Indicator Of Survival In Patients Research Articles

Tumor-Infiltrating B Cells and Tissue-Resident Memory T Cells as Prognostic Indicators in Brain Metastases Derived from Gastrointestinal Cancers.

Tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) play significant roles in antitumor immunity. However, their prognostic relevance in brain metastases (BMs) derived from gastrointestinal (GI) cancers remains unclear. This study aimed to investigate the prognostic significance of TIBs and TRMs in GI cancer-derived BMs (GIBMs). Retrospective histopathological analyses were performed on surgically resected GIBM tissues from 13 patients. The densities of tumor-infiltrating lymphocytes (TIL) subsets (TIBs, CD4+ T cells, CD8+CD103+ TRMs, and CD8+CD103- non-TRMs) were quantified and correlated with clinical parameters and overall survival (OS) including the Graded Prognostic Assessment (GPA). TIBs and CD4+ T cells were predominantly accumulated in the tumor stroma, particularly around blood vessels, where they formed lymphocyte clusters without characteristics of tertiary lymphoid structures (TLSs). In contrast, TRMs more deeply infiltrated into the tumor epithelium than their counterpart non-TRMs. Positive correlations were found between TIB density and both the prognostic prediction of GPA and overall survival (OS) after BM diagnosis or surgery. Furthermore, increased densities of TIBs and TRMs were associated with enhanced survival after BM diagnosis. TIB and TRM densities in BM tissues could serve as reliable prognostic indicators for survival in patients with GIBMs. This study provides crucial insights for the development of novel immunotherapeutic strategies against this lethal disease.

WHO BREF Quality of Life Score as a Prognostic Indicator of Survival in Patients recovered from COVID-19 Associated Rhino-Orbito-Cerebral Mucormycosis.

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) has emerged as a formidable infection in patients with COVID-19, this study was designed to assess the QOL in patients with and its predictability for survival in CAM victims. This long term prospective observational study of 290 patients with CAM was conducted over 2years using a standard questionnaire (the abbreviated World Health Organization Quality of Life questionnaire [WHO-BREF]), Karnofsky performance scale (KPS), palliative performance scale (PPS) and patient rated improvement (PRI) ranging from 0 to 9. Cut-off values of ≤ median score was considered to indicate poor QOL or poor improvement. The overall 2year survival rate was 78.27% with mean survival time of 763.2 ± 1.2days (Mean ± S.E) (95% CI: 760.76-765.6). The disease specific mortality was 22.1%. The overall mean QOL was 53.5(10.2) with 51% of population exhibiting poor QOL. Spearman rho correlation showed strong positive correlation between the three QOL scales and PRI (ρ-0.72, p < 0.001). On Cox regression analysis the stage, all four domains of WHO BREF, KPS, and PPS were independent predictors of long term survival in CAM patients. Approximately half of the patients with CAM had poor QOL and poor improvement. All 4 domains of WHO BREF score can be used as a predictor of long term survival in CAM patients. Early recognition is the key to optimal treatment, improved outcomes, and improved QOL in patients with CAM.

Identification of Plasma Lipid Alterations Associated with Melanoma Metastasis.

The aim of this study was to apply a state-of-the-art quantitative lipidomic profiling platform to uncover lipid alterations predictive of melanoma progression. Our study included 151 melanoma patients; of these, 83 were without metastasis and 68 with metastases. Plasma samples were analyzed using a targeted Lipidyzer™ platform, covering 13 lipid classes and over 1100 lipid species. Following quality control filters, 802 lipid species were included in the subsequent analyses. Total plasma lipid contents were significantly reduced in patients with metastasis. Specifically, levels of two out of the thirteen lipid classes (free fatty acids (FFAs) and lactosylceramides (LCERs)) were significantly decreased in patients with metastasis. Three lipids (CE(12:0), FFA(24:1), and TAG47:2-FA16:1) were identified as more effective predictors of melanoma metastasis than the well-known markers LDH and S100B. Furthermore, the predictive value substantially improved upon combining the lipid markers. We observed an increase in the cumulative levels of five lysophosphatidylcholines (LPC(16:0); LPC(18:0); LPC(18:1); LPC(18:2); LPC(20:4)), each individually associated with an elevated risk of lymph node metastasis but not cutaneous or distant metastasis. Additionally, seventeen lipid molecules were linked to patient survival, four of which (CE(12:0), CE(14:0), CE(15:0), SM(14:0)) overlapped with the lipid panel predicting metastasis. This study represents the first comprehensive investigation of the plasma lipidome of melanoma patients to date. Our findings suggest that plasma lipid profiles may serve as important biomarkers for predicting clinical outcomes of melanoma patients, including the presence of metastasis, and may also serve as indicators of patient survival.

Abstract 5210: The Prognostic value of serum TK1 protein determinations using AroCell TK210 ELISA in DLBCL patients treated with R CHOP

Abstract Background: Diffuse large-cell B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphomas (NHL) that accounts for approximately 25% of the patients. Earlier studies demonstrated the prognostic value of serum thymidine kinase 1 (STK1) activity determinations in different hematological malignancies. To date, the prognostic value of STK1 protein concentration in patients with DLBCL treated with R-CHOP has not been investigated. The purpose of this retrospective study was to determine the value of high TK levels on Overall survival among DLBCL patients treated with R-CHOP as first-line treatment. Materials and Methods: The study included 146 patients diagnosed with DLBCL between 2010 and 2016 from the Uppsala-Umeå Comprehensive Cancer Consortium (U-CAN). All patients included were treated using the standard chemotherapy regimen R-CHOP. Serum samples were collected at the time of diagnosis, during the treatment, 1 year after treatment, and after relapse. Non-infected and apparently healthy persons, matched to the DLBCL patients (57 males and 88 females), served as controls. The TK1 protein levels in all serum samples were determined by using AroCell TK 210 ELISA (AroCell AB, Sweden). The TK1 protein concentration was expressed as μg/L. Results: The TK1 concentrations in sera from DLBCL patients before treatment were significantly higher compared to the concentrations in healthy individuals, median 0.44 μg/L (IQ range 0.22 to 1.06 μg/L) vs. median 0.22 μg/L (IQ range 0.18 to 0.29 μg/L, P&amp;lt;0.00001). Serum TK1 was also significantly higher in patients with more advanced stages (P&amp;lt;0.00001), higher IPI (P&amp;lt;0.00001), and in patients with B-symptoms (P&amp;lt;0.0001). Patients with STK1 protein levels below the cut-off value (0.45 μg/L) had significantly better OS and DFS (P=0.04 and P=0.0006, respectively) compared to patients with STK1 concentration above the cut-off. In multivariate analyses, dichotomized S-TK1 measurements before treatment were found to be significant for the risk of relapse in combination with either aaIPI or IPI (p&amp;lt;0.01). Conclusions: These results confirmed that STK1 concentration correlates with risk factors such as tumor burden, Ann Arbor stage, and IPI. In conclusion, patients with high TK1 concentrations at the time of diagnosis have short overall survival and STK1 concentrations are apparently a prognostic indicator for survival in patients treated with modern chemo-immunotherapy. Citation Format: Kiran Jagarlamudi, Gustaf Hedström, Per Venge, Staffan Eriksson, Daniel Molin, Gunilla Enblad. The Prognostic value of serum TK1 protein determinations using AroCell TK210 ELISA in DLBCL patients treated with R CHOP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5210.

Integrating single-cell and bulk sequencing data to identify glycosylation-based genes in non-alcoholic fatty liver disease-associated hepatocellular carcinoma.

The incidence of non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) has been increasing. However, the role of glycosylation, an important modification that alters cellular differentiation and immune regulation, in the progression of NAFLD to HCC is rare. We used the NAFLD-HCC single-cell dataset to identify variation in the expression of glycosylation patterns between different cells and used the HCC bulk dataset to establish a link between these variations and the prognosis of HCC patients. Then, machine learning algorithms were used to identify those glycosylation-related signatures with prognostic significance and to construct a model for predicting the prognosis of HCC patients. Moreover, it was validated in high-fat diet-induced mice and clinical cohorts. The NAFLD-HCC Glycogene Risk Model (NHGRM) signature included the following genes: SPP1, SOCS2, SAPCD2, S100A9, RAMP3, and CSAD. The higher NHGRM scores were associated with a poorer prognosis, stronger immune-related features, immune cell infiltration and immunity scores. Animal experiments, external and clinical cohorts confirmed the expression of these genes. The genetic signature we identified may serve as a potential indicator of survival in patients with NAFLD-HCC and provide new perspectives for elucidating the role of glycosylation-related signatures in this pathologic process.

Quantitative peritumoral magnetic resonance imaging fingerprinting improves machine learning-based prediction of overall survival in colorectal cancer.

To investigate magnetic resonance imaging (MRI)-based peritumoral texture features as prognostic indicators of survival in patients with colorectal liver metastasis (CRLM). From 2007-2015, forty-eight patients who underwent MRI within 3 months prior to initiating treatment for CRLM were identified. Clinicobiological prognostic variables were obtained from electronic medical records. Ninety-four metastatic hepatic lesions were identified on T1-weighted post-contrast images and volumetrically segmented. A total of 112 radiomic features (shape, first-order, texture) were derived from a 10 mm region surrounding each segmented tumor. A random forest model was applied, and performance was tested by receiver operating characteristic (ROC). Kaplan-Meier analysis was utilized to generate the survival curves. Forty-eight patients (male:female = 23:25, age 55.3 years ± 18 years) were included in the study. The median lesion size was 25.73 mm (range 8.5-103.8 mm). Microsatellite instability was low in 40.4% (38/94) of tumors, with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation detected in 68 out of 94 (72%) tumors. The mean survival was 35 months ± 21 months, and local disease progression was observed in 35.5% of patients. Univariate regression analysis identified 42 texture features [8 first order, 5 gray level dependence matrix (GLDM), 5 gray level run time length matrix (GLRLM), 5 gray level size zone matrix (GLSZM), 2 neighboring gray tone difference matrix (NGTDM), and 17 gray level co-occurrence matrix (GLCM)] independently associated with metastatic disease progression (P < 0.03). The random forest model achieved an area under the curve (AUC) of 0.88. MRI-based peritumoral heterogeneity features may serve as predictive biomarkers for metastatic disease progression and patient survival in CRLM.

Prognostic value of 18F-FDG PET/CT tumor metabolic parameters and Ki-67 in pre-treatment diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive lymphoma. Rituximab-based conventional chemotherapy still leads to drug resistance or relapse in 30-40% of patients. Therefore, early identification of high-risk patients and accurate assessment of prognosis are very important for clinical decision-making. The aim of this study is to investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of tumor metabolic, clinical and biological parameters in the prognostic risk stratification of DLBCL before treatment. We retrospectively collected clinical data on 63 patients with newly diagnosed DLBCL admitted to Shanxi Bethune Hospital during the period from November 2016 to April 2020 who underwent 18F-FDG PET/CT prior to treatment in a cohort study. Metabolic, clinical, and biological parameters were analyzed by Cox regression. Kaplan-Meier curves of patient survival were compared by the log-rank test. The median follow-up was 21 months. The 2-year progression-free survival (PFS) was 47.62%, and the overall survival (OS) was 53.97%. The subtype, double expression, Ann Abor stage, NCCN-IPI score, Ki-67, maximum standardized uptake value (SUVmax), bulk volume glycolysis (BVG), total lesion glycolysis (TLG), total metabolic tumor volume (TMTV) were the influencing factors for PFS and OS (P<0.050) in univariate analysis. BVG (PFS: HR =6.62, P<0.001; OS: HR =3.53, P=0.029), TLG (PFS: HR =8.56, P<0.001; OS: HR =5.20, P=0.004), TMTV (PFS: HR =12.02, P=0.001; OS: HR =5.05, P=0.033) and Ki-67 were found to be independent prognostic risk stratification parameters affecting PFS and OS by multivariate regression analysis. The 2-year PFS and OS rates for patients with high BVG (≥288.00 cm3), TLG (≥1,854.00 cm3), TMTV (≥103.00 cm3), and Ki-67 (≥85%) were 20% and 28.57%, 9.68% and 22.58%, 20.51%, and 30.77%, and 25% and 33.33%, respectively; and the 2-year PFS and OS rates for patients with low BVG (<288.00 cm3), TLG (<1,854.00 cm3), TMTV (<103.00 cm3), and Ki-67 (<85%) patients were 82.14% and 85.71%, 84.37% and 84.37%, 91.67% and 91.67%, and 61.54% and 66.67%, respectively. Patients with high BVG, TLG, TMTV, and Ki-67 had a worse 2-year PFS as well as OS rate (Ki-67: P=0.0018/P=0.0025; P<0.0001 for the rest of the groups). Our findings suggest that BVG, TLG, TMTV, and Ki-67 are independent prognostic indicators for survival in patients with pre-treatment DLBCL, especially BVG, which is a novel prognostic indicator that has to be validated in future research.

Analysis of Expression of Programmed Cell Death Ligand 1 (PD-L1) and BRAFV600E Mutation in Thyroid Cancer.

In thyroid cancer, it has been suggested that PD-L1 overexpression is associated with some clinicopathological factors and prognosis. The aim of this study is to characterize the expression of PD-L1, the presence of the BRAFV600E mutation, as well as cellular and humoral immunity in thyroid cancer, and to investigate the factors that predict the effectiveness of anti-PD-L1 antibody therapy. Blood samples were collected from 33 patients who were newly diagnosed with thyroid cancer after surgery or biopsy. PD-L1 expression, BRAFV600E mutation, and CD8+ expression were examined by immunohistological staining using clinical thyroid cancer specimens. With a PD-L1 staining cut-off value of 1%, 13 (39.4%) patients were classified as PD-L1 positive. Stimulation Index (SI) is an indicator of T cell activation. PD-L1 expression was significantly correlated with low SI level (p = 0.046). Moreover, BRAFV600E mutation was detected in 24 of the 33 (72.7%) patients, and was significantly associated with PD-L1 expression (p = 0.047). In addition, enhanced CD8+ expression was significantly associated with PD-L1 expression (p = 0.003). Multivariate analyses confirmed that high CRP levels (p = 0.039) were independently and significantly associated with poor progression-free survival. These findings suggest that elevated PD-L1 status can be a prognostic indicator for survival in patients with thyroid cancer when comprehensively assessed using the expression of CD8+, the presence of BRAFV600E mutation and the patient's immune status.

Association between marital status and all-cause mortality of patients with metastatic breast cancer: a population-based study

This study aimed to investigate the association between marital status and the prognosis of patients with metastatic breast cancer (MBC). Data of patients with MBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into married and unmarried groups. Kaplan–Meier analysis with the log-rank test was conducted to compare breast cancer-specific survival (BCSS) and overall survival (OS) between the groups. Univariable and multivariable Cox proportional models were used to determine whether marital status was independently associated with OS, and the Fine–Gray subdistribution hazard method was performed to determine whether marital status was independently associated with BCSS. In total, 16,513 patients with MBC were identified, including 8949 married (54.19%) and 7564 unmarried (45.81%) patients. The married patients were significantly younger [median age (interquartile range), 59.0 (50.0–68.0) vs. 63.0 (53.0–75.0); p < 0.001] and received more aggressive treatments, such as chemotherapy (p < 0.001) and surgery (p < 0.001), than the unmarried patients. Moreover, married patients had higher 5-year BCSS (42.64% vs. 33.17%, p < 0.0001) and OS (32.22% vs. 21.44%, p < 0.0001) rates. Multivariable analysis revealed that marital status was an independent prognostic factor, and married status was associated with a significant reduction in the risk of breast cancer-specific (sub-hazard ratio, 0.845; 95% confidence interval, 0.804–0.888; p < 0.001) and all-cause (hazard ratio, 0.810; 95% confidence interval, 0.777–0.844; p < 0.001) mortality. Unmarried patients had a 15.5% increased risk of breast cancer-specific mortality and a 19.0% increased risk of overall mortality compared with married patients with MBC. BCSS and OS were superior in married populations compared with unmarried populations in most subgroups. Marital status was an independent prognostic indicator for survival in patients with MBC and was associated with significant survival benefits.

Total T Cell Density and Expression of T Memory Stem Cell Markers are Associated with Better Prognosis in Colon Cancer.

Immune checkpoint inhibitors have achieved limited clinical effectiveness in colon cancer. Stem memory T cells (TSCMs) and in-situ cytotoxic T cells are dominant contributors to host immunity. Currently, data on the correlation between TSCM and T cell abundance and clinicopathological characteristics in colon cancer are largely unavailable. In-situ cytotoxic T cells are identified based on the quantification of CD3+ and CD8+ markers using immunohistochemistry (IHC) in the core of the tumor and the invasive margin of the tumor. The expression of representative markers of TSCMs, CD27 and CD95, was assayed using IHC in colon cancer tissues. Correlations between the levels of each marker and the clinicopathological characteristics as well as prognosis were evaluated. High densities of CD3+ and CD8+ T cells correlated with stage I-II tumors, whereas a lower infiltration of cytotoxic T cells correlated with advanced-stage tumors. CD27 and CD95 were both expressed in the membrane of T cells present in the tumor stroma and their levels showed a negative correlation with the TNM stage. CD3, CD8, and CD27 were expressed at the same locations simultaneously, indicating their coordinated action against cancer. In addition, cytotoxic T cell densities and CD27 and CD95 expression remained independent prognostic factors for overall survival. In-situ cytotoxic T cells and TSCMs play important roles in colon cancer development. TSCMs marker CD27 and CD95 were both indicators of survival in patients with colon cancer. Thus, it is believed that TSCMs represent a desirable population for future use in combination immunotherapy.

Identification of Potential Indicators for Survival in Patients with Thyroid Cancer Based on Expression of FAM3 Members.

Thyroid cancer (THCA) is a common head and neck malignancy. The family with sequence similarity 3 (FAM3) is a cytokine-like gene family with four members, which is presumed to participate in the development of many cancer types. However, the expression patterns of FAM3s in THCA and their prognostic values, have not yet been established. We investigated differential expressions of FAM3 mRNA and protein in THCA, then validated the findings for FAM3B by immunohistochemistry. We also investigated survival data with respect to FAM3 expression patterns in patients with THCA. FAM3s information regarding their relationships with clinical pathological parameters were obtained and FAM3 mutations were assessed. KEGG and GO pathway regarding FAM3C were obtained using online databases. To investigate potential correlations between FAM3s and immune cell infiltration, we investigated the roles of FAM3s in immune cells of patients with THCA. The mRNA expression of FAM3C were significantly elevated in THCA tissues; high expression levels of FAM3C protein were also observed in THCA tissues. A significant association between the pathological stage and the expression of FAM3C was found in patients with THCA. Patients with THCA who had high mRNA expression levels of FAM3C exhibited significantly more favorable prognosis, compared with patients who had low mRNA expression levels of FAM3C. Overall, FAM3C may play vital roles in the pathogenesis and development of THCA, and these findings constitute novel insights for biomarkers of immunotherapeutic targeted agents and may aid in the identification of prognostic biomarkers for THCA.

Association of sarcopenia and its components with clinical outcomes in patients undergoing peritoneal dialysis.

Further studies are needed to identify whether muscle mass, muscle strength, or sarcopenia is the best indicator of survival in patients undergoing peritoneal dialysis (PD). We aimed to compare the association of sarcopenia and its components with survival in patients undergoing PD. We identified all patients with PD (n = 199). We routinely recommended handgrip strength (HGS) and lean mass measurements using dual energy X-ray absorptiometry in all patients with PD. Sarcopenia was defined using cutoff values from the Asian Working Group for Sarcopenia. We evaluated the patient and technique survival rates. The number of patients with low HGS was 95 (47.7%). The median follow-up interval was 17 months (interquartile range, 13-21 months). Kaplan-Meier curve analysis showed that patients with low HGS or sarcopenia had poorer patient and technique survival compared with patients with normal HGS or without sarcopenia. Cox regression analysis showed that patients with low HGS had greater hazard ratios for patient death and technique failure compared with those with normal HGS. However, patients with low muscle mass were not significantly higher hazard ratios for patient death or technique failure compared with those with normal muscle mass. Patients with sarcopenia had significantly greater hazard ratios for patient death or technique failure than those without sarcopenia only in univariate analysis. The present study demonstrated that HGS may be superior to muscle mass or sarcopenia for predicting patient or technique survival in patients undergoing PD.

Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease requiring active management. Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is considered the standard treatment paradigm for MIBC patients, which could result in significant perioperative mortality and morbidity, as well as the significant alteration of the quality of life (QOL). Notably, multimodal bladder-preserving treatment strategies have been recommended for highly selected patients. Pathologic complete response (pCR) after NAC is a powerful prognostic indicator of survival for patients with MIBC. Clinical complete response (cCR) is then introduced as a complementary endpoint for pCR to assess disease status preoperatively. Bladder preservation strategy for patients who achieve cCR following NAC is emerging as a new treatment concept. However, the efficiency of the conservative strategy remains controversial. In this state-of-the-art review, we discuss the advantages and limitations of cCR and the feasibility and safety of bladder preservation strategy in highly selected MIBC patients who achieve cCR following NAC. We conclude that a conservative strategy can be considered a reasonable alternative to RC in carefully selected cCR MIBC patients, leading to acceptable oncological outcomes.

Significance of dysplasia in bile duct resection margin in patients with extrahepatic cholangiocarcinoma: A retrospective analysis.

BACKGROUNDRadical resection is the only indicator associated with survival in extrahepatic cholangiocarcinoma (EHCC). However, limited data are available regarding the implications of dysplasia at the resection margin following surgery. AIMTo evaluate the prognostic significance of dysplasia-positive margins in patients diagnosed with EHCC.METHODSWe reviewed the records of patients who had undergone surgery for EHCC with curative intent between January 2013 and July 2017. We retrospectively analyzed the clinicopathological data of 116 patients followed for longer than 3 years. The status of resection margin was used to classify patients into negative low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/carcinoma in situ (CIS) categories.RESULTSBased on postoperative status, 72 patients underwent resection with negative margins, 19 had LGD-positive margins, and 25 showed HGD/CIS-positive margins. The mean survival rates of the patients with negative margins, LGD margins, and HGD/CIS margins were 49.1 ± 4.5, 47.3 ± 6.0, and 20.8 ± 4.4 mo, respectively (P < 0.001). No difference in survival was found between groups with LGD margins and negative margins (P = 0.56). In the multivariate analysis, age > 70 years and HGD/CIS-positive margins were significant independent factors for survival (hazard ratio = 1.90 and 2.47, respectively). CONCLUSIONHGD/CIS margin in resected EHCC is associated with a poor survival. However, the LGD-positive resection margin is not a significant indicator of survival in patients with EHCC.

DOK2 Has Prognostic and Immunologic Significance in Adults With Acute Myeloid Leukemia: A Novel Immune-Related Therapeutic Target.

BackgroundThe role of downstream tyrosine kinase 2 (DOK2), a major member of the DOK family, remains poorly defined in acute myeloid leukemia (AML). Herein, we investigated the expression levels, clinical outcomes, and biological functions of DOK2 in patients with AML.MethodsDatasets were obtained from the Cancer Genome Atlas (TCGA) database for transcriptomic and clinical information. Nomogram construction and assessment were conducted using Cox regression analysis, receiver operating characteristic (ROC) curves, and calibration plots. Public databases, including the Gene Expression Omnibus, Cancer Cell Line Encyclopedia, LinkedOmics, GeneMANIA, TISIDB, and Gene Set Cancer Analysis, were employed for relevant bioinformatic studies. Moreover, we utilized the CIBERSORT algorithm to evaluate the level of infiltration of immune cells into the bone marrow microenvironment.ResultsWe observed that DOK2 transcription levels were markedly upregulated in AML samples (P < 0.001), and its high expression was associated with inferior overall survival (OS) (HR = 2.17, P < 0.001) and disease-free survival (DFS) (HR = 2.50, P < 0.001). ROC curve analysis also showed the reliable diagnostic efficiency of DOK2 in AML. For treatment regimens, patients with high DOK2 expression could significantly prolong OS by receiving hematopoietic stem cell transplantation (HSCT) (P < 0.001), whereas those with low DOK2 expression were more likely to improve DFS by chemotherapy alone rather than HSCT. Nomograms constructed for predicting OS and DFS exhibited satisfactory discrimination and accuracy. Functional enrichment analysis identified that DOK2 was involved in important pathways associated with immune-related activities. Furthermore, CIBERSORT scores reflected negative correlations of DOK2 with activated mast cells and resting CD4+ memory T cells, which indicated its adverse immunomodulatory potential.ConclusionWe suggest that elevated DOK2 expression could be an unfavorable prognostic indicator of survival in patients with AML. Our findings provide new insights into the role of DOK2 in AML, with promising clinical implications.

Myeloid-derived suppressor-like cells - a potential biomarker for prognosis of colorectal cancer?

Background/Aim. Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of immature cells of myeloid origin, which have the ability to inhibit both the innate and adaptive immune response. Due to its immunosuppressive effect, MDSC can promote the growth and progression of cancer. Colorectal cancer (CRC) is one of the most common cancers in the general population for whose advanced stages of the disease there is still no good therapy. In addition to contributing to the development and spread of CRC, MDSC could potentially be markers of its prognosis. The aim of the study was to examine the potential prognostic role of peripheral blood MDSC counts in CRC patients. Methods. In a prospective study we analyzed the possibility of using CD16low granulocytes and mononuclear (M-MDSC) like cells as well as neutrophyl to lymphocyte ratio (NLR), lymphocite to monocyte ratio (LMR), CD16hi/CD16low granulocytes ratio and M/MMDSC like cells ratios before starting of the treatment as a biomarker for overall survival (OS) in patients with CRC. Hazards ratios (HRs) with the corresponding 95% confidence intervals (95%CIs) were calculated to evaluate the prognostic role of MDSCs in cancer. Results. The analysis was performed in 47 patients in stage III and IV CRC according to the TNM/AJCC disease classification. Dependable data were obtained in 32 patients. Patients blood samples are taken before the possible start of treatment (surgery, chemotherapy). Increased percentage and absolute values of CD16low granulocytes as well as absolute values of M-MDSC-like cells have been shown to be associated with shorter overall survival (OS) (p &lt; 0.0066, p &lt; 0.0013 and p &lt; 0.0119, respectively). The relationship of CD16hi/CD16low granulocytes ratio and M/M-MDSC like cells ratio with OS indicated the existence of positive correlations between these parameters, which higher value of this relationship indicated longer survival of patients (p &lt; 0.0054 and p &lt; 0.0426, respectively). Relationship between OS and NLR indicators found statistically significant inverse correlation with NLR (p = 0.0349). No statistical significance was found in the relationship between OS and LMR. Conclusion. This study shows that percent and absolute numbers of CD16low granulocytes, as well as absolute number of M-MDSC like cells, CD16hi/CD16low granulocytes ratio, M/M-MDSC like cells and NLR ratio ratio may be reliable indicators of survival in patients with CRC.

Analysis of relapse-free and overall survival in oncoplastic and organ-preserving surgeries in patients with breast cancer

Purpose of the study. To study the results of relapse-free and overall survival during organ- preserving and oncoplastic surgeries in patients with breast cancer.Materials and methods. A prospective clinical study of 84 patients was carried out in the mammology department on the basis of GBUZ NSO "GKB № 1". The first group of patients (40 patients) underwent OPR with ALAE - oncoplastic resection of the mammary gland with axillary lymphadenectomy. The second group (44 patients) WSR with ALAE - wide sector resection of the mammary gland with axillary lymphadenectomy.During the study, the patients were comparable in age, stage (TNM), histological type, and morphogenetic data. The survival rate was studied by the number of local relapses and distant metastases, using laboratory and instrumental studies. The quality of life was assessed on the basis of anamnestic data (Karnofsky index, ECOG scale).Results. In the first group of patients, disease-free and overall survival rate was 97.5 %. At the same time, a local recurrence was found in a patient with a triple negative tumor type, distant metastases to the lungs in a patient with a HER2/neu-positive type. In the second group, relapse-free survival was 95.4 %, overall - 97.7 %. Relapses in two patients with HER2/neu-positive type, metastases to the lungs in a patient with triple negative type.Conclusion. Relapse-free survival rates are 2.1 % higher in group I patients who underwent oncoplastic resection with axillary lymphadenectomy. And the indicators of overall survival in patients of both groups do not differ relatively.

Predictive Indicators of Brain Metastasis-Free Survival in Patients With Lung Cancer at a Chinese Cancer Center.

IntroductionMetastasis tumors of the brain derive mostly from lung cancer, breast cancer, melanoma, and more commonly among lung cancer patients. Once brain metastasis is diagnosed, the prognosis of untreated patients is shown to be very poor. In this study, we describe the clinical and pathological features of patients with lung cancer at our institution from 2009 to 2021. We also examined factors like gender, type, size, and location of the primary tumor and leukoaraiosis level at the first visit are associated with patients’ brain metastasis-free survival (the time free of brain metastases since the first diagnosis of lung cancer).Materials and methodsWe retrospectively reviewed patients with a final histologic diagnosis of lung cancer from September 2009 to January 2015. The evaluation included history, physical examination, and contrast-enhanced computerized tomography of the chest. Contrast-enhanced magnetic resonance imaging of the head was performed at the first visit and following treatment. The patients’ age, gender, tumor size, histology type, location of the lung tumor, and leukoaraiosis level at the first visit were recorded and correlated to the patients’ brain-metastasis-free survival time.ResultsThe study included 68 patients - 39 males and 29 females -with a mean age of 55.15 years (range 35-69 years). Adenocarcinoma was diagnosed in 47 patients (22 males and 25 females), Squamous carcinoma was diagnosed in 12 patients (9 males and 3 females), non-small cell lung carcinoma was diagnosed in 3 patients (2 males and one female), one male patient had the diagnosis of adenosquamous tumor and 1 male patient had the diagnosis of neuroendocrine tumor. Tumor size was <3 cm in 19 patients, 3-5 cm in 29 patients, 5-10 cm in 17 patients, and three other patients’ size was hard to measure. Of the 68 patients, 10 patients were detected as brain metastasis by magnetic resonance imaging at first diagnosis, 22 patients were diagnosed as brain metastasis during the follow-up visits, 36 patients were not found as brain metastasis until the last visit. According to the Cox regression univariate analysis, two factors were correlated to shorter brain metastasis-free survival: Not-squamous lung carcinoma (SCC) and higher location of the tumor. The multivariate statistical analysis correlated two factors to shorter brain metastasis-free survival: non-SCC histology type and age≥62.ConclusionsIn conclusion, we found that SCC had a lower incidence of brain metastasis in patients than other lung cancer types. According to the Cox regression multivariate analysis, age <62 and SCC were two protective factors of brain metastasis. According to the Cox regression univariate and analysis. The lower location of the tumor was the protective factor of brain metastasis. According to the Cox regression univariate analysis, other parameters, such as gender or tumor size, did not have a role in brain metastasis-free survival in these patients.

Circulating p16-Positive and p16-Negative Tumor Cells Serve as Independent Prognostic Indicators of Survival in Patients with Head and Neck Squamous Cell Carcinomas.

Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.

Role of Cytokines Released During Pyroptosis in Non-Small Cell Lung Cancer.

PurposePyroptosis is a recently discovered highly inflammatory form of programmed cell death, during which the N-terminus of the cleaved Gasdermin protein family forms pores in the cell membrane, leading to cell disintegration and the release of certain intracellular factors, including caspase3, gasdermin E (GSDME), and high mobility group proteins (HMGB1), which trigger a series of secondary inflammatory reactions. Specifically, caspase3 can lyse GSDME and induce pyrolysis, while HMGB1 is released passively after cell membrane destruction. In this study, the roles of these proteins in lung cancer tissues as well as their clinical significance were investigated.Patients and MethodsThe expression levels of GSDME, caspase3, and HMGB1 proteins in lung cancer and paracancerous tissues were determined via immunohistochemical staining, and their relationship with the clinical stage, pathological grade, and survival prognosis of the patients was analyzed. Further, CD8+ T cell accumulation in the above-mentioned tissues was also determined, and differences between them with respect to CD8+T cell distribution were also investigated. Furthermore, the relationships between CD8+ T cell abundance and the expression levels of the above-mentioned proteins were determined via statistical analyses.ResultsLung cancer and paracancerous tissues showed significantly different GSDME, caspase3, and HMGB1 protein expression levels. GSDME expression level and the presence or absence of lymph node invasion were identified as prognostic indicators of survival in patients with lung cancer. Surprisingly, however, HMGB1, which showed a certain level of correlation with the presence or absence of lymph node metastasis, could not be used as a prognostic indicator of survival.ConclusionGSDME may be an important prognostic indicator of survival in patients with lung cancer. However, the effects of HMGB1 expression level and CD8+ T cell abundance on the prognosis of patients with lung cancer still need further investigation.