factors, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphcyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), mirror the balance between systemic inflammation and anti-tumour response. The current investigation examined the predictive and prognostic value of NLR, PLR, and LMR in advanced gastric cancer (GC) patients.

This study is a retrospective, observational analysis involving 105 GC patients treated with neoadjuvant chemotherapy (NAC). Thestudy population included patients who met the eligibility criteria.The relationship between NLR, PLR, LMR and demographic and clinical variables was assessed using theΧ2test. Survival data were analysed by Kaplan-Meier curves.

High NLR levels were associated with more advanced tumour stage.Higher risk of no tumour regression after NAC was observed if a high pretreatment level of NLR or PLR was found. All patients with an increase in NLR after NAC had a significantly higher risk of no tumor response.In groups high (no change), increase, decrease, and low (no change), NLR and PLR OS medians were: 33, 67, 78, and not reached-NR and 34, 29, 36, and NR, respectively. All patients had a significantly higher risk of death if NLR increased after NAC. An increase in post-NAC PLR level was associated with an increased risk of death only if the PLR baseline value was low.

NLR and PLR are promising predictive and prognostic factors in advanced GC patients treated with NAC.

To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib.

A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR.

Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.

Recently, there has been a growing focus on the prognostic significance of nutrition-related biomarkers. We attempted to explore the association between a novel albumin-related nutrition marker called "lymphocyte × albumin (LA)" and disease-free survival (DFS) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).

In total, 711 non-metastatic breast cancer patients who underwent NAC at two medical centers were retrospectively analyzed. We performed least absolute shrinkage and selection operator (LASSO) Cox regression analysis as well as multivariate Cox regression analyses to identify the variables associated with DFS and to establish a predictive nomogram.

The nomogram incorporated four variables based on the multivariate analysis of DFS in the training cohort: LA, ypN stage, ypT stage, and hormone receptor status. In comparison with the traditional TNM staging system, the nomogram demonstrated superior discrimination, calibration ability, and clinical usefulness in both the training set and internal and external validation sets. Furthermore, patients stratified into different risk groups resulted in significant differences in DFS.

LA is an independent prognostic biomarker, and LA-based prognostic nomogram offers a more precise assessment of DFS for breast cancer patients treated with NAC, potentially serving as a valuable tool for personalized prognostic predictions.

This study aims to investigate the predictive value of the combined index smni(skeletal muscle index (SMI)-prognostic nutrition index(PNI)) for the postoperative survival of patients with advanced gastric cancer(AGC).

650 patients with AGC from two centers (290 cases from the First Affiliated Hospital of Dalian University and 360 points from the Fujian Medical University Union Hospital) were selected as the study subjects based on unified screening criteria. Clinical data, preoperative abdominal CT images, results of hematology-related examinations, tumor-related characteristics, and surgical and follow-up data of the patients were collected and organized. The L3 vertebral level muscle area was measured using computer-assisted measurement techniques, and the skeletal muscle index(SMI) was calculated based on this measurement. The prognostic nutrition index (PNI) was calculated based on serum albumin and lymphocyte count indicators. The Kaplan-Meier survival analysis of data from the First Affiliated Hospital was used to determine that SMI and PNI are significantly correlated with the postoperative survival rate of patients with advanced gastric cancer. Based on this, a novel combined index smni was fitted and stratified for risk. Cox proportional hazards regression analysis was used to determine that the index smni is an independent prognostic risk factor for patients with AGC after surgery. The ROC curve was used to describe the predictive ability of the new combined index and its importance and predictive power in predicting postoperative survival of patients with AGC, which was verified in the data of Fujian Medical University Union Hospital.

The Kaplan-Meier curve analysis of the combined indicator smni Is clearly associated with long-term survival(3-year OS (P < 0.001) and DSS (P < 0.001)), univariate analysis and multivariate analysis showed that smni was an independent prognostic risk factor, The ROC curve for the first center 3-year OS(AUC = 0.678), DSS(AUC = 0.662) show good predictive ability and were validated in the second center.

The combined index smni has a good predictive ability for the postoperative survival rate of patients with AGC and is expected to provide a new reference basis and more accurate and scientific guidance for the postoperative management and treatment of patients with AGC.

To clarify the relationship between preoperative platelet count/(lymphocyte count × prealbumin count) ratio (PLPR) and the prognosis of patients with gastric cancer undergoing a radical operation, combined with Tumor Node Metastasis (TNM) staging, a scoring system was established to guide clinical application.

The clinical data of 238 patients receiving radical operations for gastric cancer were retrospectively analyzed. According to the area under the Receiver operating characteristic curve, the predictive value of the preoperative PLPR for the 5-year overall survival (OS) of gastric cancer was determined, and the best cut-off value of the ratio was corresponding to the maximum value of Yoden index. Chi-squared test was applied to analyze the correlation between the ratio and clinicopathological features. Kaplan-Meier curve was applied to analyze the influence of this ratio on 5-year OS. The Cox regression model was applied to analyze the hazards affecting the long-term survival of patients. The nomogram model was used to predict the long-term survival rate.

The optimal cut-off point of preoperative PLPR ratio was 7.46, and the patients were segmented into two sets: one set of ratio <7.46 and another set of ratio ≥7.46. The ratio was correlated with the size of the tumor, T stage, N stage, total stage, vascular cancer thrombus, and nerve invasion. In stage I-III patients, the prognosis was better in the low-ratio set than in the high-ratio set (P < 0.001), subgroup analysis indicated the prognosis was obviously better in the low-ratio set than in the high-ratio set in stage II and III patients (P < 0.05 and P < 0.001), but there was no difference in stage I patients (P > 0.05). Age, T stage, N stage, total TNM stage, tumor size, vascular tumor thrombus, nerve invasion, preoperative neutrophil count/lymphocyte count (NLR; reference value 3.68), preoperative PLPR (reference value 7.46), preoperative platelet count/lymphocyte count (PLR; reference value 159.56), and preoperative platelet count × NLR (SII; reference value 915.48) were related to patient prognosis (P < 0.05); meanwhile age, total TNM stage, preoperative PLPR (reference value 7.46), preoperative PLR (reference value 159.56), and preoperative SII (reference value 915.48) were independent hazards for prognosis (P < 0.05). Five independent risk factors were analyzed by nomogram model to predict the 5-year OS of patients who underwent a radical operation for carcinoma of the stomach.

Preoperative PLPR ratio (reference value 7.46) is an independent risk factor for long-term prognosis in patients undergoing a radical operation for gastric cancer. The nomogram scoring system established by postoperative TNM staging combined with this ratio and age, PLR, and SII can better forecast the survival of patients who underwent radical operation for carcinoma of the stomach.

The prognosis of patients with advanced cancers of the upper gastrointestinal (UGI) tract is poor. Systemic chemotherapy forms the basis for their treatment, with limited efficacy. Biomarkers have been introduced into clinical practice for cancer management. This study aimed to investigate the predictive and prognostic values of circulating biomarkers in patients with advanced esophageal and gastric cancers receiving chemotherapy.

Overall, 92 patients with advanced esophageal squamous cell carcinoma (ESCC; n = 38) and gastric adenocarcinoma (GAC; n = 54) were enrolled. We analyzed the association of circulating lymphocyte subsets, inflammatory markers, and blood cell counts with treatment efficacy and patient survival.

Significant differences were identified in peripheral blood parameters between the groups with different clinicopathological features. Hemoglobin (Hb, p = 0.014), eosinophil counts (p = 0.028), CD4⁺CD28⁺T/CD4⁺T percentage (p = 0.049), CD8⁺CD38⁺T/CD8⁺T percentage (p = 0.044), memory CD4⁺T (p = 0.007), and CD4⁺CD28⁺T (p = 0.007) were determined as predictors for achieving non-PD (progression disease) in the ESCC cohort. High levels of eosinophils (p = 0.030) and memory CD4⁺T cells (p = 0.026) and high eosinophil-to-lymphocyte ratio (ELR, p = 0.013) were predictors of non-PD in patients with GAC. The combined detection models exhibited good ability to distinguish between partial response (PR)/non-PR and PD/non-PD in patients with ESCC and GAC, respectively. Using the multivariate Cox model, the Eastern Cooperative Oncology Group (ECOG) score status (hazard ratio [HR]: 4.818, 95% confidence intervals [CI]: 2.076-11.184, p < 0.001) and eosinophil count (HR: 0.276, 95% CI: 0.120-0.636, p = 0.003) were independent prognostic factors of progression-free survival (PFS) in patients with ESCC. Metastatic sites (HR: 2.092, 95% CI: 1.307-3.351, p = 0.002) and eosinophil-to-lymphocyte ratio (ELR; HR: 0.379, 95% CI: 0.161-0.893, p = 0.027) were independent prognostic factors for overall survival (OS) in patients with ESCC. Differentiation (HR: 0.041, 95% CI: 0.200-0.803, p = 0.010), memory CD4⁺T (HR: 0.304, 95% CI: 0.137-0.675, p = 0.003), NK cells (HR: 2.302, 95% CI: 1.044-3.953, p = 0.037), and C-reactive protein-to-lymphocyte ratio (CLR; HR: 2.070, 95% CI: 1.024-4.186, p = 0.043) were independent prognostic factors for PFS in patients with GAC. Total lymphocyte counts (HR: 0.260, 95% CI: 0.086-0.783, p = 0.017), CD8⁺T (HR: 0.405, 95% CI: 0.165-0.997, p = 0.049), NK cells (HR: 3.395, 95% CI: 1.592-7.238, p = 0.002), and monocyte-to-lymphocyte ratio (MLR; HR: 3.076, 95% CI: 1.488-6.360, p = 0.002) were identified as independent prognostic factors associated with OS of GAC.

Lymphocyte subsets, blood cell counts, and inflammatory parameters may predict the chemotherapeutic response and prognosis in ESCC and GAC. A combination of these markers can be used to stratify patients into risk groups, which could improve treatment strategies.

Although endoscopic submucosal dissection (ESD) is considered standard treatment for early gastric cancer (EGC), patients with non-curative resection (NCR) of ESD may still require gastrectomy. The systemic immune-inflammation index (SII) showed great potential in predicting the prognosis of gastric cancer patients. This study aims to investigate the predictive validity of SII of NCR in EGC patients.

We reviewed data from EGC patients who underwent ESD in the past. The relationship between SII and clinicopathologic features was investigated. We used Receiver operating characteristic curves to compare the predictive values of NCR between SII and other inflammation indices. Binary logistic analysis was used to identify independent risk factors for NCR. These factors were then used to construct a predictive nomogram.

SII was associated with larger tumor size, male gender, older age, submucosal invasion, and a greater risk of NCR. SII showed better predictivity of NCR than platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). SII [odds ratio (OR) = 1.003, P = 0.001], NLR (OR = 1.520, P = 0.029), PLR (OR = 1.009, P = 0.010), upper stomach tumors (OR = 16.393, P < 0.001), poorly differentiated type (OR = 29.754, P < 0.001), ulceration (OR = 4.814, P = 0.001), and submucosal invasion (OR = 48.91, P < 0.001) were independent risk factors for NCR. The nomogram model based on these factors exhibited superior concordance and accuracy.

SII could be considered a simple and effective predictor of NCR of ESD in EGC patients.

Lung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection.

We retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese People's Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediate/poor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection.

A total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediate/poor was related to worse RFS and OS (p < 0.05). Preoperative LIPI intermediate/poor, vascular invasion and no adjuvant chemotherapy were indicators of poor OS. Patients with LIPI intermediate/poor had worse OS especially among females and those with adjuvant chemotherapy (p < 0.05). Adjuvant chemotherapy related to better RFS and OS in patients with LIPI good (p < 0.05).

Preoperative LIPI intermediate/poor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation.

Immune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy.

The present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed.

A total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions.

Decreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

Many patients have a higher risk of thyroid cancer if they have both papillary thyroid carcinoma (PTC) and Type 2 diabetes mellitus (T2DM). Meanwhile, the primary reason for local PTC recurrence is cervical lymph node metastasis. Therefore, the prognosis of patients affects how cervical lymph nodes are managed during surgery. Due to surgical complications such as laryngeal nerve palsy and hypocalcemia, it is still debatable whether to prevent central lymph node dissection (CLND). Predicting central lymph node metastasis (CLNM) is crucial to direct CLND. It is unclear how important the fibrinogen-to-neutrophil ratio (FNR) is in thyroid cancer, so we looked into how it might help patients with PTC and T2DM predict CLNM.

Wenzhou Medical University's First Affiliated Hospital provided us with 413 patients with PTC and T2DM, randomly divided into a training set (N = 292) and a validation set (N = 121). Univariate and multivariate logistic regression analyses were used to identify independent risk factors. After constructing a nomogram, the validity of the model was evaluated.

The maximum tumor diameter, high-density lipoprotein, thyroxine, triglyceride, lymphocyte, and FNR were all identified as independent risk factors by multivariate logistic regression analysis. The C index of the training set was 0.775, and the validation set was 0.654.

In patients with PTC and T2DM, preoperative FNR was an independent risk factor for CLNM.

Tumor microenvironment (TME) has been shown to be extensively involved in tumor development. However, the dynamic change of TME components and their effects are still unclear. Here, we attempted to identify TME-related genes that could help predict survival and may be potential therapeutic targets.

Data was collected from UCSC Xena and GEO database. ESTIMATE and CIBERSORT algorithms were applied to estimate the components and the proportions of TIICs in TME. We analyzed the gene expression differences of immune components and stromal components, respectively, and finally got the overlapped DEGs. Through protein-protein interaction (PPI) network and univariate Cox regression analysis based on shared DEGs, we screened out and validated the TME-related genes. Focusing on this gene, we analyzed the expression and prognostic value of this gene, and investigated its relationship with immune cells by correlation analysis, single cell analysis, immunohistochemistry and immunofluorescence analysis.

Through a series analysis, we found that the proportion of immune and stromal components was an important prognostic factor, and screened out a key gene, LPAR5, which was highly correlated with prognosis and metastasis. And the expression of LPAR5 was positively correlated with immune cells, especially macrophages, indicating LPAR5⁺ macrophages played an important role in tumor microenvironment of osteosarcoma. Meanwhile, the genes in LPAR5 high expression group were enriched in immune-related activities and pathways, and differentially expressed genes between LPAR5⁺ macrophages and LPAR5^- macrophages were enriched in the biological processes associated with phagocytosis and antigen presentation. What' more, we found that LPAR5 was mainly expressed in TME, and high LPAR5 expression predicting a better prognosis.

We identified a TME-related gene, LPAR5, which is a promising indicator for TME remodeling in osteosarcoma. Particularly, LPAR5⁺ macrophages might have great potential to be a prognostic factor and therapeutic target for osteosarcoma.

Background: The aim of this study was to investigate how the systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), taken individually and combined, are associated with overall survival (OS) in patients surgically treated for malignant salivary gland tumors (MSGTs). Methods: A retrospective analysis of 74 cases following surgery at our department between January 2011 and June 2018 was performed. The Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR. Survival curves of different groups at 1−3−5 years were estimated using the Kaplan−Meier method. Results: The optimal thresholds with the highest sensitivity and specificity were 3.95 for NLR, 187.6 for PLR, 917.585 for SII, and 2.045 for SIRI. The ROC curves revealed that the best combination with AUC = 0.884 was SII + SIRI. The estimated 5-year OS probability in patients with SII+ SIRI scores of 0, 1, and 2 was 96%, 87.5% and 12.5%, respectively (p < 0.001). Conclusion: SII+ SIRI can independently predict the OS of patients after MSGT surgery. The prognostic score system based on SII+ SIRI may be good clinical practice as a reference for clinical decision-making.

Previous investigations suggest that systemic inflammation markers are able to provide prognostic value in several cancers. This study seeks to characterize the ability of pretreatment platelet-to-lymphocyte ratio (PLR) to prognosticate advanced or metastatic gastric cancer patients (AGC or MGC, respectively) receiving immunotherapy.

AGC and MGC patients exposed to PD-1 inhibitors from January 2016-August 2021 in the Chinese PLA General Hospital were recruited. Correlations between PLR and overall survival (OS), progression-free survival (PFS), and immunotherapy-associated tumor response rates were determined.

237 patients were enrolled for this retrospective investigation. The 6 month and 12 month PFS based on the area under the curve value was 0.60 and 0.65 (p < 0.05). based on a calculated PLR cut-off value of 139.41, The PLR < 139.41 group has a longer OS in contrast with the PLR ≥ 139.41 group (13.46 m vs 10.71 m, HR = 0.57, 95% CI 0.42-0.78, p = 0.004). The PLR < 139.41 group had a PFS of 7.93 m in contrast to the 4.75 m seen in those with PLR ≥ 139.41 group (HR = 0.57, 95% CI 0.43-0.76, p = 0.002). The disease control rate (DCR) and objective response rate (ORR) were 86.17% and 30.85%, respectively, in the PLR < 139.41 group, but were 82.52% and 32.17%, respectively in the PLR ≥ 139.41 group. Both groups did not show any marked differences in terms of ORR and DCR (p = 0.887, p = 0.476). PLR is an independent prognostic indicator for OS and PFS upon uni- and multivariate analyses (p < 0.05).

Pre-treatment PLR correlated significantly with PFS and OS in AGC and MGC patients who received immunotherapy. An elevated PLR may provide guidance on subsequent treatment options.