Prognostic Factor For Patient Survival Research Articles

Prognostic significance of microsatellite instability in patients with resectable gastric cancer

BackgroundMicrosatellite instability (MSI) gastric cancer (GC) generally has a better prognosis than microsatellite-stable (MSS) GC and has been associated with nonsurvival benefit with the addition of chemotherapy (CMT) compared with surgery alone. However, patients with MSI have distinct clinicopathological characteristics. This study aimed to compare the survival outcomes between patients with MSI GC and those with MSS GC. In addition, this study analyzed the survival outcomes of patients with MSI GC who received CMT. MethodsThis study reviewed all patients with GC who underwent curative gastrectomy. Patients were divided into MSI group and the MSS group. Propensity score matching (PSM) was used to match clinicopathological factors. ResultsAmong the 378 patients enrolled, 78 (20.6%) had MSI. Older age (P < .001), subtotal gastrectomy (P = .008), pN0 (P = .020), and earlier pTNM stage (P = .012) were associated with MSI GC. Survival analysis showed better disease-free survival (DFS) and overall survival (OS) of patients in the MSI group (P = .012 and P = .019, respectively). After PSM, 78 patients were matched to each group. All variables assigned to the scores were well matched, and both groups became equivalent. After the matching, the differences in DFS and OS according to MSI/MSS status were estimated to be larger than before (DFS: 63.3% vs 41.4%; P = .002; OS: 65.8% vs 42.5%; P = .002). Regarding patients referred for CMT, there was no difference in DFS and OS between patients with MSI GC who underwent CMT and those who underwent surgery alone (P = .255 and P = .178, respectively). ConclusionEven after controlling for clinicopathological characteristics, MSI was identified as a prognostic factor for patient survival. MSI GC showed no significant survival benefit with the addition of CMT.

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study

BackgroundMost gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan.MethodsPatients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of survival.ResultsA total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01–14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39–10.89).ConclusionsWe present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Identification of Risk Factors for Relapse in Childhood Leukemia Using Penalized Semi-parametric Mixture Cure Competing Risks Model.

Leukemia is the most common childhood malignancy. Identifying prognostic factors of patient survival and relapse using more reliable statistical models instead of traditional variable selection methods such as stepwise regression is of great importance. The present study aimed to apply a penalized semi-parametric mixture cure model to identify the prognostic factors affecting short-term and long-term survival of childhood leukemia in the presence of competing risks. The outcome of interest in this study was time to relapse. Study Design: A retrospective cohort study. A total of 178 patients (0‒15 years old) with leukemia participated in this study (September 1997 to September 2016, followed up to June 2021) at Golestan University of Medical Sciences, Iran. Demographic, clinical, and laboratory data were collected, and then a penalized semi-parametric mixture cure competing risk model with smoothly clipped absolute deviation (SCAD) and least absolute shrinkage and selection operator (LASSO) regularizations was used to analyze the data. Important prognostic factors of relapse patients selected by the SCAD regularization method were platelets (150000‒400000 vs.>400000; odds ratio=0.31) in the cure part and type of leukemia (ALL vs. AML, hazard ratio (HR)=0.08), mediastinal tumor (yes vs. no, HR=16.28), splenomegaly (yes vs. no; HR=2.94), in the latency part. In addition, significant prognostic factors of death identified by the SCAD regularization method included white blood cells (<4000 vs.>11000, HR=0.25) and rheumatoid arthritis signs (yes vs. no, HR=5.75) in the latency part. Several laboratory factors and clinical side effects were associated with relapse and death, which can be beneficial in treating the disease and predicting relapse and death time.

Knock out of ELAVL1 affects steroid synthesis in adrenocortical carcinoma cell line NCI-H295R and leads to a less malignant phenotype

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal gland. With a 5-year-survival rate below 50% and no curative treatment options in advanced stages new therapeutic options in ACC are needed. Analyzing the ACC cohort of the cancer genome atlas we found a significant negative correlation of the expression level of a gene called Embryonic Lethal Abnormal Vision Like 1 (ELAVL1) and ACC patient survival. ELAVL1 has been described to be unfavorable in a lot of different tumor entities, but its function in ACC progression is still unknown. Methods: To evaluate the function of ELAVL1 in ACC progression we performed a CRISPR/Cas9 mediated knock out (KO) of the ELAVL1 gene in the ACC cell line NCI-H295R. The KO was confirmed on DNA level via Sanger sequencing and on protein level via immunofluorescence and western blot. Transcriptome changes were analyzed by next generation RNA sequencing (NGS). To characterize changes in cell function we performed soft agar colony forming assays and evaluated changes in steroid production via mass spectrometry. Results: Via CRISPR/Cas9 we knocked out ELAVL1 in NCI-H295R cells. NGS data showed 6926 significantly deregulated genes in ELAVL1-KO cells compared to control cells. There was an upregulation of 3468 genes, while 3458 genes showed a lower expression in ELAVL1 KO cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed a significant upregulation of 29 genes associated with aldosterone synthesis and a significant downregulation of 87 genes associated with pathways in cancer. Analyzing cell function via soft agar colony forming assays an impaired colony forming ability in ELAVL1 KO cells was seen. Furthermore, we could prove significant changes in steroid production. ELAVL1 KO led to an inhibition of androgen and glucocorticoid synthesis and an enhancement in mineralocorticoid synthesis. These changes could not only be proven by measuring steroid concentrations in cell culture supernatants, but also by NGS showing a downregulation of the genes CYP17A1 and CYP11B1 and an upregulation of CYP21A2 and CYP11B2. Conclusion: Our study showed that ELAVL1 affects the regulation of around 7000 genes in the ACC cell line NCI-H295R. Especially the inhibition of glucocorticoid synthesis shows that ELAVL1 may be a new target for therapeutic approaches in ACC treatment since hypercortisolism is one of the main symptoms in ACC and a negative prognostic factor for patient survival. The authors have nothing to disclose. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein–protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Abstract 1053: The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression

Abstract Glioblastoma (GB), IDH-wildtype, is the most common and aggressive high-grade primary malignant brain tumor with extremely poor outcome. Although the use of immune checkpoint inhibitors (ICIs) in GB has shown disappointing results, the identification of a small subgroup of responders underpins the role of the intratumoral immune contexture, in particular tumour-infiltrating lymphocytes (TILs), in determining disease outcome. This study aims to define the features of TIL subpopulations correlating with GB prognosis, and to establish in parallel the predictive roles of peripheral T cell subsets. A single cohort observational study, including patients undergoing GB resection and standard therapeutic and follow-up approaches in Neuro-Oncology, was conducted. Of the 45 patients, histologically confirmed WHO grade 4, 26 had MGMT promoter methylation (60.0%), 24 were male (53.3%) and the median age of young patients (≤63 years) vs elderly patients (&amp;gt;63 years) was 57 vs 71, respectively. Predictors of OS were KPS (≥70 vs &amp;lt;70: 14.7 vs 7.5 months, p=0.0007) and GTR (GTR vs non-GRT: 15 vs 9 months, p=0.004) whereas patients with methylated MGMT promoter had non-significant longer median OS compared to those with unmethylated promoter (14.5 vs 10.5 months). Patients were characterized for the expression of lineage, differentiation, memory, activation, and inhibition markers on intratumoral and peripheral CD4+ and CD8+ T cell subpopulations, and the correlation of an array of CD4+ and CD8+ T cell subsets with OS or PFS was evaluated by multiparametric flow cytometry and uni/multivariate analyses. Intratumoral immune infiltrate was positively associated with CD8+CD103+ tissue-resident memory T cells (Trm), and in particular with CD8+CD103+ Trm expressing PD1 and TIM3 rather than CD4+ Trm. Low CD8+CD103+PD1+ Trm resulted significantly associated with better OS and PFS (p=0.02 and 0.0031, respectively) and even higher significant was the correlation with better OS and PFS of low CD8+CD103+TIM3+ Trm (p=0.0002 and 0.0033, respectively) and CD8+CD103+PD1+TIM3+ Trm (p&amp;lt;0.0001, both). On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios - HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). Moreover, CD8+CD103+ Trm subpopulations resulted age-related predictors for GB survival. Consistent with this finding, in vitro PD1 and TIM3 blockade released the capability of intratumoral T cells to produce the effector cytokines IFN-γ and TNF-α, and the cytotoxic factor GrzB. Conversely, T cells expressing PD1 and TIM3 of peripheral blood did not show any prognostic significance. In conclusion, low frequency of Trm expressing PD1 or TIM3 or both markers defined TIL subsets as independent positive prognostic factors for patient survival. Citation Format: Lucia Gabriele, Giulia Romagnoli, Quintino Giorgio D'Alessandris, Imerio Capone, Andrea Tavilla, Irene Canini, Caterina Lapenta, Mariachiara Buccarelli, Martina Giordano, Valentina Tirelli, Massimo Sanchez, Alessandra Fragale, Stefano Giannetti, Rina Di Bonaventura, Liverana Lauretti, Mauro Biffoni, Lucia Ricci-Vitiani, Roberto Pallini. The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression [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 1053.

Survival of Patients With Primary Cutaneous Melanoma (Stages 0-IIА and IIB-IIC), Depending on the Presence of the &lt;i&gt;BRAF&lt;/i&gt; Mutation in the Tumor and Surgical Treatment Option

Background: Cutaneous melanoma is an extremely aggressive disease with an unpredictable prognosis. Even among patients with similar tumor parameters and extent of surgical treatment, survival may vary. The extent of surgical resection of primary cutaneous melanoma is well-established, and a BRAF mutation in the tumor is an unfavorable prognostic factor for patient survival. The mutation presence is mainly used as a marker for prescribing targeted therapy. The impact of the extent of surgery and the method for restoring a tissue defect on survival of patients with similar stages remains unexplored. The impact of the BRAF mutation in the tumor on survival of patients with cutaneous melanoma depending on the surgery method has also not been studied. We analyzed the surgical treatment outcomes of 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) who were found to have the BRAF mutation and underwent different extents of tumor excision with closure of the surgical tissue defect.Objective: To analyze the impact of the BRAF mutation in the tumor on 5-year survival of patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC), depending on the extent of surgery and the method of replacing the tissue defect.Materials and methods: We used data from 221 patients with primary cutaneous melanoma (stages 0-IIA and IIB-IIC) and assessed their BRAF mutation status, extent of tumor excision, and method of closing the tissue defect. The patients were divided into 2 groups: the main group (wide excision of the tumor and plastic replacement of the tissue defect) and the comparison group (standard margin and linear closure of the tissue defect). After surgery, all the patients underwent tumor analysis for the BRAF p.V600E/K mutation using real-time PCR. DNA was isolated using the cobas® DNA Sample Preparation Kit on a cobas® z 480 analyzer. We used the following statistical methods: frequency analysis, z test to check the equality, and Kaplan-Meier survival analysis and such software as MedCalc 12.5 (1993-2013, MedCalc Software) and SPSS 26 (IBM Corp, 2019, IBM SPSS Statistics for Windows, Armonk, NY, USA). Results: Wide excision of primary cutaneous melanoma (stages 0-IIA and IIB-IIC) was found to increase 5-year progression-free survival in patients with subsequent plastic replacement of the tissue defect compared with patients with standard margin and linear closure of the tissue defect and 5-year overall survival in patients with stage 0-IIA melanoma. In patients with 0-IIA stage melanoma and positive BRAF mutation test results, wide excision with reconstructive and plastic defect closure improved the 5-year progression-free survival. Conclusions: The 5-year progression-free survival and 5-year overall survival increased by 20.9% (P = .005) and 13.0% (P = .031), respectively, in patients who underwent wide excision of primary cutaneous melanoma followed by plastic replacement of the tissue defect compared with patients with standard excision of primary tumors and linear closure of the tissue defect. The 5-year progression-free survival increased by 23.7% (P = .017) in patients with stage IIB-IIC melanoma, regardless of the BRAF mutation. In patients with 0-IIa stage melanoma and positive BRAF mutation test results who underwent wide excision, the 5-year progression-free survival increased by 20.7% (P = .047) compared with patients who underwent tumor excision with a standard margin.

Retrospective study of combined pelvic exenteration in the treatment of primary and recurrent pelvic malignant tumors.

Pelvic malignant tumors often originate in the rectum, bladder, uterus, and other organs. In patients with locally advanced tumours in the presence of direct invasion of one or more organs, negative tumor resection margin (R0) resection can be very beneficial to patient survival if it can be performed. As a multidisciplinary and high-risk surgical method, the pelvic exenteration (PE) procedure has only been reported in a few medical centres internationally. We retrospectively analyzed the clinical data of patients who had undergone PE surgery in our hospital, in order to provide ideas for the best treatment of patients with pelvic malignant tumors. A retrospective analysis was conducted of 59 patients with pelvic malignant tumors admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to July 2021, all of whom received PE surgery. They were divided into two groups according to the location of the disease: the rectal cancer group (n=40) and the cervical cancer group (n=19). Statistical analysis was performed on the baseline and follow-up data of the two groups of patients. (I) Patient baseline data. Compared to the rectal cancer group, more patients in the cervical cancer group received preoperative radiotherapy and chemotherapy (P=0.013), and had a lower R0 resection rate (P=0.037). Postoperative complications in patients with rectal cancer and cervical cancer were 27.5% and 47.3%, respectively. (II) Patient survival analysis after PE surgery. The 5-year survival rate was 36.6% in the rectal cancer group and 25.3% in the cervical cancer group. In the rectal cancer group, for the primary tumor, if there was no lymph node metastasis or no postoperative complications in the postoperative pathology, the patient had a good survival prognosis. Univariate analysis showed that recurrent rectal cancer, postoperative lymph node metastasis, postoperative complications, and microsatellite stability (MSS) were significant predictors of poor survival outcomes. Multivariate analysis showed that lymph node metastasis and postoperative complications were independent prognostic factors for patient survival. PE is a viable option for pelvic malignancies; aggressive radical resection of lesions and reduced postoperative complications can effectively improve patient outcomes.

Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer

Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC.

A novel NR4A2-HuR axis promotes pancreatic cancer growth and tumorigenesis that is inhibited by NR4A2 antagonists.

Pancreatic ductal adenocarcinoma (PDAC) patients' express higher levels of the orphan Nuclear Receptor 4A2 (NR4A2, NURR1) compared to normal pancreas and NR4A2 is a prognostic factor for patient survival. Knockdown of NR4A2 by RNA interference (RNAi) inhibited cell proliferation, invasion, and migration. RNA sequencing performed in NR4A2(+/+) and NR4A2(-/-) MiaPaCa2 cells demonstrated that NR4A2 played a significant role in cellular metabolism. Human antigen R (HuR) and isocitrate dehydrogenase 1 (IDH1) were identified as NR4A2 target genes. HuR is a pro-oncogenic RNA binding protein and silencing of HuR by RNAi significantly downregulated expression of NR4A2. Expression of HuR and IDH1 were significantly downregulated after treatment with NR4A2 inverse agonist, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl)methane resulting in significant inhibition of tumor growth in an athymic nude mouse xenograft model. This study demonstrates that NR4A2 and HuR regulate genes and signaling pathways that enhance tumorigenesis and targeting NR4A2 and HuR expression with an NR4A2 inverse agonist represents a novel regimen for treating PDAC.

MiR-1182-mediated ALDH3A2 inhibition affects lipid metabolism and progression in ccRCC by activating the PI3K-AKT pathway

In clear cell renal cell carcinoma (ccRCC), dysregulated lipid metabolism plays a pivotal role in tumor initiation and progression. This study delves into the unexplored landscape of Dysregulated Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) in ccRCC. Using a combination of "fatty acid metabolism" dataset analysis and differentially expressed genes (DEGs) derived from Gene Expression Omnibus (GEO) database, potential metabolic regulators in ccRCC were identified. Subsequent investigations utilizing public databases, clinical samples, and in vitro experiments revealed that ALDH3A2 was down-regulated in ccRCC, mediated by miR-1182, highlighting its role as an independent prognostic factor for patient survival. Functionally, ALDH3A2 exhibited tumor-suppressive properties, impacting ccRCC cell phenotypes and influencing epithelial-mesenchymal transition. Mechanistically, silencing ALDH3A2 promoted lipid accumulation in ccRCC cells by activating the PI3K-AKT pathway, thereby promoting tumor progression. These findings shed light on the critical role of the miR-1182/ALDH3A2 axis in ccRCC tumorigenesis, emphasizing the potential for targeting lipid metabolism as a promising anti-cancer strategy.

Evaluation of the Clinical Efficacy of Intensity-Modulated Radiotherapy Combined with Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma with Extrahepatic Oligometastasis and Prognostic Factors for Patient Survival.

To investigate the clinical efficacy of intensity-modulated radiotherapy (IMRT) combined with transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with extrahepatic oligometastasis and the prognosis of patients receiving this treatment. Twenty-one HCC patients with extrahepatic oligometastasis were retrospectively analyzed; seven patients received IMRT only, and 14 received IMRT plus TACE. TACE treatment was administered before IMRT (50 mg epirubicin, oxaliplatin 100 mg, and mitomycin 10 mg). The short-term efficacy of this treatment and patient prognosis were evaluated. Complete response (CR) and partial response (PR) in the intrahepatic region were achieved in three and 14 patients, respectively. The objective response rate (ORR) approached 81%. CR and PR were achieved in six and 10 patients with extrahepatic metastases, respectively, for an ORR of 100%. Pain was completely relieved in all patients with bone metastases. The median overall survival (OS) and progression-free survival (PFS) were 21 months and 9.1 months, respectively. The 1-year PFS rate was 43%, and the 1-, 2-, 3-, and 4-year OS rates were 83%, 35%, 9%, and 4%, respectively. Univariate analysis showed that the prognostic factors for patient survival included Child-Pugh class, vascular thrombus, Karnofsky performance status (KPS), radiotherapy dose, ascites, combination therapy, and pattern of progression. Multivariate analysis showed that vascular thrombus, combination therapy, and pattern of failure were prognostic factors for PFS, and the KPS was the only prognostic factor for OS. No grade 3-4 adverse reactions were observed. IMRT combined with TACE is safe and feasible without major toxicities for the treatment of advanced HCC patients with extrahepatic oligometastasis and results in excellent objective efficacy and a potential survival benefit. The KPS is the only predictive factor for OS. This approach is expected to be a useful palliative option for selected HCC patients with extrahepatic metastases.

Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance

While we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignancies. One explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene, with two being protein-coding. Here, we analysed the expression of the latter across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with clinical features. This revealed the expression of RSK4 isoforms 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that upregulation of either isoform can equally be associated with good or bad prognosis depending on the cancer type, and changes in the expression ratio of isoforms fail to predict clinical outcome. Hence, differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers, and further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase.

Prognostic values of stromal tumor-infiltrating lymphocytes and lymphocyte-activation gene-3 in advanced gastric adenocarcinoma

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.

Correlative effect between sac regression and patient longevity following endovascular solution for abdominal aortic aneurysms: an international analysis.

Since the introduction of endovascular aortic repair (EVAR) it has become the mainstay treatment for abdominal aortic aneurysms. Several EVAR devices exist commercially, yet, the Terumo Aortic Fenestrated Anaconda™ endograft has demonstrated outstanding results. Evidence in the literature suggests that sac regression could be linked to patient survival and longevity. The main scope of this study is to evaluate sac regression and survival achieved using the Fenestrated Anaconda™ endograft and to discuss relevant literature. The current study represents a nine-year cross-sectional international analysis of custom-made Fenestrated Anaconda™ device. For the statistical analysis, SPSS 28 for Windows and R were utilised. Pearson chi-square analysis was used to assess differences in cumulative distribution frequencies between select variables. Statistical significance for all two-tailed tests was set at p < 0.05. A total of 5,058 patients received the Fenestrated Anaconda™ in this study, either due to unsuitable/complex anatomy for competitor devices (n = 3,891) or based on surgeon preference (n = 1,167). A sac regression of 0-30% was observed in 4,772 (94.3%) over the first four years post-EVAR. Here, 99.6% of patients receiving the Fenestrated Anaconda™ due to unsuitable/complex anatomy for competitor devices and 76.8% based on surgeon preference had 0-30% sac regression. During years 5-9 of follow-up, all patients had 20-45% sac regression. Patient survival during the first six years post-EVAR was 100% but dropped to 77.1% in years 7-9. Survival differed between categorical patient subsets based on the indication. The Fenestrated Anaconda™ has been proven to be a highly effective EVAR endograft. Evidence in the literature clearly demonstrates that sac regression is an accurate prognostic factor for patient survival and longevity.

P02.04.A Preoperative neutrophil, thrombocyte and monocyte to lymphocyte ratios as independent prognostic factors for patient survival in WHO 2021 glioblastoma multiforme

Abstract Background Glioblastoma (GBM) is the most common malignant primary central nervous system (CNS) tumor. It is a fast-growing and extremely aggressive malignancy with a short postoperative survival time of little more than a year. The tumor-immune system interactions are complex and can be measured as local phenomena - e.g., tumor-infiltrating lymphocytes, or as systemic events - e.g., lymphopenia, neutropenia, etc. with cell numbers allowing for estimation of the type of immune reaction against the tumor. Material and Methods A retrospective non-clinical approach was utilized for the means of the study. Patients with a histologically and molecular verified GBM, corresponding to the guidelines of 2021 WHO CNS tumor classification, diagnosed in a three-year interval (February 2018-2021) in a single tertiary healthcare institution were included. Patients with infectious, inflammatory, autoimmune, and hematological diseases, as well as those with malignancy in another location, were excluded. Data regarding patient demographics, and preoperative peripheral blood cell counts (neutrophils, platelets, and monocytes in a ratio to lymphocytes) were compared with postoperative patient survival. Preoperative ratios were calculated as absolute values. For cutoff values we used generally accepted ones - &amp;gt;4 for neutrophil to lymphocyte (NLR), &amp;gt;200 for thrombocyte to lymphocyte (TLR), and &amp;gt;0.25 for monocyte to lymphocyte ratios (MLR). Results were statistically analyzed with MedCalc version 19.7.1 and the Kaplan-Meier method. Results A total of 22 patients fit the established criteria, with a male to female ratio of 2.14:1, mean age of 66.23 years, and mean survival of 255.72 days (8.04 months, range 24-801 days). Eight patients had an elevation of NLR and five of PLR, with no statistical correlation to survival. Six patients had an increase in MLR with a statistically significant (p=0.0044) shorter postoperative survival. Synergic increase in NLR and PLR did not show significance, while synergic increase with MLR showed no added benefit, as did comparison within MGMT promoter methylation groups. Conclusion Elevation in NLR, PLR, and MLR is a good independent prognostic marker for postoperative patient survival in histologically and mutationally verified GBM. Acknowledgments * contributed equally to the work and should be considered co-first authors.Financing: Medical University - Varna Scientific Fund, grant number 19010 and National scientific fund - young researchers (Republic of Bulgaria) grant number 2990/07.06.2021 Ethical approval: Medical University - Varna committee on scientific ethics approval protocol number 93/21.05.2020

211.8: Impact of Sarcopenia Using Anterior Thigh Skeletal Muscle Index on Clinical Outcomes in the Liver Transplant Recipient

Backgrounds: Sarcopenia is defined as loss of skeletal muscle strength, mass, and function. It has been reported as a significant risk factor for outcomes after Liver transplantation (LT) as well as waitlist mortality in end-stage liver disease patients. Although there are various imaging modalities and measurement methods for diagnosing sarcopenia, the gold standard is not clear. The purpose of this study is to analyze the effect of sarcopenia on outcome in LT patients using previously known third lumbar (L3)-skeletal muscle index (SMI) cut-off values and newly calculated anterior thigh (AT)-SMI cut-off values. Method: Three hundred forty-one patients who underwent living and deceased donor liver transplantation in our center from Jan 2018 to Dec 2020 were analyzed. L3-SMI and AT-SMI were obtained by measuring preoperative computed tomography scans with semiautomatic software. For L3-SMI, the cut-off values reported in other previous studies were applied (42 cm2/m2 in males, 38 cm2/m2 in females). For AT-SMI, the optimal cut-off value was obtained by the ROC curve for sarcopenia. Results: The prevalence of sarcopenia diagnosed by L3-SMI was 29.9 % (102/ 341) and by AT-SMI was 35.5 % (121/ 341) in our cohort. The cut-off values of AT-SMI obtained by ROC curve were 12.6 cm2/m2 for female (AUC = 0.915, P < 0.001) and 14.2 cm2/m2 for male (AUC = 0.882, P < 0.001). Patient and graft survival rates in the sarcopenia group by AT-SMI were significantly lower than in the non-sarcopenia group (P < 0.001, P < 0.001). AT-SMI was identified as one of the independent prognostic factors in patient survival in multivariable cox analysis, whereas L3-SMI was not (HR, 4.462; 95 % CI, 1.792 – 11.106; P = 0.001). It was also confirmed by ROC curve analysis that AT-SMI was more highly correlated than L3-SMI for patient survival (P = 0.005). Conclusion: Both the L3-SMI and AT-SMI-induced sarcopenia group had a significantly lower patient and graft survival than the group without sarcopenia. However, AT-SMI was identified as an independent prognostic factor for patient survival and was more correlated with patient survival than L3-SMI. This means that AT-SMI may be a better option than L3-SMI for the evaluation of CT-based sarcopenia in LT recipients.

Dynactin 2 acts as an oncogene in hepatocellular carcinoma through promoting cell cycle progression

BackgroundDynactin (DCTN) can activate cytoplasmic dynein and drive intracellular organelle transport containing six family members (DCTN1 to DCTN6). The DCTN family has been studied as cancer-related genes or biomarkers in various cancers. Nevertheless, in hepatocellular carcinoma (HCC), the functions and prognostic roles of the DCTN family have been unexplored. MethodsWe evaluated the diagnostic and survival effects of DCTN subunits in HCC through bioinformatics analysis and validated the results of bioinformatics by our data to address this problem. ResultsThe results of bioinformatics analysis found that DCTN2 was a significant prognostic factor in HCC, and high-level DCTN2 can predict poor patient survival in HCC. Cox regression analysis also suggested that DCTN2 (hazard ratio = 1.748, 95% confidence interval 1.190–2.568, P = 0.004) is an independent prognostic factor for patient survival. Western blot and quantitative reverse transcription-polymerase chain reaction assays confirmed that the protein and mRNA expression levels of DCTN2 were upregulated in HCC cell lines. The proliferation, invasion, and migration were decreased and cell apoptosis was enhanced after DCTN2 was knocked down in Huh7 and Hep3B cells. DCTN2 promoted the cell cycle progression through regulating the expression of cell cycle regulatory proteins cyclin-dependent kinase 4, Cyclin D1, and p21. ConclusionsWe propose that DCTN2 can serve as a prognostic marker for HCC. DCTN2 acts as an oncogene and promotes the cell cycle progression through the G1/S phase-related signaling pathway.

The Role of Preoperative Neutrophil, Platelet, and Monocyte to Lymphocyte Ratios as Independent Prognostic Factors for Patient Survival in WHO 2021 Glioblastoma: A Single-Center Retrospective Study.

IntroductionsImmuno-oncology is a rapidly developing field wherein tumor-immune system interactions can be harnessed for diagnostics. Herein, we set out to establish the role of the immune system response, as measured by preoperative neutrophil, platelet, and monocyte to lymphocyte ratios (NLR, PLR, and MLR) as prognostic markers for patient survival based on the newly defined criteria for glioblastoma (GBM).Materials and methodsThe study included patients diagnosed with GBM at a four-year interval. Exclusion criteria were patients subject to reoperation in the time period; tumors in more than one system; a history of hematological and autoimmune diseases; and cases with infectious or other inflammatory conditions. Data regarding patient demographics and preoperative blood counts were pulled from patient records and compared to postoperative survival.ResultsA total of 22 patients fit the established criteria, with a male to female ratio of 2.14:1, a mean age of 66.23 years, and a mean survival of 255.72 days (8.04 months, range 24-801 days). Eight patients had an elevation of NLR and five of PLR, with no statistical correlation to survival. Six patients had an increase in MLR with a statistically significant (p=0.0044) shorter postoperative survival. Synergic increases in NLR and PLR did not show significance, while synergic increases with MLR showed no added benefit.ConclusionPreoperative MLR, but not NLR or PLR, is a promising independent biomarker for patient survival in GBM. It is suggested that elevations in these ratios directly correlate to tumor biological potential.

Identification of Tumor-Suppressive miR-30e-3p Targets: Involvement of SERPINE1 in the Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma.

Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenger strand of pre-miR-30e). We addressed target genes controlled by miR-30e-3p that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of miR-30e-3p attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of miR-30e-3p targets revealed that 11 genes (ADA, CPNE8, C14orf126, ERGIC2, HMGA2, PLS3, PSMD10, RALB, SERPINE1, SFXN1, and TMEM87B) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (p < 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, SERPINE1 was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, p < 0.05). Aberrant expression of SERPINE1 was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting SERPINE1 expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of SERPINE1 expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.