Clinicopathological Variables Of Patients Research Articles

Expression of β1- and β2-adrenergic receptors in oral squamous cell carcinoma and their association with psychological and clinical factors

BackgroundPsychological stressors have been related to tumor progression through the activation of beta-adrenergic receptors (β-AR) in several types of cancer. Purpose: This study aimed to investigate the expressions of β1- and β2-AR and their association with psychological and clinicopathological variables in patients with oral squamous cell carcinoma. Methods: Tumor samples from 99 patients diagnosed with OSCC were subjected to immunohistochemical reaction to detect the expression of β1-AR and β2-AR. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory and Beck Depression Inventory (BDI), respectively. The Brunel Mood Scale was used for measuring affective mood states. Results: Univariate analyzes revealed that higher expression of β1-AR was associated with increased alcohol consumption (p = 0.032), higher education (p = 0.042), worse sleep quality (p = 0.044) and increased levels of pain related to the primary tumor (p < 0.001). Higher expression of β2-AR was related with regional metastasis (p = 0.014), increased levels of pain related to the primary tumor (p = 0.044), anxiety (p < 0.001) and depressive (p = 0.010) symptoms and higher mood scores of angry (p = 0.010) and fatigue (p = 0.010). Multivariate analysis identified that patients with advanced clinical stage had lower β1-AR expression (OR=0.145, 95% CI=0.025–0.828, p = 0.003). Higher anxiety symptoms and higher mood fatigue are independent factors for increased β2-AR expression (OR=4256, 95% CI=1439–12606, p = 0.009; OR=3816, 95% CI=1258–11,573, p = 0.018, respectively). Conclusion: This study reveal that anxiety, fatigue symptoms, and clinical staging are associated with tumor expression of beta-adrenergic receptors in patients with oral cancer.

Single-port robotic extraperitoneal pediatric pyeloplasty using low anterior access: Description of technique and initial experience

IntroductionWe aim to report our surgical technique, functional and radiological outcomes of single port (SP) extraperitoneal robotic pediatric pyeloplasty through a low anterior (3cm) access using a da-Vinci single-port (SP) robotic surgical system in the pediatric population. Material and methodsWe present our initial series of 6 pediatric patients that underwent robotic SP extraperitoneal pyeloplasty between 2022 - 2023. Patient clinicopathologic variables and perioperative outcomes were collected prospectively. ResultsAll cases of SP extraperitoneal pyeloplasty were completed without any intraoperative complications or conversion to an open, laparoscopic, or multi-port robotic pyeloplasty. Total operative times including cystoscopy ranged from 178 mins to 240 mins. All patients tolerated the surgery with minimal postsurgical pain and no narcotic requirement. No intraoperative or immediate postoperative complications were recorded in the cohort. There were no readmissions after discharge at a median follow-up of 12 months (6-18 months) in our series. ConclusionsSingle port extraperitoneal pyeloplasty is a safe and feasible option for upper tract reconstruction in pediatric patients. All patients had complete resolution of symptoms and improvement of hydronephrosis on follow-up imaging.

Evaluation of Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 (HER2) and its Association with Clinicopathological Variables in Patients with Pancreatic Duct Adenocarcinoma in Upper Egypt

Evaluation of Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 (HER2) and its Association with Clinicopathological Variables in Patients with Pancreatic Duct Adenocarcinoma in Upper Egypt

Development and validation of nomograms for predicting the risk of central lymph node metastasis of solitary papillary thyroid carcinoma of the isthmus

BackgroundThis study was conducted to develop nomograms and validate them by assessing risk factors for the development of central lymph node metastasis (CLNM) in patients with solitary papillary thyroid carcinoma of the isthmus (PTCI) for predicting the probability of CLNM.MethodsDemographic and clinicopathological variables of patients with solitary papillary thyroid carcinoma (PTC) from May 2018 to May 2023 at the First Hospital of Shanxi Medical University were retrospectively analyzed, and the lobar group and the isthmus group were divided according to tumor location. Patients with the same sex, age difference of less than 3 years, and equal gross tumor diameter were selected from the lobar group and compared with the paraisthmic tumor group. Independent risk factors were determined using univariate and multivariate logistic regression analysis. On this basis, clinical predictive nomograms were developed and validated.ResultsClinical data from 326 patients with solitary PTCI and 660 cases of solitary lobar PTC were used for analysis in our study. The incidence of solitary tumors CLNM located in the median isthmus, paracentral isthmus, and lobes was 69.8%, 40.9%, and 33.6%, respectively. Statistical analysis revealed that gender, age, isthmus location, maximum nodal diameter, the presence of possible CLNM in advance on preoperative ultrasound, chronic lymphocytic thyroiditis, and the lymphocyte/monocyte ratio were independent risk factors for preoperative CLNM in patients with solitary PTCI. Age, isthmus location, chronic lymphocytic thyroiditis, gross tumor diameter, presence of intraoperative extrathyroidal extension, and presence of metastasis in the Delphian lymph node on frozen section were independent risk factors for intraoperative CLNM. The concordance indices of nomograms for preoperative and intraoperative are 0.871 and 0.894 in the training set and 0.796 and 0.851 in the validation set, calibration curve and decision curve analysis also demonstrated the strong reliability and clinical applicability of this clinical prediction model.ConclusionIn this study, we concluded that solitary PTCI is more aggressive compared to solitary lobar PTC, and we constructed nomograms and risk stratification to accurately identify patients with solitary PTCI who are at high risk of developing CLNM, which will help clinicians in personalized decision making.

Development and validation of a nomogram for risk of pulmonary metastasis in non-papillary thyroid carcinoma: A SEER-based study.

In this study, a nomogram was established and validated by assessing the risk factors for the development of pulmonary metastases in patients with non-papillary thyroid carcinoma (NPTC) and was used to predict the risk of developing pulmonary metastases. Demographic and clinicopathological variables of patients with NPTC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed, and independent risk factors were identified using χ2 tests and full subset regression analysis. Based on this, a nomogram was developed and validated for predicting the risk of pulmonary metastasis in patients with NPTC. The predictive performance of the nomogram was calculated using the consistency index, and the clinical application value of the nomogram was evaluated using calibration curve and decision curve analyses. In addition, risk stratification of patients with NPTC based on these results was performed to facilitate early diagnosis and treatment of patients with pulmonary metastases in the clinic. Data from 1435 patients with NPTC were used for the analysis based on the inclusion and exclusion criteria. Statistical analysis yielded a high risk of pulmonary metastasis in patients with older age, high T-stage, poorly differentiated, undifferentiated thyroid carcinoma, follicular thyroid carcinoma (NOS), and the presence of other distant metastases. We further developed a nomogram with a consistency index of 0.898 (95% confidence interval: 0.880-0.920) in the training cohort and 0.895 (95% confidence interval: 0.862-0.927) in the validation cohort. The calibration curve and decision curve analyses also demonstrated the strong reliability and accuracy of this clinical prediction model. In this study, a nomogram was constructed to accurately identify patients with NPTC at a high risk of pulmonary metastasis, which will help clinicians in personalized decision-making.

Development and External Validation of Machine Learning-Based Models for Predicting Lung Metastasis in Kidney Cancer: A Large Population-Based Study.

The accuracy of indices widely used to evaluate lung metastasis (LM) in patients with kidney cancer (KC) is insufficient. Therefore, we aimed at developing a model to estimate the risk of developing LM in KC based on a large population size and machine learning algorithms. Demographic and clinicopathologic variables of patients with KC diagnosed between 2004 and 2017 were retrospectively analyzed. We performed a univariate logistic regression analysis to identify risk factors for LM in patients with KC. Six machine learning (ML) classifiers were established and tuned using the ten-fold cross-validation method. External validation was performed using clinicopathologic information from 492 patients from the Southwest Hospital, Chongqing, China. Algorithm performance was estimated by analyzing the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, recall, F1 score, clinical decision analysis (DCA), and clinical utility curve (CUC). A total of 52,714 eligible patients diagnosed with KC were enrolled, of whom 2,618 developed LM. Variables of age, sex, race, T stage, N stage, tumor size, histology, and grade were identified as important for the prediction of LM. The extreme gradient boosting (XGB) algorithm performed better than other models in both the internal validation (AUC: 0.913, sensitivity: 0.873, specificity: 0.809, and F1 score: 0.325) and the external validation (AUC: 0.904, sensitivity: 0.750, specificity: 0.878, and F1 score: 0.364). This study established a predictive model for LM in KC patients based on ML algorithms which showed high accuracy and applicative value. A web-based predictor was built using the XGB model to help clinicians make more rational and personalized decisions.

V03-01 SINGLE-PORT KIDNEY AUTO-TRANSPLANTATION (SP-KAT) WITH BOARI FLAP URETERAL REIMPLANT: DESCRIPTION OF OUR NOVEL APPROACH

You have accessJournal of UrologyCME1 Apr 2023V03-01 SINGLE-PORT KIDNEY AUTO-TRANSPLANTATION (SP-KAT) WITH BOARI FLAP URETERAL REIMPLANT: DESCRIPTION OF OUR NOVEL APPROACH Jaya Sai Chavali, Jihad Kaouk, Ethan Ferguson, Roxana Ramos, Albert Geskin, Alvin Wee, and Mohamed Eltemamy Jaya Sai ChavaliJaya Sai Chavali More articles by this author , Jihad KaoukJihad Kaouk More articles by this author , Ethan FergusonEthan Ferguson More articles by this author , Roxana RamosRoxana Ramos More articles by this author , Albert GeskinAlbert Geskin More articles by this author , Alvin WeeAlvin Wee More articles by this author , and Mohamed EltemamyMohamed Eltemamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003241.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aim to demonstrate the feasibility and safety of the novel minimally invasive technique for efficient, multiquadrant robotic kidney transplantation using da Vinci single-port robot platform (SP-KAT). The study patient had a good split renal function and complete ureter avulsion. METHODS: Eight consecutive patients underwent SP KAT using the DaVinci SP platform. Overall patient clinicopathologic variables were recorded in Table 1. We demonstrate our technique in 58 year old male that presented after complete avulsion of the ureter during ureteroscopy. He had good split renal function on imaging. Technical steps of the surgery included (1). Robotic nephrectomy; (2) Kidney benching; (3) Dissection of Iliac vessels and Kidney placement; (4) Vascular anastomosis; (5) Ureteral reimplant. Extra corporeal kidney benching performed at the same time while the iliac vessels are being exposed robotically for subsequent transplant. This patient in addition required Boari flap ureteroneocystostomy due to insufficient length of ureter. RESULTS: All SP KAT cases were successfully performed without repositioning or conversion to open. Total operative time was 701 minutes. Estimated blood loss was 500cc. The Foley and stent removed at 2 and 6 weeks postoperatively. Patient had complete preservation of renal function. No documented postoperative complications up to latest follow up at 1 year. CONCLUSIONS: We demonstrate our single-port efficient, multiquadrant robotic kidney transplantation technique performed though a single incision further reducing surgical morbidity. All the cases were completed successfully without conversion or loss of graft function. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e246 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jaya Sai Chavali More articles by this author Jihad Kaouk More articles by this author Ethan Ferguson More articles by this author Roxana Ramos More articles by this author Albert Geskin More articles by this author Alvin Wee More articles by this author Mohamed Eltemamy More articles by this author Expand All Advertisement PDF downloadLoading ...

MP31-01 SINGLE-PORT ROBOTIC KIDNEY AUTOTRANSPLANTATION (SP-KAT) - EARLY LEARNING CURVE

You have accessJournal of UrologyCME1 Apr 2023MP31-01 SINGLE-PORT ROBOTIC KIDNEY AUTOTRANSPLANTATION (SP-KAT) - EARLY LEARNING CURVE Jaya Sai Chavali, Ethan Ferguson, Sanjay Vallabhaneni, Albert Geskin, Zeyad Schwen, Roxana Ramos, Alp Tuna Beksac, Alvin Wee, Mohamed Eltemamy, and Jihad Kaouk Jaya Sai ChavaliJaya Sai Chavali More articles by this author , Ethan FergusonEthan Ferguson More articles by this author , Sanjay VallabhaneniSanjay Vallabhaneni More articles by this author , Albert GeskinAlbert Geskin More articles by this author , Zeyad SchwenZeyad Schwen More articles by this author , Roxana RamosRoxana Ramos More articles by this author , Alp Tuna BeksacAlp Tuna Beksac More articles by this author , Alvin WeeAlvin Wee More articles by this author , Mohamed EltemamyMohamed Eltemamy More articles by this author , and Jihad KaoukJihad Kaouk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003264.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We present our initial series of single-port (SP) robotic KAT, ideal for multi-quadrant surgeries, and aim to evaluate the feasibility and safety of the novel approach. METHODS: Ten consecutive patients underwent robotic SP KAT and indications include complex or recurrent ureteral stricture, ureteral avulsion, chronic visceral pain due to multiple etiologies and failed prior surgeries. Extra corporeal kidney benching performed at the same time while the iliac vessels are being exposed robotically for subsequent transplant. Overall patient clinicopathologic variables and perioperative outcomes were recorded in Tables 1, 2. RESULTS: All SP KATs were successfully performed without repositioning or conversion to open or loss of graft function. Operative times ranged from 366 to 701 mins with a warm and cold ischemia time between 4 to 10 mins and 86 to 209 mins, respectively. Median hospital length of stay was 4 days. The learning curve in our case series was hard to evaluate given each individual patient presents a unique challenge but overall ischemia and revascularization times showed progressive improvement (Figure 1). There was one Clavien-Dindo 3 complication, an unrecognized bowel injury that required re-operation in our series. At a median of 8 months follow-up, latest postoperative GFRs were stable, ranging from +23% to −14%, and the grafts were functioning well. Notably, all patients who had preoperative chronic visceral pain had complete resolution of pain postoperatively. CONCLUSIONS: We demonstrate our single-port multi quadrant robotic kidney auto transplantation technique performed through a single incision further reducing surgical morbidity. All the cases reported improvement in flank pain and no radiological evidence of urinary obstruction on follow up. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e429 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jaya Sai Chavali More articles by this author Ethan Ferguson More articles by this author Sanjay Vallabhaneni More articles by this author Albert Geskin More articles by this author Zeyad Schwen More articles by this author Roxana Ramos More articles by this author Alp Tuna Beksac More articles by this author Alvin Wee More articles by this author Mohamed Eltemamy More articles by this author Jihad Kaouk More articles by this author Expand All Advertisement PDF downloadLoading ...

Predictive value of inflammatory markers in gastric cancer

Aim: Many recent studies are increasingly shedding light on the nature of the relationship between cancer and inflammation. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) platelet/neutrophil ratio (PNR), and Mean Platelet Volume (MPV) are proinflammatory markers, and their prognostic importance has been investigated in many solid cancers. In this study, we discussed the association of these derivative inflammatory markers, obtained from a cheap and simple peripheral blood test, with clinicopathologic variables in patients undergoing gastrectomy for gastric cancer.&#x0D; Material and Method: The retrospective database of a total of 148 patients who were operated for gastric cancer in the Diyarbakır Gazi Yaşargil Training and Research Hospital Department of Surgery was analyzed. All blood results and pathology reports of the patients were reviewed retrospectively. Demographic characteristics of the patients and pathological features of the tumor were extracted from the database. NLR, PLR, PNR and MPV values were calculated from peripheral blood cell counts. Data were analyzed using SPSS version 24.0.&#x0D; Results: PNR and MPV values were statistically significant according to N and T stage of the tumor, respectively (p=0.035, p=0.011). In MPV, this difference was statistically observed between T1 and T2 tumors (p=0.029). PLR and NLR values did not show a significant difference according to the size of the tumor (p&gt;.05).&#x0D; Conclusion: MPV values are significantly associated with tumor T stage. PNR values are significantly associated with tumor N stage. However, the clinical implications and the added value to clinical practice require further research.

Single Port Robotic Kidney Autotransplantation: Initial Case Series and Description of Technique

PurposeMinimally invasive kidney autotransplantation (KAT) has demonstrated reduced morbidity, however multiport robotic approach required patient repositioning and multiple sets of incisions. We present our initial series of single-port (SP) robotic KAT, ideal for multi-quadrant surgeries, and aim to evaluate feasibility and safety of the novel approach. MethodsBetween 2018 and 2022, 8 consecutive patients underwent SP KAT using the DaVinci SP platform. Patient clinicopathologic variables and perioperative outcomes were recorded. Indications for KAT include complex or recurrent ureteral stricture, ureteral avulsion, and chronic visceral pain due to multiple etiologies. ResultsAll SP KATs were successfully performed without repositioning or conversion to open. Operative times ranged from 366 to 701 minutes, warm and cold ischemia times between 4 to 10 minutes and 86 to 209 minutes, respectively. Median hospital length of stay was 3 days. At a median of 13 months follow-up, latest postoperative GFRs were stable, ranging from +23% to -10%. There were no complications. ConclusionWe demonstrate our single port, multiquadrant robotic kidney auto transplantation technique performed though a single incision further reducing surgical morbidity. All cases were completed successfully without conversion or loss of graft function. All patients reported resolution of flank pain and no radiological evidence of urinary obstruction on follow up.

Clinical utility of IDC-P (intraductal carcinoma of the prostate) in the decision making of initial treatment for metastatic hormone-sensitive prostate cancer.

93 Background: In recent years, the usefulness of using androgen receptor axis-targeted agents (ARAT) such as abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer (mHSPC) in the up-front setting has been demonstrated. However, it is still unclear which patients could truly benefit from these treatments. On the other hand, intraductal carcinoma of prostate (IDC-P) is a known poor prognostic factor for prostate cancer patients. In the present study, we investigated the association between the presence of IDC-P and therapeutic response to mHSPC. Methods: This retrospective analysis included 318 patients with mHSPC from thirteen affiliated institutions between 2014 and 2021, and evaluated biopsy specimens for the presence of IDC-P. All patients were grouped by their first-line treatment, either ARAT (n=100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT), or conventional therapy (n=218, receiving ADT with or without standard antiandrogen agents). We compared overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts response to each treatment. The PFS2 was defined as the period from diagnosis of mHSPC to disease progression on second-line therapy or death. Propensity score matching was used for one-to-one nearest neighbor matching in order to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of patients were well balanced after propensity score matching. Results: Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, OS and PFS2 of IDC-P positive cases were significantly prolonged in the ARAT group compared to the conventional group (OS: hazard ratio [HR], 0.36; p=0.047; PFS2: HR, 0.30; p&lt;0.001). In contrast, IDC-P negative cases did not show a difference in OS and PFS2 between the ARAT and the conventional groups (OS: HR, 1.09; p=0.920; PFS2: HR, 0.40; p=0.264). Conclusions: The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P may be a reliable indicator to implement ARAT as first-line therapy.

Correlation between Ubiquitin E3 Ligases (SIAHs) and Heat Shock Protein 90 in Breast Cancer Patients.

Background:Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR, and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.Methods:The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85 invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018–2019, and its association with the clinicopathologic variables of patients was evaluated.Results:HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor tissue of patients with breast cancer. Moreover, this study observed a significant association between the high expression of SIAH2/HSP90 with ER status, high expression of HSP90 with Recurrence/Metastasis, and high expression of SIAH2 with Ki-67 proliferation index.Conclusion:The HSP90 and SIAH2 expressions play a significant role in breast cancer development by combining the experimental and clinical data obtained from the literature.

Predictive value of CCR3 expression on diagnosis and prognostic classification of the Prostate Adenocarcinoma

Objective: Chemokines are factors secreted from damaged or infected tissues to induce an inflammatory and immunological reaction. Approximately Chemokines have recently been found to be secreted by most cancer cells. The aim of this study is to compare the CCR-3 expression with the clinicopathological variables in patients with prostatic adenocarcinoma(PCa) and benign prostatic hyperplasia(BPH). Material Method: The study included 25 patients with PCa who underwent prostatectomy, 25 patients with BPH. In the study, CCR-3 expression in PCa and BPH tissues was examined by immunohistochemical method, and CCR-3 expression at PCA and BPH tissues was compared with normal prostate tissue at mRNA level by the Real-Time PCR. Results: CCR-3 expression was found to be significantly higher in PCa patients (p=0,001). There was no relationship between Gleason prognostic grade and periprostatic spread and CCR-3 expression (p=0,887, p=0,279). A statistically significant increase was found in total PSA and CCR-3 expression (p=0,001). Conclusion: In prostate cancer, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence. According to this study, the CCR-3 expression may be useful in predicting the diagnosis of PCa and there was a significant relationship between total PSA. The Increasing total PSA was also correlation to increased of the CCR3 expression. However, there was no significant relationship between Gleason prognostic grade.

Correlations of demographical and clinicopathological features with patient outcome of pancreatic ductal adenocarcinoma: A retrospective study (2010-2018) from a Libyan Cohort.

The aim of the study was to study the correlations of demographical and clinicopathological variables of patients with pancreatic ductal adenocarcinoma (PDAC) and evaluate the association of these variables with patients' survival outcomes. A retrospective analysis of 123 patients with PDAC were diagnosed and treated at the National Cancer Institute, Misurata, Libya during the 2010-2108 period. Data for demographics, clinicopathological, biological variables, risk factors, presentation, treatment, and survival-related data were collected from the patients' medical records. The mean age of patient was 61.2 years (range: 19-90 years) and most of patients (80.5%) were aged >50 years. For gender distribution, PDAC was more frequent in males (59.3%). Abdominal pain was the most frequent presenting symptom (84.6%) and 78% (96 patients) among them had head tumors. Most patients (80.5%) presented with unresectable tumor at diagnosis. Disease-free survival was better in patients with early stage (P < 0.0001), low-grade tumor (P = 0.001), resectable tumor (P < 0.0001), and with carcinoembryonic antigen levels <5 ng/ml (P = 0.004). Multivariate Cox's regression analysis showed that tumor stage is an independent poor survival factor (P = 0.002). Age at diagnosis, gender, family history, and position of tumor did not show any significant associations with patient outcome. Libyan patients with PDAC had different demographics, clinicopathological, and biological variables. Typically, they presented with unresectable tumor, advanced stages, and had very short survival times. These results urge us to conduct in-depth biomolecular research studies to identify effective early diagnostics and therapeutics biomarkers in order to fight this disease before it escalates.

RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells via the PI3K/AKT/mTOR Pathway.

BackgroundBladder cancer (BCa) is one of the most frequent malignant tumors globally, with a significant morbidity and mortality rate. Gene expression dysregulation has been proven to play a critical role in tumorigenesis. Ras-related C3 botulinum toxin substrate3 (RAC3), which is overexpressed in several malignancies and promotes tumor progression, has been identified as an oncogene. However, RAC3 has important but not fully understood biological functions in cancer. Our research aims to reveal the new functions and potential mechanisms of RAC3 involved in BCa progression.MethodsWe explored the expression level of RAC3 and its relationship with prognosis by publicly accessible BCa datasets, while the correlation of RAC3 expression with clinicopathological variables of patients was analyzed. In vitro and in vivo proliferation, migration, autophagy, and other phenotypic changes were examined by constructing knockdown(KD)/overexpression(OE) RAC3 cells and their association with PI3K/AKT/mTOR pathway was explored by adding autophagy-related compounds.ResultsCompared with non-tumor samples, RAC3 was highly expressed in BCa and negatively correlated with prognosis. KD/OE RAC3 inhibited/promoted the proliferation and migration of BCa cells. Knockdown RAC3 caused cell cycle arrest and decreased adhesion without affecting apoptosis. Inhibition of RAC3 activates PI3K/AKT/mTOR mediated autophagy and inhibits proliferation and migration of BCa cells in vivo and in vitro. Autophagy inhibitor 3MA can partially rescue the metastasis and proliferation inhibition effect caused by RAC3 inhibition. Inhibit/activate mTOR enhanced/impaired autophagy, resulting in shRAC3-mediated migration defect exacerbated/rescued.ConclusionRAC3 is highly expressed in BCa. It is associated with advanced clinicopathological variables and poor prognosis. Knockdown RAC3 exerts an antitumor effect by enhancing PI3K/AKT/mTOR mediated autophagy. Targeting RAC3 and autophagy simultaneously is a potential therapeutic strategy for inhibiting BCa progression and prolonging survival.

A novel circRNA, circRACGAP1, hampers the progression of systemic lupus erythematosus via miR-22-3p-mediated AKT signalling

Background Systemic lupus erythematosus (SLE) is defined as a multisystem autoimmune disease involving various organs, of which exact molecular mechanisms remain elusive. Here, we aimed to investigate a novel circular RNA (circRNA), circRACGAP1, abnormally expressed in SLE and explored its underlying regulatory network. Methods The expression patterns of circRACGAP1 were determined in patients diagnosed with SLE by using a qRT-PCR assay. Spearman correlation analysis was employed to evaluate the correlation between circRACGAP1 and clinicopathological variables in patients with SLE. Flow cytometry and TUNEL assays were subjected to assess the cell apoptosis. Nuclear-cytoplasmic fractionation and luciferase reporter assay was used to verify the circRACGAP1/miR-22-3p/PTEN axis. Western blot analysis was performed to measure the PTEN/AKT signalling-related proteins and apoptotic-related biomarkers. Results Down-regulated circRACGAP1 was observed and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds) DNA, and complement C3 level in patients with SLE. Overexpression of circRACGAP1 significantly alleviated cell apoptosis in Jurkat cells within UVB exposure. Mechanistic investigation revealed that circRACGAP1 could serve as a sponge of miR-22-3p to regulate PTEN/AKT signalling. Conclusions Collectively, circRACGAP1 regulated the AKT signalling pathway via binding to miR-22-3p in the progression of SLE, suggesting therapeutic targets for SLE treatment.

Abstract P1-04-07: Xiap expression is associated with infiltration of cd163+ tumor-associated macrophages in the tumor micro-environment of inflammatory breast cancer

Abstract BACKGROUND: Inflammatory breast cancer (IBC) is a rare, but aggressive type of locally advanced breast cancer for which a specific immune response seems to be an important driver (Van Laere et al., CCR 2013). The tumor immune micro-environment (TIME) of IBC is characterized by an influx of tumor-associated macrophages (TAMs) and patients with spatial colocalization of TAMs with tumor cells seem to have a worse prognosis (Van Berckelaer et al., SABCS 2019). In contrast with TAMs, the presence of CD8+ T cells was associated with a better prognosis in IBC. Cytotoxic T cells mediate killing of the tumor by inducing apoptosis after activation of effector caspases-3/-7, regulated by the X-Linked Inhibitor of Apoptosis protein (XIAP). Recently, we reported that XIAP in breast cancer is associated with shorter survival and resistance to chemotherapy (Devi et al, Cancers 2021). In IBC, XIAP is translationally upregulated during cellular stress and induces, via NFkB, an immunosuppressive signaling (Evan et al, Cancer Res 2018). Therefore, we investigated the interplay between tumor cell driven XIAP expression and the TIME. METHODOLOGY: IBC patient clinicopathological variables (n=75) along with Affymetrix data (n=30/75) were collected. Immunostainings for XIAP, CD8 and CD163 (Hematoxylin-DAB) were done according to validated protocols. All slides were digitized and evaluated in Visiopharm to quantify the number of DAB+ immune cells and the relative marker area (RMA: the DAB+ area/total area of interest). Spatial interactions were examined using an effector index (EI) that counts the number of immune cells in a circle with a radius of 30 mcm around a CD8+ T cell or a tumor cell. We evaluated correlations between XIAP protein and mRNA expression, immune cell signatures (using CIBERSORT) &amp; gene-expression pathways as a validation of our IHC findings. RESULTS: High XIAP expression was detected in 45.3% of the IBC samples (n= 34/75). Although, XIAP expression was not associated with any clinicopathological parameters like grade, molecular subtype, or disease stage. High XIAP expressing tumors had more sTIL infiltration (P= 0.008), PDL1 expression (P= 0.012) and infiltration with TAMs (RMA: 1.03% (0.03% – 5.97%) vs. 2.73% (0.01% – 11.3%), P= 0.003). Furthermore, in these XIAP high samples TAMs were also located closer to the tumor cells (EI: 0.95 cells (0.06 – 3.48) vs. 2.04 cells (0.28 – 5.20), P&amp;lt; 0.001) and the CD8+ T cells (EI: 2.85 cells (0.26 – 8.85) vs. 5.13 cells (0.87 – 10.16), P&amp;lt; 0.001), while there was no correlation between XIAP and the total number of CD8+ cells. Although gene expression data analysis did not reveal any correlation between protein and mRNA expression of XIAP, there was a significant correlation between XIAP activation signature and protein expression (P&amp;lt;0.001). Furthermore, we discovered a strong association between XIAP protein and cellular stress response- &amp; inflammation-related gene sets. Finally, in the CIBERSORT data, we observed the strongest correlation between XIAP expression and M2 macrophages &amp; activated dendritic cells. CONCLUSION: This is the first study showing high XIAP expressing IBC tumors have increased infiltration of immunosuppressive TAMs, which co-localized near tumor and cytotoxic T cells. We also demonstrated an association between XIAP protein expression and inflammation related &amp; cellular stress response gene signatures. This is relevant as XIAP function depends on translational upregulation during cellular stress which leads to immunosuppressive signaling and an aggressive breast cancer phenotype. XIAP antagonists are in clinical trials and these data suggest potential benefit in targeting XIAP to enhance immunotherapeutic efficacy in IBC therapy. FUNDING: DoDs-W81XWH-17-1-0297,W81XWH-20-1-0153, ACS Mission Boost Grants(GRD) Citation Format: Christophe Van Berckelaer, Steven Van Laere, Joseph Gerardts, Luc Dirix, Michael Morse, Mark Kockx, François Bertucci, Peter Van Dam, Gayathri R Devi. Xiap expression is associated with infiltration of cd163+ tumor-associated macrophages in the tumor micro-environment of inflammatory breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-04-07.

A Systematic Review: Does Insulin Resistance Affect the Risk and Survival Outcome of Breast Cancer in Women?

Currently, breast cancer is one of the insidious malignancies that evolves silently, eventually leading to mortality, and has been recorded as one of the leading causes of cancer-related deaths around the globe. It is evident from numerous research studies that the etiology of breast cancer is multifaceted, both on an individual and environmental level. Insulin resistance, commonly known as metabolic syndrome, has been related to a poor breast cancer prognosis. There is presently limited data on the clinical features of insulin-resistant breast cancer patients. The purpose of this study is to examine the association between metabolic syndrome and its components impacting the risk and the prognosis of breast cancer, including the clinicopathological variables in patients with newly diagnosed breast cancer with and without already established diabetes. The authors extracted data from PubMed, Google Scholar, Science Direct, and Embase, intending to study the connections between these two entities. Studies from worldwide were selected to analyze the association between breast cancer and insulin resistance, including mammogram screening practices in a region-wise manner. The ultimate objective is to raise awareness of this association among practitioners worldwide. After analyzing several reports that included observational studies, it is to be concluded that insulin resistance impacts breast cancer both in regards to increasing the risk as well as affecting the survival outcome.

Expression of Septin 2 and Her2/neu in Colorectal Cancer.

Colorectal cancer (CRC) is a common and lethal disease. Septin 2 belongs to the same class of GTPases as the RAS oncogenes influence the invasion and metastasis of many types of tumor cells. Furthermore, HER2/neu is involved in the tumor genesis and progression of various types of tumors. The role of both molecules is still questionable in CRC. The aim of the study is to examine the expression of septin 2 and Her2/neu in patients with CRC. The study was conducted on 2 groups; the first group consisted of 70 paraffin blocks for CRC patients and the second group was formed of 24 blocks from patients diagnosed as colorectal adenoma. For each adenoma and carcinoma case, a section was immunohistochemically stained using antihuman SEPT2 polyclonal antibody. For each carcinoma case, another section was immunostained using monoclonal anti-HER2/neu. The results were statistically analyzed and compared with the collected clinicopathologic data of the cases. For the carcinoma patients, there was a significant association between SEPT2 staining intensity and histologic type (P = 0.001) and grade (P < 0.001), tumor T (P = 0.001) and N (P = 0.011) stages and the presence of lymphovascular invasion (P < 0.001) and a significant association between Her2/neu immunoreactivity scores (IRSs) and histologic grade (P = 0.048), tumor T (P < 0.001) and N (P = 0.019) stages and the presence of perineural (P = 0.004) and lymphovascular (P = 0.003) invasion. In colonic adenoma patients, there was a significant relation between septin 2 IRSs and the grade of dysplasia in the adenoma (P < 0.001) and significant relation with its expression in carcinoma group (P < 0.001). A potential prognostic role of septin 2 and Her2/neu for patients with CRC is suggested as expression of both markers was associated with many important prognostic clinicopathologic variables in patients of CRC.

Alpha-L-Fucosidase Has Diagnostic Value in Prostate Cancer With "Gray-Zone PSA" and Inhibits Cancer Progression via Regulating Glycosylation.

BackgroundThis study aimed to explore the diagnostic value of alpha-l-fucosidase (AFU) in prostate cancer (PCa) patients with “gray-zone PSA” and to investigate the correlation between AFU expression and clinicopathological characteristics of PCa patients.MethodsThe level of AFU and other necessary clinicopathological variables of patients were retrieved from electronic medical records. The transcriptome profiling and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The protein level of AFU in tissue was assessed by immunohistochemistry (IHC). All the data were processed by appropriate analysis methods. The p-value of <0.05 was considered statistically significant.ResultsAFU showed ideal diagnostic value for PCa with prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/ml, and its optimal cutoffs were 19.5 U/L. Beyond this, low AFU expression was associated with high pathological grade, T stage and N stage, more postoperative residual tumors, and poor primary therapy outcome, as well as shorter progression-free interval. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis illustrated that FUCA1/FUCA2 exerted tumor-suppressive function by regulating the glycosylation.ConclusionsAFU (<19.5 U/L) could effectively distinguish the PCa from the patients with “gray-zone PSA”, and low expression of AFU was an independent unfavorable predictor for the clinicopathological characteristics of PCa patients.