Multivariate Cox Regression Test Research Articles

Prognostic value of long noncoding RNA LINC00924 in lung adenocarcinoma and its regulatory effect on tumor progression.

Long non-coding RNAs (lncRNAs) have been used in the study of tumor biomarkers in recent years. However, the prognostic role of lncRNA LINC00924 (LINC00924) in lung adenocarcinoma (LUAD) has not yet been concluded. Therefore, this study investigates the prognostic value of LINC00924 in LUAD and its regulatory effect on tumor progression. The LUAD tissues and adjacent normal tissues of 128 subjects were extracted, and the expressions of LINC00924 and miR-196a-5p in tissues and cells were detected by RT-qPCR. The prognostic value of LINC00924 in LUAD patients was obtained by Kaplan-Meier analysis and multivariate Cox regression test. The cell counting kit-8 (CCK-8) and Transwell assay were used to detect the effect of overexpression LINC00924 on LUAD cells. In LUAD tissues and cells, LINC00924 expression was down-regulated and miR-196a-5p expression was up-regulated compared with the normal control group. High expression of LINC00924 inhibited the proliferation level, migration ability and invasion situation of LUAD cells, which was more conducive to the survival and prognosis of LUAD patients. Bioinformatics studies indicated that overexpression of LINC00924 inhibited the development of LUAD by targeting miR-196a-5p, while miR-196a-5p mimic effectively weakened the inhibition. LINC00924 sponges of miR-196a-5p may be considered as a potential prognostic biomarker for LUAD.

Clinical and molecular characteristics of Jordanian oropharyngeal cancer patients according to P16 expression: a retrospective study and a report of a novel biomarker.

The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens andstained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.

Treatment Outcomes of Stereotactic Ablative Body Radiotherapy on Extra-cranial Oligometastatic and Oligoprogressive Breast Cancer: Mature Results from a Single Institution Experience

AimsEvidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. Materials and methodsA retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients’ age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. Results56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0–132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3–28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5–158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. ConclusionThere are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities.

The impact of hypoalbuminemia and its correlation with D-dimer and IL-6 on severity and 14-day mortality in COVID-19 patients

Background &amp; Objective: COVID-19 took the world by storm, but it also allowed the healthcare professionals to conduct big studies regarding various molecular and biochemical changes produced by the disease. We analyzed the impact of hypoalbuminemia on the severity and 14-day mortality in COVID-19 patients.&#x0D; Methodology: It was an analytical observational, prospective cohort study design. Clinical and laboratory data collection was carried out in the COVID-19 isolation room of Dr. Soetomo Hospital, between July and October 2020. Serum albumin, D-dimer, and interleukin 6 (IL-6) levels were measured on the day of admission. Statistical analysis using Kolmogorov-Smirnov, Mann-Whitney test, regression test, ROC curve, and 14-day risk of mortality were tested using Univariate Cox Regression and Multivariate Cox Regression tests. The Kaplan Meier test was used to analyze life expectancy.&#x0D; Results: Of the 119 study subjects, 71 (59.7%) were categorized as severe, and 48 (40.3%) as not severe. Out of the total, 36 (30.25%) patients expired within 14 days of admission, and 83 (69.75%) survived. Regression analysis showed the effect of age on albumin (P &lt; 0.001), albumin on D-dimer (P = 0.003), albumin on disease severity (P &lt; 0.001), and albumin on 14-day mortality (P &lt; 0.001). Albumin was not significantly associated with IL-6 (P = 0.126). The value of albumin as a predictor of severity was 3.28 g/dL, with a sensitivity of 74.6% and a specificity of 77.1%.&#x0D; Conclusion: The state of hypoalbuminemia affects the disease severity and mortality of COVID-19; albumin is significantly associated with D-dimer. Poor prognosis is expected if the albumin value &lt; 3.28 in geriatric and obese patients with a high 14-days mortality.&#x0D; Key words: Albumin; COVID-19; D-dimer; Hypoalbuminemia; IL-6; Severity; Mortality.&#x0D; Citation: Utariani A, Hamzah H, Semedi BP, Sura Wijaya MG. The impact of hypoalbuminemia and its correlation with D-dimer and IL-6 on severity and 14-day mortality in COVID-19 patients. Anaesth. pain intensive care 2023;27(5):440−450; DOI: 10.35975/apic.v27i5.1795&#x0D; Received: February 12, 2022; Reviewed: May 23, 23; Accepted: July 08, 2023

Association of Interferon Lambda 3 and 4 Gene SNPs and Their Expression with COVID-19 Disease Severity: A Cross-Sectional Study.

Expression and certain SNPs of interferon lambda 3 and 4 (IFNL3 and 4) have been associated with variable outcomes in COVID-19 patients in different regions, suggesting population-specific differences in the disease outcome. This study examined the association of INFL3 and INFL4 SNPs (rs12979860 and rs368234815, respectively) and nasopharyngeal expression with COVID-19 disease severity in Pakistani patients. For this study, 117 retrospectively collected nasopharyngeal swab samples were used from individuals with mild and severe COVID-19 disease. qPCR assays were used to determine the viral loads and mRNA expression of IFNL3 and 4 through the Ct and delta Ct methods, respectively. Due to funding limitations, only one SNP each in INFL3 and INFL4 (found to be most significant through literature search) was analyzed using tetra-arm PCR and RFLP-PCR strategies, respectively. The Mann-Whitney U-test was applied to evaluate the statistical differences in the expression of IFNL3/4 genes in the mild and severe groups, while for SNPs, a Chi-square test was employed. A multivariate Cox regression test was performed to assess the relationship of different variables with COVID-19 severity. Comparative analysis of SNPs between mild and severe groups showed only the difference in SNP of the IFNL4 gene to be statistically significant (p = 0.001). Similarly, nasopharyngeal expression of IFNL3 and IFNL4 genes, respectively, was found to be 3.48-fold less and 3.48-fold higher in the severe group as compared to the mild group. Multivariate analysis revealed SNP in the IFNL4 gene and age to have a significant association with COVID-19 severity. Despite the small sample size, IFNL4 gene SNP and patient age were associated with COVID-19 severity. Age, IFNL3/IFNL4 mRNA expression in the nasopharyngeal milieu, and the presence of SNP in the IFNL4 (rs368234815) gene in COVID-19 patients may be biomarkers for infection severity and help improve SARS-CoV-2 infection management.

Effect of HER2 expression status on the prognosis of patients with HR+/HER2‑ advanced breast cancer undergoing advanced first‑line endocrine therapy.

The present study aimed to retrospectively assess the effects of human epidermal growth factor receptor 2 (HER2) expression on the diagnosis of patients with hormone receptor (HR)+/HER2- late-stage breast cancer undergoing advanced first-line endocrine-based treatment. A total of 72 late-stage breast tumor cases from June 2017 to June 2019 were selected from the Department of Surgical Oncology, Shaanxi Provincial People's Hospital (Xi'an, China) and included in the present study. The expression of estrogen receptor, progesterone receptor and HER2 was detected by immunohistochemistry. The subjects were divided into two groups: the HER2-negative (0) cohort (n=31) and the HER2 low expression cohort (n=41). The age, BMI, Karnofsky Performance Status (KPS) score, tumor size, lymph node metastasis, pathological type, Ki-67 expression and menopausal status of the patients were obtained through the electronic medical record system of Shaanxi Provincial People's Hospital. Progression-free survival (PFS) and overall survival (OS) were evaluated for all patients. The median PFS and OS of the HER2(0) cohort were longer than those of the HER2 low expression cohort (all P<0.05). It was shown that age (hazard ratio, 6.000 and 5.465), KPS score (hazard ratio, 4.000 and 3.865), lymph node metastasis (hazard ratio, 3.143; 2.983) and HER2 status (hazard ratio, 3.167 and 2.996) were independent influencing factors of the prognosis of patients with HR+/HER2- advanced breast cancer (ABC) (all P<0.05). Three models (model 1, no parameters adjusted; model 2, BMI, tumor size, pathological type, Ki-67 and menopausal status adjusted; and model 3, age, KPS functional status score and lymph node metastasis adjusted based on model 2) were established within the HER2(0) cohort as the reference for statistical analysis using the multivariate Cox's regression test. In models 2 and 3, the risk of poor prognosis of ABC within the HER2 low expression cohort was significantly higher compared with that in the HER2(0) cohort (hazard ratio, 3.558 and 4.477; 95% CI, 1.349-9.996 and 1.933-11.586; P=0.003 and P<0.001). The HER2 expression status of patients with HR+/HER2- ABC receiving advanced first-line endocrine therapy may affect PFS and OS.

Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database.

Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.

Expression, clinicopathologic, and prognostic significance of MMP15 in operable pancreatic ductal adenocarcinoma

Objective: Matrix metalloproteinase 15 (MMP15) has been previously reported to be involved in many cancers. However, its expression pattern in pancreatic ductal adenocarcinoma (PDAC) remains contradictory. In addition, its clinicopathologic and prognostic significance in this malignancy has not been elucidated. Methods: Expression of MMP15 was immunohistochemically detected in a tissue microarray of formalin-fixed paraffin-embedded samples from 95 patients of PDAC after surgery. Its expression pattern and relations with clinicopathologic factors and disease-specific survival (DSS) were then evaluated. Finally, its expression and prognostic value were measured in the on-line publically available database, GEPIA, using TCGA data. Results: In comparison of all samples and 75 paired ones, MMP15 expression in tumor tissues was all significantly higher than that in para-tumor ones (P = .037 and .016). Furthermore, tumoral MMP15 expression was associated with peri-neural invasion. Survival analysis showed that patients with high tumoral MMP15 expression had significantly poorer DSS than those with low MMP15 expression (P = .0059). In univariate and multivariate Cox regression tests, tumoral MMP15 expression was all significantly predictive for DSS. In the on-line publically available GEPIA database, MMP15 was also overexpressed in PDAC, but was not found to be prognostic. Conclusion: Our results indicated that MMP15 expression was elevated in operable PDAC and might have a prognostic impact.

Predictive worth of estimated glucose disposal rate: evaluation in patients with non-ST-segment elevation acute coronary syndrome and non-diabetic patients after percutaneous coronary intervention

BackgroundMeasurement of estimated glucose disposal rate (eGDR) has been demonstrated to be an indicator of insulin resistance (IR) and a risk sign for long-term outcomes in those with ischemic heart disease and type 2 diabetes mellitus (T2DM) having coronary artery bypass grafting (CABG). After elective percutaneous coronary intervention (PCI), the usefulness of eGDR for prognosis in those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and non-diabetes is yet unknown.Methods1510 NSTE-ACS patients with non-diabetes who underwent elective PCI in 2015 (Beijing Anzhen Hospital) were included in this study. Major adverse cardio-cerebral events (MACCEs), such as all-cause mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and also ischemia-driven revascularization, were the main outcome of follow-up. The average number of follow-up months was 41.84.ResultsAfter multivariate Cox regression tests with confounder adjustment, the occurrence of MACCE in the lower eGDR cluster was considerably higher than in the higher eGDR cluster, demonstrating that eGDR is an independent prognostic indicator of MACCEs. In particular, as continuous variate: hazard ratio (HR) of 1.337, 95% confidence interval (CI) of 1.201–1.488, P < 0.001. eGDR improves the predictive power of usual cardiovascular risk factors for the primary endpoint. Specifically, the results for the area under the receiver operating characteristic (ROC) curve, this is AUC, were: baseline model + eGDR 0.699 vs. baseline model 0.588; P for contrast < 0.001; continuous net reclassification improvement (continuous-NRI) = 0.089, P < 0.001; and integrated discrimination improvement (IDI) = 0.017, P < 0.001.ConclusionLow eGDR levels showed a strong correlation with poor NSTE-ACS prognosis for nondiabetic patients undergoing PCI.

Periprocedural factors associated with overall patient survival following percutaneous image-guided liver tumor cryoablation

Purpose To assess the impact of periprocedural factors, including adverse events, on overall patient survival following image-guided liver tumor cryoablation procedures. Methods In this retrospective single-institution study, 143 patients (73 male, 70 female, ages 29–88) underwent 169 image-guided liver tumor cryoablation procedures between October 1998 and August 2014. Patient, tumor and procedural variables were recorded. The primary outcome was overall survival post-procedure (Kaplan–Meier analysis). Secondary outcomes were the impact of 15 variables on patient survival, which were assessed with multivariate cox regression and log-rank tests. Results Mean tumor diameter was 2.5 ± 1.2 cm. 26 of 143 (18.2%) patients had primary hepatic malignancies; 117 of 143 (81.8%) had liver metastases. Survival analysis revealed survivor functions at 3, 5, 7, 10 and 12 years post-ablation of 0.54, 0.37, 0.30, 0.17 and 0.06, with mean survival time of 40.8 ± 4.9 months. Tumor size ≥4 cm (p = .018), pre-procedural platelet count <100 × 103/μL (p = .023), and prior local radiation therapy (p = .014) were associated with worse overall patient survival. Grade 3 or higher adverse events were not associated with reduced survival (p = .49). Conclusions All variables associated with overall survival were patient-related and none were associated with the cryoablation procedure. Pre-procedural thrombocytopenia, larger tumor size and history of prior local radiation therapy were independent risk factors for reduced overall survival in patients undergoing hepatic cryoablation. Adverse events related to hepatic cryoablation were not associated with decreased survival.

Impact of diabetes mellitus on COVID-19 clinical symptoms and mortality: Jakarta’s COVID-19 epidemiological registry

Background and aimsWhile the higher prevalence of diabetes mellitus (DM) at younger age in Indonesia might contribute to the relatively higher COVID-19 mortality rate in Indonesia, there were currently no available evidence nor specific policy in terms of COVID-19 prevention and management among DM patients. We aimed to find out the association between diagnosed diabetes mellitus (DM) with COVID-19 mortality in Indonesia. MethodsWe performed a retrospective cohort study using Jakarta Province’s COVID-19 epidemiological registry within the first 6 months of the pandemic. All COVID-19 confirmed patients, aged >15 years with known DM status were included. Patients were assessed for their clinical symptoms and mortality outcome based on their DM status. A multivariate Cox-regression test was performed to obtain the relative risk (RR) of COVID-19 mortality in the diagnosed DM group. ResultsOf 20,481 patients with COVID-19, 705 (3.4%) had DM. COVID-19 mortality rate in DM group was 21.28%, significantly higher compared to 2.77% mortality in the non-DM group [adjusted RR 1.98 (CI 95% 1.57–2.51), p < 0.001]. In addition, COVID-19 patients with DM generally developed more symptoms. ConclusionsDM is associated not only with development of more COVID-19 clinical symptoms, but also with a higher risk of COVID-19 mortality. This finding may provide a basis for future policy regarding COVID-19 prevention and management among diabetes patients in Indonesia.

Expression and Prognostic Value of Small Mothers Against Decapentaplegic 7, Matrix Metalloproteinase 2, and Matrix Metalloproteinase 9 in Resectable Pancreatic Ductal Adenocarcinoma.

Thus far, expression, clinicopathologic, and prognostic implication of small mothers against decapentaplegic 7 (Smad7), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in pancreatic ductal adenocarcinoma (PDAC) were rarely investigated or controversial. Expression of Smad7, MMP2, and MMP9 was detected using immunohistochemistry in tissue microarrays based on 322 patients with curatively resected PDAC. Their expression pattern, clinicopathologic, and prognostic relevance were further evaluated. Smad7 expression was found to be lower in tumor than in adjacent nontumor tissues, whereas tumoral MMP2 and MMP9 staining scores were much higher than in adjacent nontumor ones. Furthermore, Smad7 was negatively associated with serum carbohydrate antigen 19-9 level. Univariate survival analyses showed that patients with high Smad7 tumors had significantly better disease-specific survival (P = 0.0007), whereas MMP2 and MMP9 predicted poor disease-specific survival (P = 0.0211 and 0.0404). In multivariate Cox regression test, Smad7 was an independent prognostic indicator (P = 0.021). In addition, these 3 proteins were also prognostic in many subgroups. Smad7 and MMP2/9 significantly predict good or poor prognosis in resectable PDAC, respectively. Therefore, the genes might serve as a tool or targets for molecular therapy in PDAC.

Survival Rate of Colorectal Cancer and Its Effective Factors in Iran

Colorectal cancer is one of the most common cancers in Iran. Regarding the prevalence of this cancer and its mortality and morbidity, in this study, 5 Year Survival Rate and its Effective Factors of patients with colorectal cancer were investigated. This study was conducted using the retrospective cohort method. All patients diagnosed with colorectal cancer in Hamadan Imam Khomeini Clinic of Hematology and Oncology and Mahdieh Oncology Center between 2006 and 2011 were studied. Data were extracted from the patients’ medical records, and to obtain extra information about them, telephone calls were made. The data were analyzed by SPPS version 16, and the assessment of survival rates was conducted using Kaplan-Meier methods and Cox regression method. A total number of 108 patients with colorectal cancer were studied. The status of 74 patients was determined at the end of the study by making follow-up phone calls. The one, two, three, four, and five survival rates were 77, 66, 50, 45, and 42%, respectively. The median overall survival was 46.8 months (1.3-135.6 months). Cox regression analysis showed that Metastatic tumor (P=0.001), lymphatic involvement (P=0.043), and is associated with underlying disease (P=0.025) was accompanied by increased risk. Multivariate cox regression test showed that metastasis was associated with an increase in the risk of death significantly (HR=2.83, P=0.013). According to the findings of the study, early screening is recommended for people with greater risk to increase the survival rate.

An Autophagy-related Long Non-coding RNA Signature for Breast Cancer.

The most prevalent malignant tumor in women is breast cancer (BC). As autophagic therapies have been identified to contribute to BC cell death, the potential prognostic role of long non-coding RNA (lncRNA) related to autophagy in patients with BC was examined. The lncRNAs expression profiles were derived from The Cancer Genome Atlas (TCGA) database. Throughout univariate Cox regression and multivariate Cox regression test, lncRNA with BC prognosis have been differentially presented. We then defined the optimal cut-off point between high and low-risk groups. The receiver operating characteristic (ROC) curves were drawn to test this signature. In order to examine possible signaling mechanisms linked to these lncRNAs, the Gene Set Enrichment Analysis (GSEA) has been carried out. Based on the lncRNA expression profiles for BC, a 9 lncRNA signature associated with autophagy was developed. The optimal cut-off value for high-risk and low-risk groups was used. The high-risk group had less survival time than the low-risk group. The result of this lncRNA signature was highly sensitive and precise. GSEA study found that the gene sets have been greatly enriched in many cancer pathways. Our signature of 9 lncRNAs related to autophagy has prognostic value for BC, and these lncRNAs related to autophagy may play an important role in BC biology.

Expression, clinicopathologic and prognostic significance of plasminogen activator inhibitor 1 in hepatocellular carcinoma.

Thus far, biological roles of plasminogen activator inhibitor 1 (PAI1) in hepatocellular carcinoma (HCC) remain controversial. Moreover, its expression, clinicopathologic and prognostic significance in HCC have not been comprehensively investigated, therefore needing further evidence. PAI1 expression was measured, using tissue microarray-based immunohistochemical staining, in matched HCC and adjacent liver samples from 178 patients with HCC after curative resection. The correlations of PAI1 H-scores with clinicopathologic variables and survival were further evaluated. Its prognostic value was finally confirmed in some public databases. It was found that PAI1 expression was significantly higher in HCC than in adjacent liver tissues. Moreover, high PAI1 expression was more frequent in those with multiple lesions. Univariate analyses showed that PAI1 expression was negatively associated with both overall and relapse-free survival. Although PAI1 expression was not statistically significant in multivariate Cox regression test, combination of it with TNM stage effectively distinguished survival and relapse, and served as an independent prognostic factor. In the online available datasets of HCC and liver cancer used, SERPINE1, the gene encoding PAI1, was also revealed to be prognostic. Our data suggested that high PAI1 expression was predictive for unfavorable biological behavior and long-term prognosis in HCC.

High MMP14 expression is predictive of poor prognosis in resectable hepatocellular carcinoma

Matrix metalloproteinase 14 (MMP14) has been found to play multiple biological roles in cancers, including hepatocellular carcinoma (HCC). Up to now, its expression, clinicopathological and prognostic implications in HCC have not been comprehensively investigated. In the present study, MMP14 expression was detected, using tissue microarray-based immunohistochemical staining, in paired HCC and adjacent liver (AL) samples from 260 patients who underwent radical hepatectomy. The associations of MMP14 staining H-scores with clinicopathological parameters, overall and disease-free survival were then evaluated. Finally, its expression and prognostic value were confirmed in some online publicly available databases. It was shown that MMP14 expression was significantly higher in HCC than in AL tissues (p=0.035). Furthermore, MMP14 expression correlated positively with tumour size, Edmondson-Steiner grade and α-fetoprotein level (p<0.05). For survival, MMP14 expression was negatively associated with both overall and disease-free survival in univariate analyses (p<0.05), while it remained statistically significant for disease-free survival by multivariate Cox regression test. In the Ualcan and Kaplan-Meier Plotter databases, MMP14 was also revealed to be overexpressed and prognostic. Taken together, our study indicated that high MMP14 expression was predictive for unfavourable biological behaviours and long-term prognosis in resectable HCC.

Survival Rates of Endodontically Treated Teeth After Placement of Definitive Coronal Restoration: 8-Year Retrospective Study.

IntroductionPreservation of endodontically treated teeth (ETT) depends upon several patient-related and operator-related factors. The objectives of this study were to assess the effects of different types of coronal restoration and delayed placement on ETT survival.MethodsData on dates of root canal treatment (RCT), restoration type, and extraction time of tooth, when applicable, were analyzed for all patients who underwent RCT from 2010 to 2018 at our institution.Inclusion CriteriaRoot canal-treated teeth with complete preoperative and postoperative radiographs; ETT that were restorable and received final permanent coronal restorations; no periodontal disease or crack detected during RCT; and ETT with acceptable RCT quality.Exclusion CriteriaPatients who did not attend for follow-up, those had incomplete information available about the coronal restoration, and those with periodontally compromised teeth were excluded. ETT that involved any procedural error were also excluded. The teeth were categorized according to whether they underwent definitive coronal restoration 0–14 days, 15–59 days, or 60+ days after RCT. The statistical analysis was performed using SPSS version 25 (IBM Corp., Armonk, NY). The rate of survival of ETT of 8 years was estimated, and the differences between groups were determined after applying Kaplan–Meier statistics and log-rank tests. A multivariate Cox regression test and Wilcoxon (Gehan) statistics were computed to analyze the influence of different variables. A P-value <0.05 was considered as statistically significant.ResultsThe type of restoration, opposing dentition, presence of a post, and dentistry training (year 4 or 5 students) showed significant effects on the survival of ETT (P ≤ 0.000). ETT which received crowns was 2.05 times more likely to need extraction than those in which a composite buildup was performed (hazard ratio [HR] 2.05; confidence interval [CI] 1.84–2.29; P ≤ 0.000). All composite buildups were performed within 14 days of completion of RCT. There was a significant correlation between the time of placement of the final coronal restoration and ETT survival (P ≤ 0.000). Extraction of ETT was 25% more likely (HR 0.25; CI 0.231–0.277) when the final coronal restoration was placed 15–59 days after completion of RCT and 73% more likely (HR 0.73; CI 0.655–0.814) when placed after 60 days than when placed at 0–14 days.ConclusionTimely placement of the final coronal restoration is found to be the most critical factor affecting the long-term survival of teeth after RCT.

Expression and prognostic significance of melatonin receptor MT1 in patients with gastric adenocarcinoma.

Melatonin receptor type 1 (MTNR1A or MT1) is known to play an important role in cancer progression; however, its prognostic value for resected gastric adenocarcinoma (RGA) is unknown. In this study, we examined the potential of MT1 as a prognostic biomarker for RGA. The expression of the MT1 was evaluated in 67 patients with RGA by immunohistochemistry, and the relationship between MT1 levels and RGA prognosis was analyzed by Chi-square test, multivariate Cox regression, Kaplan-Meier method, and log-rank test. High MT1 expression was associated with a poor survival rate (29.0%, p=0.002) and the occurrence of metastasis (62.9%, p=0.004). Kaplan-Meier survival analysis and log rank tests revealed that patients with high expression of the MT1 had significantly shorter median overall survival compared to those with low expression (33.0 vs. 65.0 months, respectively; p=0.02). Multivariate Cox analysis indicated that the calculated death risk (hazard ratio [HR]) in patients with high expression levels of the MT1 increased to 2.68 (95% confidence interval [CI] 1.21-5.94, p=0.015), which was higher compared to those with low levels. HR of death was also high in patients with advanced T stage (2.51; 95 % CI 1.00-6.26, p=0.049) and metastasis (5.02; 95% CI 1.94-13.03, p=0.001). Our results showed that high MT1 expression in primary gastric adenocarcinoma tissues was associated with the occurrence of metastasis and poor prognosis. It may have prognostic significance as a potential biomarker in patients with RGA.

The role of surgery and radiation in advanced gastric cancer: A population-based study of Surveillance, Epidemiology, and End Results database.

BackgroundChemotherapy is the standard approach for advanced gastric cancer, while the role of local therapy such as surgery and radiation for this population remains controversial. Our purpose is to evaluate the effect of local therapies on cancer specific survival (CSS) for advanced gastric cancer patients.MethodsFour subgroups of patients in different treatment strategies: surgery, radiation (RT), surgery and radiation (Surgery+RT), no surgery/no radiation (No Surgery/No RT) were identified from the Surveillance, Epidemiology, and End Results (SEER)-registered database. The risk factors and the survival outcomes were analyzed by multivariable Cox regression models and Kaplan-Meier methods.ResultsA total of 10,354 patients were eligible with 6658 males and 3696 females. The 5-year CSS in the four subgroups of “Surgery”, “RT”, “Surgery+RT” and “No Surgery/No RT” were respectively 8.9%. 5.7%, 19.8% and 3.2%, which were significantly different in multivariate Cox regression (P<0.001) and univariate log-rank test (P<0.001). Advanced stage categories were defined as stage I, II and III of T/N category according to different initial T and N status following American Joint Committee on Cancer (AJCC) staging principle. Further analysis showed that patients in the group of “Surgery+RT” have significant benefits of survival specifically on stage II and III of T/N category. “Surgery+RT” group and “Surgery” group patients have similar survival time in stage I of T/N category. Moreover, we also found CSS benefits from the administration of “Surgery+RT” in the patients aged both ≥75 and <75 years. Remarkably, patients in “Surgery” group have no different survival time with “RT” group in age category of 75 years and older.ConclusionsLocal therapies, including surgery, radiation, and combination of both might associate to improve survival in advanced gastric cancer patients, but confounding due to disease extent and physical status cannot be excluded.

Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma.

Background:Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue.Methods:PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses.Results:Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = −2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = −2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ2 = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499–4.367, P = 0.001).Conclusion:These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.