Overall Survival Rate Of Patients Research Articles

HIPEC for metastatic gastric cancer: Moving the needle towards 3-year survival

IntroductionPrior work has established hyperthermic intraperitoneal chemotherapy (HIPEC) administration as a safe treatment option for select patients with gastric adenocarcinoma and carcinomatosis. However, identifying patients who will maximally benefit from HIPEC remains unclear. This study assessed a single-institution experience with HIPEC for metastatic gastric cancer to identify variables associated with improved survival. MethodsA database of patients treated for metastatic gastric adenocarcinoma at MD Anderson Cancer Center from 2013 to 2022 was queried for patients undergoing HIPEC as part of their treatment regimen. Patients were stratified by overall survival (OS)≥36 months or <36 months and assessed along demographic and clinicopathologic variables to identify factors associated with OS ≥ 36 months. ResultsAmong 104 patients, 1,2, and 3-year OS from diagnosis was 89 %,44 %, and 18 %. Patients with OS ≥ 36 months were more likely to have moderately differentiated tumors, positive cytology only (i.e. no visible carcinomatosis), and lower peritoneal cancer index (PCI) than those with OS < 36 months (p = 0.002, p = 0.01, p = 0.001,respectively). Groups did not otherwise differ with respect to demographic parameters or treatment or pathologic details. Among patients who underwent gastrectomy, those with OS < 36 months had higher pathologic T and N category (p = 0.003 and p = 0.02, respectively). Postoperative mortality was zero in both groups among patients undergoing gastrectomy. ConclusionsHIPEC may provide more durable survival benefit among patients with metastatic gastric cancer with moderately differentiated disease, low PCI, and positive cytology alone. Additionally, among patients who undergo gastrectomy, higher final pathologic T and N category are associated with worse survival. Trials are needed to compare 3-year OS rates in patients treated with HIPEC versus systemic therapy alone.

Cancer-associated Fibroblasts (CAFs) Regulate Lung Cancer Malignant Progression by Transferring SERPINE2 (PN1) Via Exosomes.

Cancer-associated fibroblasts (CAFs), one of the most abundant stromal cell types in tumor microenvironment (TME), have been a potential target for cancer treatment such as lung cancer. However, the underlying mechanism by which CAFs promote lung cancer progression remains elusive. We obtained primary CAFs, normal fibroblasts (NFs) and their exosomes, constructed protease nexin-1 (PN1) stably silenced or over-expressed CAFs cells using lentivirus. Bioinformatics was used to obtain the expression of PN1 in lung cancer and normal tissues, the relationship with overall survival, and the enriched pathways. The MTT assays and Transwell assays were performed to detect the proliferation, migration, and invasion abilities of lung cancer cells after treatments. Western blotting, qRT-PCR, immunohistochemistry, and xenograft models were used to illustrate how CAFs functions in lung cancer progression via exosomes. CAFs-derived exosomes, in which PN1 was higher expressed compared with NFs-derived ones, promoted effectively the proliferation, migration, and invasion of lung cancer cells A549 and H1975. Meanwhile, the expression of PN1 expressed higher in lung cancer tissues compared with normal ones, and was negatively associated with the overall survival rate of lung cancer patients. More importantly, over-expressing or silencing PN1 in A549 and H1975 could also promote or inhibit cell proliferation, migration, and invasion correspondingly. Furthermore, treated with PN1 over-expressed CAFs-derived exosomes, the lung cancer cells proliferation, migration, and invasion varied positively, and accompanied by activation of Toll-like and NF-κB signaling pathways. However, this phenomenon can be reversed by AN-3485, an antagonist of Toll-like pathway. Finally, over-expressing PN1 leads to an accelerated tumor growth by increasing the expression of proliferation biomarker Ki67 and activation of NF-κB signaling pathway in vivo. CAFs promoted lung cancer progression by transferring PN1 and activating Toll-like/NF-κB signaling pathway via exosomes.

Clinicopathological characteristics of mucinous breast cancer: a retrospective analysis of a 6-years study from national cancer center in Vietnam.

To evaluate clinicopathological features in women with mucinous breast cancer (MBC), distinguishing between pure (PMC) and mixed (MMC) subtype. A retrospective analysis of all 358 women with MBC treated at Vietnam National Cancer hospital from June 2015 to December 2020. PMC was defined by ≥ 90% mucinous components. We identified 358 women with MBC (245 PMC and 113 MMC) representing 2.7% of all 13,254 BC patients. The proportions of stage I, II, III and IV were 34.9%, 50.8%, 10.4% and 3.9% respectively. The rate of HER2 overexpression was 12%, and only 1.4% of patients was treated with anti-HER2. 193 patients (53.9%) had chemotherapy, including 55 patients (15.4%) treated in the neoadjuvant setting. Only 3 patients (5.5%) achieved pCR. PMC patients were older (54.4 ± 13.3 vs 51.1 ± 13.1years), had lower Ki67 expression, lower incidence of nodal metastasis (N +) (p values < 0.05). At a median follow-up of 58months, the 5-year overall survival rate of non-metastatic patients was 86.6%. Multivariate analysis showed N + to be the most significant prognostic factor (HR = 3.3; 95%CI 1.5-7.1), followed by T-stage (HR = 2.9; 95%CI 1.4-6.3), HER2 + (HR = 2.5; 95%CI 1.2-5.3) and MMC subtype (HR = 1.9; 95%CI 1.0-3.9). Poor prognostic factors of MBC include high T-stage, N-positivity, HER2 overexpression and MMC subtype. Given the low response rate to neoadjuvant CT, upfront surgery is appropriate for MBC patients.

The 5-year relative survival rate among cancer patients in Henan province of China, 2015-2019

Objective: To analyze the 5-year relative survival rate of cancer in Henan province based on cancer registration data. Methods: Cancer survival data were extracted from the cancer registration database of Henan province with the diagnosis date between January 1, 2010 and December 31, 2019 were included. The closing date of follow-up was set as December 31, 2019. The 5-year relative survival rate of cancer was calculated using the period survival analysis method and the Ederer II method in the R package "periodR", and the interest period was between 2015 and 2019. Results: During the period of 2015-2019, the overall 5-year relative survival rate of cancer patients in Henan province was 43.6%, and after age-standardization, it was 40.2%. The overall 5-year relative survival rate showed the characteristics of higher survival rate in females than males (45.9% vs 34.7%, Z=39.60, P＜0.001) and higher survival rate in urban areas than rural areas (44.9% vs 39.1%, Z=12.97, P＜0.001). The 5-year relative survival rate for cancer patients among children aged 0-14 was 60.2%, and for adults aged 15 and above, it was 43.5%, which was standardized to 40.2% after age adjustment. There are two types of cancers with a standardized 5-year relative survival rate exceeding 70% (thyroid cancer at 82.2% and breast cancer at 71.6%), and four cancers with a rate below 30% (pancreatic cancer at 18.2%, liver cancer at 19.6%, lung cancer at 24.0%, and gallbladder cancer at 26.6%). Conclusion: The cancer 5-year survival rate in Henan Province is lower than that of the national average, indicating the need for continued enhancement of cancer prevention and control measures.

Clinical impact of large genomic explorations at diagnosis in 198 pediatric solid tumors: a monocentric study aiming practical feasibility of precision oncology

IntroductionFaced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy.MethodsA total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics.ResultsOne hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse.ConclusionOur experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse.

UL16‑binding protein 1 is a significant prognostic and diagnostic marker for breast cancer.

The aim of the present study was to investigate the association between UL16 binding protein 1 (ULBP1) and the prognosis of patients with and immune cell infiltration in breast cancer (BRCA). The mRNA data of BRCA and immune-related genes were extracted from The Cancer Genome Atlas and were analyzed using bioinformatics tools. Subsequently, the results obtained by bioinformatics were validated through the collection of clinical patient data at the Zibo Central hospital (Zibo, China). The difference in the expression of the ULBP1 gene between BRCA tissues and normal precancerous tissues was analyzed, followed by validation using immunohistochemistry. By combining clinical data from patients with BRCA, the prognostic and diagnostic significance of the ULBP1 gene in patients with BRCA was analyzed. Gene enrichment analysis was conducted to gain insight into the molecular mechanisms underlying the regulatory role of ULBP1 in BRCA by analyzing its related functions and signaling pathways. Furthermore, single sample gene set enrichment analysis (ssGSEA) and Spearman's correlation analysis were performed to explore the correlation between ULBP1 as a target gene related with tumor immune cell infiltration. The data revealed that ULBP1 is a target gene associated with immunity and the prognosis of patients with BRCA. Patients with BRCA with a high expression of ULBP1 had a poorer prognosis. ULBP1 expression correlated with progesterone receptor expression, estrogen receptor expression and histological type in patients with BRCA; thus, it may serve as an independent predictor for the overall survival rate of patients. Functional enrichment analysis revealed a significant co-expression between ULBP1 and ULBP2, ULBP3, retinoic acid early transcript 1K, as well as a significant enrichment of pathways associated with carcinogenesis and immune suppression. ssGSEA and Spearman's correlation analysis demonstrated significant correlations between ULBP1 expression and tumor immune cells, as well as immune checkpoints. Overall, the present study demonstrated that ULBP1 was associated with BRCA immunity and might serve as a prognostic and diagnostic biomarker for patients with BRCA. In addition, it might also be a potential target for the immunotherapy of BRCA.

ANGIOGENIC FACTORS AS PREDICTORS OF SURVIVAL IN PATIENTS WITH BONE SARCOMAS

Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis. Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas. Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q1–Q3: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q1–Q3: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model. Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p 0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013). Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop

BackgroundClear cell renal cell carcinoma (ccRCC) arises from the renal parenchymal epithelium and is the predominant malignant entity of renal cancer, exhibiting increasing incidence and mortality rates over time. SEC14-like 3 (SEC14L3) has emerged as a compelling target for cancer intervention; nevertheless, the precise clinical implications and molecular underpinnings of SEC14L3 in ccRCC remain elusive.MethodsBy leveraging clinical data and data from the TCGA-ccRCC and GEO datasets, we investigated the association between SEC14L3 expression levels and overall survival rates in ccRCC patients. The biological role and mechanism of SEC14L3 in ccRCC were investigated via in vivo and in vitro experiments. Moreover, siRNA-SEC14L3@PDA@MUC12 nanoparticles (SSPM-NPs) were synthesized and assessed for their therapeutic potential against SEC14L3 through in vivo and in vitro assays.ResultsOur investigation revealed upregulated SEC14L3 expression in ccRCC tissues, and exogenous downregulation of SEC14L3 robustly suppressed the malignant traits of ccRCC cells. Mechanistically, knocking down SEC14L3 facilitated the ubiquitination-mediated degradation of ribosomal protein S3 (RPS3) and augmented IκBα accumulation in ccRCC. This concerted action thwarted the nuclear translocation of P65, thereby abrogating the activation of the nuclear factor kappa B (NFκB) signaling pathway and impeding ccRCC cell proliferation and metastasis. Furthermore, diminished SEC14L3 levels exerted a suppressive effect on NFKB1 expression within the NFκB signaling cascade. NFKB1 functions as a transcriptional regulator capable of binding to the SEC14L3 enhancer and promoter, thereby promoting SEC14L3 expression. Consequently, the inhibition of SEC14L3 expression was further potentiated, thus forming a positive feedback loop. Additionally, we observed that downregulation of SEC14L3 significantly increased the sensitivity of ccRCC cells to sunitinib. The evaluation of SSPM-NPs nanotherapy highlighted its effectiveness in combination with sunitinib for inhibiting ccRCC growth.ConclusionOur findings not only underscore the promise of SEC14L3 as a therapeutic target but also unveil an SEC14L3/RPS3/NFκB positive feedback loop that curtails ccRCC progression. Modulating SEC14L3 expression to engage this positive feedback loop might herald novel avenues for ccRCC treatment.

Machine learning-based model for CD4+ conventional T cell genes to predict survival and immune responses in colorectal cancer

Globally, CRC ranks as a principal cause of mortality, with projections indicating a substantial rise in both incidence and mortality by the year 2040. The immunological responses to cancer heavily rely on the function of CD4Tconv. Despite this critical role, prognostic studies on CRC-related CD4Tconv remain insufficient. In this investigation, transcriptomic and clinical data were sourced from TCGA and GEO. Initially, we pinpointed CD4TGs using single-cell datasets. Prognostic genes were then isolated through univariate Cox regression analysis. Building upon this, 101 machine learning algorithms were employed to devise a novel risk assessment framework, which underwent rigorous validation using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, time-dependent ROC curves, nomograms, and calibration plots. Furthermore, GSEA facilitated the examination of these genes’ potential roles. The RS derived from this model was also analyzed for its implications in the TME, and its potential utility in immunotherapy and chemotherapy contexts. A novel prognostic model was developed, utilizing eight CD4TGs that are significantly linked to the outcomes of patients with CRC. This model’s RS showcased remarkable predictive reliability for the overall survival rates of CRC patients and strongly correlated with malignancy levels. RS serves as an autonomous prognostic indicator, capable of accurately forecasting patient prognoses. Based on the median value of RS, patients were categorized into subgroups of high and low risk. The subgroup with higher risk demonstrated increased immune infiltration and heightened activity of genes associated with immunity. This investigation’s establishment of a CD4TGs risk model introduces novel biomarkers for the clinical evaluation of CRC risks. These biomarkers may enhance therapeutic approaches and, in turn, elevate the clinical outcomes for patients with CRC by facilitating an integrated treatment strategy.

SURGICAL TREATMENT OF RECTAL CANCER WITH PRESERVATION OF THE LEFT COLIC ARTERY AND ICG NAVIGATION

Goal. To analyze the peculiarities of surgical diagnosis of lymphogenic metastasis in patients with colorectal cancer. Generalization of data from Ukrainian and foreign literature, results of randomized studies and meta-analyses. The study is based on the results of observation of 88 patients with colorectal cancer (CRC) of the prospective study group. To analyze the features of surgical diagnostics of lymphogenic metastasis in patients with colorectal cancer. Materials and methods. The results of surgical treatment of 88 patients with rectal cancer were analyzed and systematized. These patients underwent examination and treatment in 2023-2024 at the "Prykarpattian Clinical Oncology Center of the Ivano-Frankivsk Regional Council." The study included patients with stage II-III colorectal cancer (T2-3N0-2M0) without complicated courses. All patients received treatment based on NCCN recommendations. Surgical treatment was performed in standard volume with the removal of all regional lymph node groups and preservation of the left colic artery using real-time lymph node mapping with indocyanine green. All patients were divided into two study groups: Group I included 45 patients who underwent anterior or low anterior resection of the rectum with preservation of the left colic artery. This group was subdivided into two subgroups: Ia – 13 patients who underwent intraoperative indocyanine green injection for real-time lymph node visualization. Ib – 32 patients who did not receive this drug but underwent the same volume of surgery. Group II consisted of 43 patients who underwent anterior or low anterior resection of the rectum with high ligation of the inferior mesenteric artery. This group served as the control group. Results. The main mechanisms of lymphogenic metastasis in colorectal cancer patients in Ivano-Frankivsk were characterized. Literature data on the features of surgical diagnostics of colorectal cancer metastasis were summarized. A review of literature shows the social significance of these studies, as this pathology often leads to patient disability, requiring surgical interventions and further palliative treatment due to the widespread metastasis associated with this disease. The priority task for researchers remains the search for the most effective treatment methods for this pathology, based on randomized studies of colorectal cancer treatment and international protocols. According to the literature, surgical treatment of colorectal cancer remains insufficiently effective at the current stage of oncology. Modern methods offer low 5-year survival rates, emphasizing the need to study factors for individualized treatment. The overall 5-year survival rate for colorectal cancer patients from 2018-2022 was (45.8±2.3)%. The effectiveness of using real-time ICG navigation for lymph node mapping and preservation of the left colic artery in stage II-III (T2-4N1-2M0) rectal cancer patients has been proven. This technique allows for optimal lymphadenectomy, reducing the frequency of surgical complications by 14.7% (p&lt;0.05). Conclusion. Ensuring radical resection of rectal cancer while maximizing blood supply preservation to the anastomosis is the main goal of colorectal surgeons. Over the past two decades, surgical techniques have significantly improved due to advancements in surgical equipment. It is anticipated that surgical technologies will further evolve towards enhancement and individualization in the future. Our procedure serves as an example of modern and personalized rectal cancer surgery.

Efficacy and safety of immunotherapy combined with chemotherapy in patients with ES-SCLC: A systematic review and network meta-analysis of RCTs and RWSs.

To evaluate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), we conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and real-world studies (RWS). By scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta-analysis (NMA). Compared to chemotherapy, the addition of PD-1/PD-L1 inhibitors significantly improves the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3-4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non-elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD-L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy. In ES-SCLC treatment, adding PD-1/PD-L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non-elderly patients, respectively.

Application of artificial intelligence model in pathological staging and prognosis of clear cell renal cell carcinoma

This study aims to develop a deep learning (DL) model based on whole-slide images (WSIs) to predict the pathological stage of clear cell renal cell carcinoma (ccRCC). The histopathological images of 513 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training set and validation set according to the ratio of 8∶2. The CLAM algorithm was used to establish the DL model, and the stability of the model was evaluated in the external validation set. DL features were extracted from the model to construct a prognostic risk model, which was validated in an external dataset. The results showed that the DL model showed excellent prediction ability with an area under the curve (AUC) of 0.875 and an average accuracy score of 0.809, indicating that the model could reliably distinguish ccRCC patients at different stages from histopathological images. In addition, the prognostic risk model constructed by DL characteristics showed that the overall survival rate of patients in the high-risk group was significantly lower than that in the low-risk group (P = 0.003), and AUC values for predicting 1-, 3- and 5-year overall survival rates were 0.68, 0.69 and 0.69, respectively, indicating that the prediction model had high sensitivity and specificity. The results of the validation set are consistent with the above results. Therefore, DL model can accurately predict the pathological stage and prognosis of ccRCC patients, and provide certain reference value for clinical diagnosis.

Machine learning based intratumor heterogeneity signature for predicting prognosis and immunotherapy benefit in stomach adenocarcinoma

Stomach adenocarcinoma (STAD) is a prevalent malignancy that is highly aggressive and heterogeneous. Intratumor heterogeneity (ITH) showed strong link to tumor progression and metastasis. High ITH may promote tumor evolution. An ITH-related signature (IRS) was created using as integrative technique including 10 machine learning methods based on TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets. The relevance of IRS in predicting the advantages of immunotherapy was assessed using a number of prediction scores and three immunotherapy datasets (GSE78220, IMvigor210 and GSE91061). Vitro experiments were performed to verify the biological functions of AKR1B1. The RSF + Enet (alpha = 0.1) projected model was proposed as the ideal IRS because it had the highest average C-index. The IRS demonstrated a strong performance in serving as an independent risk factor for the clinical outcome of STAD patients. It performed exceptionally well in predicting the overall survival rate of STAD patients, as seen by the TCGA cohort’s AUC of 1-, 3-, and 5-year ROC curves, which were 0.689, 0.683, and 0.669, respectively. A low IRS score demonstrated a superior response to immunotherapy, as seen by a lower TIDE score, lower immune escape score, greater TMB score, higher PD1&CTLA4 immunophenoscore, higher response rate, and improved prognosis. Common chemotherapeutic and targeted treatment regimens had lower IC50 values in the group with higher IRS scores. Vitro experiment showed that AKR1B1 was upregulated in STAD and knockdown of AKR1B1 obviously suppressed tumor cell proliferation and migration. The present investigation produced the best IRS for STAD, which may be applied to prognostication, risk stratification, and therapy planning for STAD patients.

Clinical features and prognostic factors of AIDS-associated diffuse large B-cell lymphoma

To explore the general clinical features and treatment outcomes of patients with AIDS-related diffuse large B-cell lymphoma (AIDS-DLBCL) and provide a theoretical basis for diagnosis and treatment, survival prognosis, prevention and management of AIDS-DLBCL patients. AIDS-DLBCL patients who received combined antiretroviral therapy (cART) at Changsha First Hospital from January 2017 to January 2020 were selected in this study. The survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to analyze the association between AIDS-DLBCL specific variables and progression-free survival and overall survival. Correlation analysis was conducted based on the clinical features of the patients. A total of 50 AIDS-DLBCL patients were included. Their median age (Q1, Q3) was 52 (44, 59) years, of whom 46 (92%) were male. About 20 (40%) patients received treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), while 23 patients (46%) received treatment with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Survival curve analysis showed that the 2-year progression-free survival rate and overall survival rate of AIDS-DLBCL patients were 56.9% and 61.6%, respectively. Patients with RCHOP protocol combined with EBV-DNA≥1 000 copies/ml had higher progression-free survival rate (χ2=3.844, P=0.043) and overall survival rate (χ2=4.662, P=0.031) than those with CHOP protocol combined with EBV-DNA≥1 000 copies/ml. A multivariate analysis showed that male (HR=2.70, 95%CI:1.10-6.80), EB viral load≥1 000 copies/ml (HR=1.75, 95%CI:1.12-2.84), HIV-RNA≥200 copies/ml (HR=4.64, 95%CI: 1.73-12.15), ECOG PS score of 2 to 4 points (HR=3.54, 95%CI:1.62-7.33), and international prognostic index (IPI) score of 3 to 5 points (HR=5.21, 95%CI:1.39-20.14) were at a higher risk of disease progression. Patients with EB viral load≥1 000 copies/ml (HR=0.07, 95%CI:0.05-0.93) on the RCHOP regimen had a small risk of disease progression. Males (HR=2.87, 95%CI:1.65-9.17), EB viral load≥1 000 copies/ml (HR=1.61, 95%CI:4.02-9.36), HIV-RNA≥200 copies/ml (HR=1.19, 95%CI:1.58-2.74), ECOG PS score of 2 to 4 (HR=6.42, 95%CI:2.55-14.33), IPI score of 3 to 5 points (HR=2.78, 95%CI:1.41-12.96) had a high risk of mortality. Patients with EB viral load≥1 000 copies/ml (HR=0.24, 95%CI:0.64-0.90) on the RCHOP regimen had a low risk of mortality. In summary, males, ECOG physical status score of 2 to 4 points, IPI score of 3 to 5 points, EB viral load≥1 000 copies/ml and HIV viral load≥200 copies/ml are risk factors affecting progression-free survival and overall survival of AIDS-DLBCL patients. RCHOP regimen combined with EB viral load≥1 000 copies/ml is a protective factor affecting progression-free survival and overall survival in AIDS-DLBCL patients.

DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.

Leveraging programmed cell death signature to predict clinical outcome and immunotherapy benefits in postoperative bladder cancer

Bladder cancer is the fourth most common malignancy in men with poor prognosis. Programmed cell death (PCD) exerts crucial functions in many biological processes and immunotherapy responses of cancers. Cell death signature (CDS) is novel gene signature comprehensively considering the characteristics of 15 patterns of programmed cell death, which could affect the prognosis and immunotherapy benefits of cancer patients. Integrative machine learning procedure including 10 algorithms was conducted to construct a prognostic CDS using TCGA, GSE13507, GSE31684, GSE32984 and GSE48276 datasets. Immunophenoscore, intratumor heterogeneity (ITH), tumor immune dysfunction and exclusion (TIDE) score and five immunotherapy cohorts were used to evaluate the predictive value of CDS in immunotherapy response. The prognostic CDS constructed by StepCox[backward] + Ridge algorithms was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting overall survival of bladder cancer patients with the AUCs at 3-year, 5-year, and 7-year ROC of 0.740, 0.763 and 0.820 in TCGA cohort. Moreover, CDS score acted as an independent risk factor for overall survival rate of bladder cancer patients. Low CDS score had a higher abundance of immuno-activated cells, higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score, lower immune escape score, lower ITH score, lower cancer-related hallmarks score in bladder cancer. The CDS score was higher in non-responders in pan-cancer patients receiving immunotherapy. Our study constructed a novel prognostic CDS, which could serve as an indicator for predicting the prognosis in postoperative bladder cancer cases and immunotherapy benefits in pan-cancer. Low CDS score indicated a better prognosis and immunotherapy benefits.

The Prognostic Significance of CTSV Expression in Patients with Hepatocellular Carcinoma.

Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker. This study collected tumor and peritumoral archived specimens from 180HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV. In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC. CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.

Design of an emergency medical information system for mass gatherings

BackgroundThe frequency of mass gatherings is increasing. Such events often involve many people and carry the risk of mass casualty incidents, which require substantial medical resources from various healthcare institutions. The current medical system, while meeting daily needs, struggles to address the demand for a high volume of emergency resources and real-time data exchange. ObjectiveThe aim of this study was to develop an emergency medical information system for mass gatherings. MethodsWe developed an emergency medical information system for mass gatherings. Based on a unified prehospital and intrahospital emergency data exchange protocol, we can directly standardize medical information data and provide data support for the evacuation decision support algorithms of multiple institutions. Wearable devices, vehicle-mounted devices, video calling systems and surveillance systems are connected to capture real-time scenes. ResultsWe constructed the system via mobile applications and online platforms and deployed it in 3 hospitals, 5 ambulances and 17 on-site medical locations. We constructed a set of electronic medical records covering the whole first aid process according to the basic principles of first aid. The simulation results show that the proposed algorithm is suitable for mass gatherings. The overall survival rate of patients can be improved by 5 %, and the average evacuation efficiency of patients can be improved by 50 %. Furthermore, in a real-world environment, this method can ensure patient survival and achieve good convergence. ConclusionsOur system is capable of providing robust medical information support for emergency medical services during large-scale assembly events, ensuring a visualized full-process emergency response and decision-making for the diversion and subsequent transport of a large patient population.

Efficacy and Safety of Ixazomib Combined with Thalidomide and Dexamethasone in Treatment of Multiple Myeloma

To investigate the efficacy and safety of ixazomib combined with thalidomide and dexamethasone in the treatment of multiple myeloma (MM). The clinical data of 60 MM patients admitted to our center from January 2019 to June 2022 were analyzed retrospectively, including 43 newly diagnosed patients and 17 patients with recurrence and progression. All patients were treated with ixazomib combined with thalidomide and dexamethasone, and completed 2 to 7 treatment cycles. The overall response rate (ORR) of all patients was 98.3%. Among them, 53 patients completed 4 treatment cycles, and the ORR was 86.8%. Seventeen patients completed the whole treatment cycle, with curative effect reaching 88.2% achieving very good partial response and above, and 52.9% achieving complete response and above. Albumin and β2-microglobulin of all patients had been improved rapidly after treatment. The deadline was August 31, 2022. The median follow-up time was 14(3-24) months, and overall survival (OS) rate was 86.67%. The OS rate of patients with recurrence and progression was significantly lower than that of newly diagnosed patients (P < 0.05). The most common adverse reaction of hematology was lymphopenia (53.3%), followed by anemia (33.3%). The most common non-hematological adverse reaction was fatigue (68.33%), followed by peripheral neuropathy (31.67%). Ixazomib combined with thalidomide and dexamethasone is effective in the treatment of MM, with good short-term efficacy, survival and safety. However, its long-term efficacy needs further observation.

Values of Serum Ferritin, Folic Acid and Vitamin B12 in Treatment of Multiple Myeloma with Bortezomib Combined with Chemotherapy

To investigate the value of serum ferritin, folic acid and vitamin B12 in the treatment of multiple myeloma (MM) with bortezomib combined with chemotherapy. Clinical data of 40 MM patients admitted to our hospital from January 2020 to August 2022 and 40 hematology outpatients during the same period were reviewed. All MM patients were treated with bortezomib combined with chemotherapy. The diagnostic efficacy of serum ferritin, folic acid and vitamin B12 on MM was analyzed by ROC curve. The changes of serum ferritin, folic acid and vitamin B12 in MM patients before and after treatment were compared. According to the mean values of serum ferritin, folic acid and vitamin B12, patients were divided into high and low expression groups, and the survival of patients between the groups was compared. Before treatment, the levels of serum ferritin and vitamin B12 in MM patients were significantly higher than those in control group, while folic acid was lower (all P <0.001). The area under the curve (AUC) of MM patients diagnosed with ferritin, folic acid and vitamin B12 were 0.928, 0.843 and 0.867, the specificity was 100%, 67.50% and 72.50%, and the sensitivity was 80.00%, 95.00% and 87.50%, respectively. After 4 cycles of chemotherapy, there were 9 cases of complete remission (CR), 19 cases of very good partial remission (VGPR), 6 cases of PR, 4 cases of stable disease (SD) and 2 cases of progression disease (PD) in 40 MM patients. In CR group, ferritin and vitamin B12 decreased but folic acid increased after treatment compared with before treatment (all P < 0.05). The overall survival (OS) rates of patients in low expression group of ferritin and vitamin B12 were significantly higher than those in high expression group (both P < 0.01). The OS rate of patients in high expression group of folic acid was significantly higher than that in low expression group (P < 0.01). Cox regression analysis showed that ferritin was an independent prognostic factor for MM patients (HR=8.850, 95%CI : 2.267-34.553, P =0.002). Serum ferritin, folic acid and vitamin B12 have some auxiliary value in the diagnosis and efficacy evaluation of MM, and ferritin is an independent prognostic factor for MM.