Clinical Pathological Parameters Research Articles

Co-expression of High-mobility group box 1 protein (HMGB1) and receptor for advanced glycation end products (RAGE) in the prognosis of esophageal squamous cell carcinoma

Esophageal cancer is a malignant type of cancer with a high mortality rate. The aim of this study is to determine co-expression patterns of High-mobility group box 1 protein (HMGB1) and receptor for advanced glycation end products (RAGE) in ESCC (esophageal squamous cell carcinoma) conditions and their prognostic role in cancer progression. The expression of HMGB1 and RAGE in ESCC tissues has been analyzed using qRT–PCR and Western blotting. Co-localized expression patterns of HMGB1 and RAGE in ESCC tissues were determined using immunohistochemistry and analyzed for clinical-pathological parameters. Overall survival was performed based on co-expression of HMGB1 and RAGE proteins. A higher expression pattern of HMGB1, and RAGE was observed at mRNA and protein level in the ESCC group compared to the adjacent tissue group. Expression of HMGB1 was significantly correlated with lymph node, metastasis, lymphatic invasion, and venous invasion (p < 0.05). RAGE expression exhibited a significant correlation with venous invasion. Overall survival was significantly shorter (P < 0.05) in the patients with co-expression of HMGB1 and RAGE compared to the patients without co-expression. A significant difference in the overall survival was evident between the patients with co-expression of HMGB1 and RAGE and the patients without coexpression. HMGB1 and RAGE expression patterns were associated with aggressive metastatic characteristics of ESCC. The co-expression of HMGB1 and RAGE was correlated with shorter survival times. Results concluded the co-expression patterns of HMGB1 and RAGE exhibited a prognostic relevance in ESCC conditions.

CDX2 immunohistochemical expression in human colorectal adenocarcinoma and gastric adenocarcinoma: A comparative study

Background: Caudal-related home box gene two (CDX2) is home box domain containing transcription factor that is important in the development and differentiation of the intestine. Aim of the study: to examine the expression of Caudal-related home box gene two in a series of colorectal and gastric adeno carcinomas, and correlate its expression with different clinic pathological parameters including: tumor type grade stage and compare its expression between the two malignancies. Material and Method: this is a retrospective study of a total of fifty cases including twenty five cases of colorectal carcinomas and twenty five cases of gastric adenocarcinoma were collected from the histopathology laboratory department of gastroenterology and hepatology teaching in Baghdad (from January 2021 to January 2022); slides were prepared from paraffin blocks and stained with Hematoxylin and Eosin for histopathological revision and others were stained immunohistochemically with CDX2, CDX2 expression was semi-quantitatively scored. Correlation between clinic pathological parameters and CDX2 expression was done. Results: Regarding the twenty-five cases of colorectal adenocarcinoma: age range was (45-85) years,15 (60%) of cases were males, 10 (40%) of them were females, most common cases 23 (92%) were grade 2, and most common 18 (72%) of the cases were stage T3, most common cases 16 (64%) cases had no lymph node involvement (N0), all the cases showed positivity for or CDX2,17 (68%) of cases had CDX2 score (3) while 8 (32%) of them had CDX2 score (2). Regarding the twenty five cases of gastric adenocarcinoma: age range was (24-69) years,17 (68%) of were males, 8 (32%) of them were females, most common 14 (56%) of the cases were grade (2), and most common stage 20 (80%) of the cases were stage T3,most common cases 7 (28%) had no lymph node involvement (N0), most 15 (60%) of the cases showed positivity for or CDX2, 9 (36%) of cases had CDX2 score (1), 5 (20%) of cases showed score (2),1 (4%) of cases showed score (3), while 10 (40%) of the cases were negative for CDX2 (score 0). Conclusion: CDX2 marker is already proven as highly sensitive in colorectal adenocarcinoma. There was a significant correlation between CDX2 score and the site of the tumor (colorectal versus gastric).

Abstract 2772: A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses

Abstract Background: Lung cancer is the world's highest mortality and incidence rate of malignancy, and the prognosis survival rate is significantly lower than other tumors. A novel bio-physics based multi (pan)-cancer test technology named Cancer Differentiation Analysis Technology (CDA) has been developed and investigated for evaluating and monitoring lung cancer therapeutic responses. Methods: A total of 686 patients diagnosed with different sub-types of lung cancer were included in this study. CDA levels were concurrently measured in peripheral blood obtained from 686 patients during the treatment. According to the response evaluation criteria in solid tumors (RECIST) 1.1 standard, the efficacy of 686 patients after treatment was evaluated, and the diagnostic efficacy of CDA technology was evaluated by receiver operating characteristic (ROC) curve. Results: Clinical pathological parameters of the patients are listed in Table 1. The higher the CDA value, the worse the curative effect. CDA value of lung cancer in CR (complete response) group was significantly lower than that in other 3 groups (p&amp;lt;0.05). CDA value of adenocarcinoma lung cancer in CR group were significantly lower than that in SD (stable disease) group (p&amp;lt;0.05). For non - metastatic lung cancer, CDA value in CR group was significantly lower than that in SD group (p&amp;lt;0.05) The receiver ROC analysis showed that the area under curve (AUC) of lung cancer group, NSCLC group, adenocarcinoma lung cancer group, were 0.756, 0.772, and 0.792, respectively. The AUC of early lung cancer group, and non - metastatic lung cancer group were 0.794, and 0.851. Conclusions: CDA appears to have the ability to predict and monitor therapeutic responses to lung cancer surgery and chemotherapy treatments. In most cases, the CDA of CR patients is low, and there is a good correlation between CDA and curative effect in early lung cancer. CDA could be a potential candidate for evaluating lung cancer, especially for early stage lung cancer therapeutic response. Citation Format: Junjie Wu, Zixiu Zou, Xuedong Du, Yue Lin, Xing Tang, Jie Chen, Lan Peng, Chris Yu. A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2772.

Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion.

Long-tailed macaques are the predominant nonhuman primate species for the nonclinical safety testing of biopharmaceuticals. This species comprises 9 subspecies with Macaca fascicularis fascicularis naturally occurring in Southeast Asia. Since the 17th century, M. f. fascicularis also occurs on Mauritius. Cynomolgus macaques do not naturally occur in China, but are bred in many farms across the country. The current shortage in animal supply raises the question whether geographical animal origin matters and if animals from different geographical regions can be combined on a drug development program or even a single experiment. This article reviews geographical animal origin in relation to selected endpoints that are relevant in nonclinical drug safety testing. Animals from different countries within Asia mainland do not appear to show any meaningful difference. Very little data are available for animals from Asia island. Mauritian animals show consistent differences from Asian animals in several clinical and anatomical pathology parameters. For developmental parameters, animals from Mauritius and Asia are comparable with the exception that Mauritian animals mature faster. In the authors' view, differences between the geographical clusters can be accounted for as long as baseline and reference data are available.

Immunohistochemical expression of Forkhead Box (Fox) A1 and P53 in epithelial ovarian cancer

Background: Ovarian cancer (OC) is the fifth cause of cancer mortality in females. There were an estimated 300,000 new cases of OC diagnosed worldwide in 2018, corresponding to 3.4% of all cancer cases among women. The high mortality rate of OC attributed to asymptomatic growth of the tumor leads to its diagnosis at advanced stages. About 85% - 90% of OC are epithelial including serous, endometrioid, clear cell, and mucinous carcinoma. Aim: To study the immunohistochemical (IHC) expression of FOX A1 and p53 in epithelial OC and its association with prognostic indicators such as age, tumor size, stage, grade, and histological type. Materials and methods: The study included 52 cases with EOC from the pathology department, faculty of medicine, Aswan, and Sohag Universities, in the period from January 2017 to December 2019. This study involved 52 patients with OC and a median age of 53 years. Different histological types were included as 37 serous, 12 mucinous, 1 case endometroid 2 cases clear cell OC. The study cases were classified into 22 Grade I, 16 Grade II, and 20 Grade III. About 22 cases were at stage I, 9 at stage II, 11 at stage III, and 10 at stage IV. Tissue sections were stained using the IHC technique with FOX A1 at a dilution of 1:100 and p53 at 1:100. Results: A statistically significant correlation was found between FOX A1 expression and advanced patient's age, high grade, advanced stage, ruptured capsule, and ascites, regardless of tumor laterality. No significant association was found between p53 immunoexpression and the same clinic-pathological parameters although p53 was associated with serious type. Conclusion: FOX A1 immunoexpression in EOC is considered a poor prognostic factor in EOC. FOX A1 could be a potential therapeutic target and prognostic marker in EOC.

A Nomogram for Predicting Early Recurrence in Patients with High-Grade Gliomas

The objective of the study was to develop a nomogram to predict early recurrence of high-grade glioma (HGG) based on clinical pathology, genetic factors, and magnetic resonance imaging parameters. One hundred fifty-four patients with HGG were classified into recurrence and nonrecurrence groups based on the pathological diagnosis and Response Assessment in Neuro-Oncology criteria. Clinical pathology information included age, sex, preoperative Karnofsky performance status scores, grade, and cell proliferation index (Ki-67). Gene information included P53, isocitrate dehydrogenase 1 (IDH1), O6-methylguanine-DNA methyltransferase, and telomerase reverse transcriptase expression status. All patients underwent baseline magnetic resonance imaging before treatment, including T1-weighted imaging, T2-weighted imaging, contrast-enhanced T1WI, fluid attenuated inversion recovery, and diffusion-weighted imaging examinations. Tumor location, single/multiple tumors, tumor diameter, peritumoral edema, necrotic cyst, hemorrhage, average apparent diffusion coefficient value, and minimum apparent diffusion coefficient values were evaluated. Univariate and multivariate logistic regression analyses were used to determine the predictors of early recurrence and build a nomogram. Univariate analysis showed that the number of tumors (odds ratio [OR], 0.258; 95% confidence interval [CI]: 0.104, 0.639; P=0.003) and peritumoral edema (OR, 0.965; 95% CI: 0.942, 0.988; P=0.003; mean in the recurrence group= 22.04±17.21mm; mean in the nonrecurrence group= 14.22±12.84mm) were statistically significantly different in patients with early recurrence. Genetic factors associated with early recurrence included IDH1 (OR, 4.405; 95% CI: 1.874, 10.353; P=0.001) and O6-methylguanine-DNA methyltransferase (OR, 2.389; 95% CI: 1.234, 4.628; P=0.010). Multivariate logistic regression analysis revealed that the number of tumors (OR, 0.227; 95% CI: 0.084, 0.616; P=0.004), peritumoral edema (OR, 0.969; 95% CI: 0.945, 0.993; P=0.013), and IDH1 (OR, 4.200; 95% CI: 1.602, 10.013; P=0.004) were independent risk factors for early recurrence. The nomogram showed the highest net benefit when the threshold probability was less than 60%. A nomogram prediction model can effectively aid in clinical treatment decisions for patients with newly diagnosed HGG.

Clinical-Pathological Evaluation and Prognostic Analysis of 228 Merkel Cell Carcinomas Focusing on Tumor-Infiltrating Lymphocytes, MCPYV Infection and ALK Expression

Merkel cell carcinoma is a rare and aggressive primary neuroendocrine carcinoma of the skin, whose pathogenesis can be traced back to UV radiation damage or Merkel cell polyomavirus (MCPyV) infection. Despite some improvements on the characterization of the disease partly due to its increased incidence, crucial pathogenetic and prognostic factors still need to be refined. A consecutive series of 228 MCC from three hospitals in Turin was collected with the aim of both analyzing the apparent increase in MCC incidence in our area and investigating the distribution and prognostic role of clinical-pathological parameters, with a focus on MCPyV status, ALK tumor expression and tumor infiltrating lymphocytes (TILs). Review of morphology and conventional immunohistochemical staining was possible in 191 cases. In 50 cases, the expression of the novel neuroendocrine marker INSM1 was additionally assessed. Fourteen cases of MCC of unknown primary skin lesion were identified and separately analyzed. While confirming an exponential trend in MCC incidence in the last decades and providing a description of histological and cytological features of a large series of MCC, the present study concludes that 1) INSM1 is a highly sensitive marker in both skin and lymph node primary MCC; 2) positive MCPyV status, brisk TILs and lower tumor size and thickness are independent positive prognostic parameters, and the combination of the former two may provide a novel tool for prognostic stratification; 3) ALK is expressed 87% of MCC and associated with positive viral status, and could represent a prognostic biomarker, if validated in larger series.

MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy

Abstract BACKGROUND AND AIMS Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target. METHOD A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions. RESULTS Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049). CONCLUSION The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.

Tissue Proteomics and Custom-Made Transcriptomics Analysis Tool Revel PPP1R12B, FBLN5, CRIP2, and POSTN as Potential Prognostic Biomarkers in Prostate Cancer

PURPOSE Prostate cancer (PCa) is a progressive disease involving multiple molecular alterations. The Gleason Grade (GG) is used as an aid for physicians to evaluate the prognosis of men with PCa using samples from prostate tissues. However, some PCa that are histo-pathologically grouped in the same GGs can differ significantly in outcome. The aim of this study was to identify molecular biomarkers that could behave independently from GG and other clinical-pathological variables (age, GG and TMPRSS2-ERG fusion status) that can improve risk prediction of PCa. METHODS An in-depth proteomics analysis (LC/ESI-MS/MS) was performed on human prostate adenocarcinoma and benign prostate hyperplasia (BPH) tissues. Protein candidates enriched in PCa vs BPH were further evaluated in-silico using a custom-made pipeline. For this purpose, seven publicly available transcriptomic PCa datasets (ntotal = 875) were selected, and differential expression analyses were performed in R. A Shiny-based tool was then built to execute the search and to allow visualization across multiple datasets. Further multivariable analyses were performed using clinical-pathological parameters as covariates. RESULTS Proteomics analysis yielded a list of 89 proteins enriched in PCa compared with BPH. 58 showed high expression in PCa datasets and nine of those, showed significant association with higher risk of death. Further, when performing a multivariable Cox proportional-hazard model including age, GG and TMPRSS2-ERG fusion status, PPP1R12B, FBLN5, CRIP2, and POSTN displayed associations with poor prognosis, independently from the other co-variates (HR = 1.5, P = .0084; HR = 1.34, P = .035; HR = 1.36, P = .016 and HR = 1.4, P = .0028, respectively). CONCLUSION PPP1R12B, FBLN5, CRIP2, and POSTN proteins were enriched in PCa human tissues. Our custom pipeline revealed increased expression of these genes across multiple PCa datasets and significant association with increased risk of death, independent from known risk factors and predictors of PCa prognosis. Thus, these factors rise as potential prognostic markers.

Initial satisfying experience of total retroperitoneal laparoscopic radical nephroureterectomy: a retrospective comparative research.

BackgroundRadical nephroureterectomy (RNU) is the principal method for treatment of high-risk upper urinary tract urothelial carcinoma (UTUC). The transperitoneal approach is associated with poor disease progression, but the distal ureter-bladder cuff (DUBC) resection through retroperitoneal laparoscopic approach is difficult. This study proposed a modulated RNU technique, namely, total retroperitoneal laparoscopic radical nephroureterectomy (tRLRNU), with its advantages of DUBC resection and requiring fewer trocars etc. The efficiency, safety, and short-term impacts were retrospectively compared with total transperitoneal laparoscopic radical nephroureterectomy (tTLRNU).MethodsTotal of 12 patients who received tRLRNU and 28 patients who received tTLRNU were enrolled. The choice of surgical approach was random and their data were retrospectively analyzed. During tRLRNU, the laparoscope was versed towards the caudal direction and a retroperitoneal laparoscopic ureterectomy was performed. The bladder cuff was entirely transected and the bladder incision was sutured. The tRLRNU cases were compared with the tTLRNU cases in terms of general clinical data, pathologic parameters, peri-operative parameters, adjuvant therapy, and short-term outcomes. The independent samples t-tests, chi-square tests, and Fischer exact tests were used to analyze the differences.ResultsThere were no significant differences in the basic patient characteristics between the 2 groups. The data were comparable. There were significantly fewer trocars utilized in tRLRNU group compared to tTLRNU group (P=0.0008). tRLRNU group experienced less blood loss (98.33±61.32 versus 170.71±121.32 mL; P=0.017), smaller drainage volume (182.08±163.60 versus 1,924.82±3,370.02 mL; P=0.011), and shorter extubation time (5.67±1.07 versus 8.57±6.96 days; P=0.040) compared to tRLRNU group. There were no statistically differences in the other peri-operative parameters, including whole operation time, transfusion, visceral and vascular injuries, open conversion, post-operative bleeding, recovery time of intestinal function, and discharge time. The patient outcomes in tTLRNU group at 6 months were significantly worse than that of tRLRNU group by comparing progression-free survival, progression survival and mortality (P=0.039).ConclusionsThe tRLRNU was potentially safer, minimally invasive, and more effective compared to the tTLRNU. Due to the small sample size, short follow-up time and no randomization of the study, future comparative studies are warranted to further analyze long-term outcomes of tRLRNU.

Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1, HSPB1, DDB1 and 14-3-3ζ/δ Interaction

PURPOSE Prostate cancer (PCa) is the second most common type of cancer in men and the sixth leading cause of cancer-related death in men worldwide. The discovery of new therapeutic avenues in PCa, and the development of effective drugs in the era of personalized medicine, would greatly benefit from the field of proteomics. We have previously shown the anti-tumoral role of Heme oxygenase 1 (HO-1) in PCa. METHODS In this work, we undertook a mass spectrometry-based proteomics study to assess whether in PCa cells and under oxidative stress conditions, HO-1 could interact with proteins previously documented to have nuclear localization. RESULTS Among the HO-1 interactors, we identified 11 proteins with nuclear localization. Significant and positive correlation between HMOX1 and six of those genes was observed, using the GSE70770 dataset. Alternatively, HMOX1 and YWHAZ showed negative correlation. High expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with an increased relapse-free survival (RFS) in PCa patients through univariable analyses. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, by using a prognostic risk score model, a decrease in RFS for patients with higher scores of this signature was observed. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. HSPB1, DDB1 and YWHAZ independence from PCa clinic-pathological parameters was confirmed through multivariable analyses. Moreover, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (YWHAZ encoding gene) interaction. CONCLUSION Herein, we report novel interactions between HO-1 and HSPB1, DDB1 and 14-3-3ζ/δ, highlighting their clinical relevance in PCa.

Modulation of Long Non-coding RNAs by Different Classes of Secondary Metabolites from Plants: A Mini-review on Antitumor Effects.

The broad pharmacological spectrum of plants is related to their secondary metabolism, which is responsible for the synthesis of different compounds that have multiple effects on cellular physiology. Among the biological effects presented by phytochemicals, their use for the prevention and treatment of cancer can be highlighted. This occurs due to several mechanisms of antitumor action demonstrated by these compounds, including regulation of the cell signaling pathways and inhibition of tumor growth. In this way, long non-coding RNAs (lncRNAs) appear to be promising targets for the treatment of cancer. Their deregulation has already been related to a variety of clinicalpathological parameters. However, the effects of secondary metabolites on lncRNAs are still restricted. For this reason, the present review aimed to gather data on phytochemicals with action on lncRNAs in order to confirm their possible antitumor potential. According to the literature, terpenoid and flavonoid are the main examples of secondary metabolites involved with lncRNAs activity. In addition, the lncRNAs H19, CASC2, HOTAIR, NKILA, CCAT1, MALAT1, AFAP1-AS1, MEG3, and CDKN2B-AS1 can be highlighted as important targets in the search for new anti-tumor agents since they act as modulating pathways related to cell proliferation, cell cycle, apoptosis, cell migration and invasion. Finally, challenges for the use of natural products as a commercial drug were also discussed. The low yield, selectivity index and undesirable pharmacokinetic parameters were emphasized as a difficulty for obtaining these compounds on a large scale and for improving the potency of its biological effect. However, the synthesis and/or development of formulations were suggested as a possible approach to solve these problems. All of these data together confirm the potential of secondary metabolites as a source of new anti-tumor agents acting on lncRNAs.

Vitronectin, a Novel Urinary Proteomic Biomarker, Promotes Cell Pyroptosis in Juvenile Systemic Lupus Erythematosus.

Objective Identifying new markers of juvenile systemic lupus erythematosus (JSLE) is critical event to predict patient stratification and prognosis. The aim of the present study is to analyze alteration of urinary protein expression and screen potential valuable biomarkers in juvenile systemic lupus erythematosus (JSLE). Methods The urine was collected from the patients with or without JSLE and detected by mass spectrometry to analyze proteomic changes. ELISA was used to verify the Vitronectin (VTN) changes in a new set of patients. The clinical correlation was performed to analyze between VTN and clinical pathological parameters. WB and ELISA were used to analyze VTN-mediated cell pyroptosis. Results Herein, we have identified a group of 105 differentially expressed proteins with ≥1.3-fold upregulation or ≤0.77-fold downregulation in JSLE patients. These proteins were involved in several important biological processes, including acute phase inflammatory responses, complement activation, hemostasis, and immune system regulation through Gene Ontology and functional enrichment analysis. Interestingly, urinary ephrin type-A receptor 4 (EPHA4) and VTN were significantly reduced in both inactive and active JSLE patients, and VTN treatment in THP-1 derived macrophages led to a significant increased cell pyroptosis by activation of Nod-like receptor family protein 3 (NLRP3) inflammasomes, resulting in caspase-1 activation, cleaved gasdermin D (GSDMD), and IL-18 secretion. Most importantly, the urinary VTN was also linearly correlated with clinical characteristics of JSLE, implying that VTN could be a specific diagnostic biomarker to distinguish inactive and active JSLE. Conclusion This study provided a novel role of VTN in pyroptosis in JSLE through the urinary proteomic profile for JSLE, which could be a nonintrusive monitoring strategy in clinical diagnosis.

Upregulation of Synuclein-γ and Snai1 Contributes to Poor Clinical Prognosis in Oral Squamous Cell Carcinoma Patients.

Synuclein-γ (SNCG) and Snai1 play an important role in the occurrence and development of different types of malignant tumors. However, the association between SNCG and Snai1 and the effect of their combination on oral squamous cell carcinoma (OSCC) are unknown. The purpose of this study was to assess the expression of SNCG and Snai1 in OSCC tissues and their role in the genesis, development, diagnosis, and prognosis of OSCC. In this study, we first analyzed the Gene Expression Omnibus (GEO) database to determine the expression of SNCG and Snai1 in OSCC. And we also evaluated the correlation between the expression of SNCG and Snai1 and clinical pathological parameters in OSCC from The Cancer Genome Atlas (TCGA) database. Then, the expression of SNCG and Snai1 in OSCC and its adjacent tissues in our experimental cohort were detected by qRT-PCR, Western blot, and immunohistochemistry, and the relationship between their expression and clinical pathological parameters were analyzed. At the same time, the correlation between the expression of SNCG and Snai1 was analyzed from the TCGA, GEO database, and our experimental cohort. Next, the ROC curves were constructed to explore the diagnostic value of SNCG and Snai1 in OSCC. Finally, the survival curves were drawn, and the univariate and multivariate Cox regression analyses were performed to determine the prognostic value of SNCG and Snai1 in OSCC. The study found that SNCG and Snai1 were highly expressed in OSCC tissues. The expression of SNCG was related to the differentiation of OSCC, while that of Snai1 was related to the T stage, lymph node metastasis, clinical stage, and differentiation. Besides, the expression of SNCG in OSCC was positively correlated with that of Snai1. In addition, we also found that SNCG and Snai1 could well distinguish OSCC patients from normal people; especially, the combined diagnosis of SNCG and Snai1 had a better effect, with a specificity up to 96.67%. Moreover, SNCG-negative/Snai1-negative OSCC patients had the best prognosis. Multivariate analysis displayed that SNCG-positive expression was an independent risk factor for prognosis in OSCC patients. The results of this study strongly suggested that SNCG and Snai1 might have a cooperative effect in the occurrence and development of OSCC. They may become new markers for the diagnosis and prognosis of OSCC.

Morphologic Spectrum of Breast Carcinoma and Correlation of Hormone Receptors and Her2/Neu Status with Clinic-Pathologic Parameters at a Tertiary Care Hospital

Background: After cardiovascular problems, cancer is the 2nd biggest cause of mortality globally. Globally, breast cancer is recognized as the second most prevalent cancer in general, the most prevalent cancer in women, and the 5th major cause of cancer-related death. Objectives: To study the Morphologic Spectrum of Breast Carcinoma and correlation of hormone receptors and HER2/neu status with clinic-pathologic parameters Methods: A total of 97 consecutive cases of modified radical mastectomy were evaluated in the department of histopathology, Rehman Medical Institute Peshawar from February 2019 to December 2020. Expression of PR, ER and Her2/neu were scored similar to College of American Pathologist’s (CAP) guidelines. The analysis of data was done by using SPSS version. Results: Mean age of presentation was 49.6 years. The most prevalent histological subtype was invasive carcinoma of no particular type (72.2%). Grade II tumors were most frequent (43.3%). Lymphovascular and perineural invasion were present in 53.6% and 40.2% of cases respectively. Pathologic stage pT2 was most frequent (56.7%). Macrometastasis was noted in 61.8% of cases. ER and PR showed positivity in 59.8% and 51.5% of cases and Her2/neu was over expressed in 30.9% of cases. ER positivity inversely correlated with Her2/neu but directly with tumor size. Strong association was found between ER/PR positivity and HER2/neu with histologic grade. Conclusion: Our study showed a diverse spectrum of special type carcinomas, none of which showed HER2/neu over expression. Majority of our patients belong to a younger age group and presented with advanced disease. Triple negative breast cancer (TNBC) was commonest in our population after luminal A. HER2/neu overexpression was limited to grade 2 and 3 of invasive ductal carcinoma Keywords: Morphologic Spectrum; Breast Carcinoma; Hormone receptors

Mesangial cell-derived tenascin-C contributes to mesangial cell proliferation and matrix protein production in IgA nephropathy.

Tenascin-C (TNC), a non-structural extracellular matrix glycoprotein, is transiently expressed during development or after injury, playing an important role in injury and repair process. The potential role of TNC in the pathogenesis of IgA nephropathy (IgAN) remains to be clarified. Immunohistochemistry staining for TNC was conducted on paraffin-embedded slices from renal biopsies of 107 IgAN patients, and correlation analysis was made between mesangial TNC expression and clinic-pathological parameters. In situ hybridization for TNC mRNA was further performed to figure out the cells that express TNC within glomeruli. In vitro experiments were also carried out on mouse mesangial cells (SV40 MES13) to elucidate the effect of TNC on mesangial cells. TNC was expressed in the mesangial area of IgAN, as well as in fibrotic regions. Correlation analysis showed that higher mesangial TNC was associated with higher level of proteinuria, lower estimated glomerular filtration rate and more serious pathological lesions (MEST score). In situ hybridization revealed that abundant TNC mRNA expression was observed in the affected glomeruli of IgAN, but not in minimal change disease. Moreover, TNC mRNA co-localized with PDGFRβ mRNA, but not with PODXL mRNA, suggesting that TNC mRNA was expressed in the mesangial cells within glomeruli in IgAN. In vitro experiments showed that exogenous TNC promoted matrix protein production and mesangial cell proliferation, which was attenuated by an epidermal growth factor receptor inhibitor. Taken together, these results suggest that mesangial cell-derived TNC contributes to mesangial matrix expansion and mesangial cell proliferation, which is a potential therapeutic target in IgAN.

Detection of plasma exosomal miRNA-205 as a biomarker for early diagnosis and an adjuvant indicator of ovarian cancer staging

BackgroundOvarian cancer (OC) is one of the serious threats to the health of women worldwide, and accurate biomarkers are urgently demanded for early diagnosis of OC. We have previously confirmed that miR-205 promotes the invasion and metastasis of OC cells by inhibiting the expression of the tumor suppressor gene TCF21. In this study, we used liquid biopsy technology to detect the expression levels of the four genes, miR-205, CA125, HE4 and TCF21, in the exosomes of plasma of OC patients. Combined with analysis of clinicopathological parameters of OC patients, we aimed to provide efficient and non-invasive laboratory biomarkers for early diagnosis of OC.Methods36 OC patients who were diagnosed in local hospitals from September 2020 to July 2021 were selected as OC group, 31 cases of surgically diagnosed with ovarian benign lesions were selected as benign group, and 32 healthy people who underwent physical examination during the same period were selected as a control group. We employed transmission electron microscope (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA) to identify biomarkers in the exosomes extracted from plasma of the three groups. The RNA levels of miR-205, CA125, HE4 and TCF21 genes in plasma exosomes were detected by real-time quantitative PCR (qRT-PCR) method. We used clinical pathological parameters and the Receiver Operating Characteristic (ROC) curves to evaluate the diagnostic efficacy for the genes detected in plasma exosomes.ResultsWe found that the expression level of miR-205 in plasma exosomes of the OC group was significantly higher than that of the benign and control groups (P < 0.05), and the level of miR-205 was elevated during the III-IV periods of OC and lymph node metastasis.ConclusionThe level of miR-205 in plasma exosomes is a valuable tumor biomarker to improve OC diagnosis.

Epithelial-mesenchymal transition related to bone invasion in oral squamous cell carcinoma

IntroductionBone invasion is an important prognostic factor in oral squamous cell carcinoma, leading to a lower survival rate and the use of aggressive treatment approaches. Epithelial-mesenchymal transition (EMT) is possibly involved in this process, because it is often related to mechanisms of cell motility and invasiveness. This study examined whether a panel of epithelial-mesenchymal markers are present in cases of oral squamous cell carcinoma with bone invasion and whether these proteins have any relationship with patients’ clinical-pathological parameters and prognostic factors. MethodsImmunohistochemical analysis of E-cadherin, twist, vimentin, TGFβ1, and periostin was performed in paraffin-embedded samples of 62 oral squamous cell carcinoma cases. ResultsThe analysis revealed that most cases (66%) presented with a dominant tumor infiltrative pattern in bone tissue, associated with lower survival rates, when compared with cases with a dominant erosive invasion pattern (P = 0.048). Twenty-seven cases (43%) expressed markers that were compatible with total or partial EMT at the tumor-bone interface. There was no association between evidence of total or partial EMT and other demographic or prognostic features. E-cadherin-positive cases were associated with tobacco smoking (P = 0.022); vimentin-positive cases correlated with tumors under 4 cm (P = 0.043). Twistexpression was observed in tumors with a dominant infiltrative pattern (P = 0.041) and was associated with the absence of periostin (P = 0.031). ConclusionWe observed evidence of total or partial EMT in oral squamous cell carcinoma bone invasion. The transcription factor twist appears to be involved in bone invasion and disease progression.

TGF-\u03b21 induced deficiency of linc00261 promotes epithelial\u2013mesenchymal-transition and stemness of hepatocellular carcinoma via modulating SMAD3

Emerging evidence suggests that long non-coding RNAs (lncRNAs) play important roles in the metastasis and recurrence of hepatocellular carcinoma (HCC). A kinds of lncRNAs were found to be involved in regulating epithelial–mesenchymal transition (EMT) or stem-like traits in human cancers, however, the molecular mechanism and signaling pathways targeting EMT and stemness remains largely unknown. Previously, we found that linc00261 was down-regulated in HCC and associated with multiple worse clinical pathological parameters and poor prognosis. Here, we show that linc00261 was down-regulated in TGF-β1 stimulated cells, and forced expression of linc00261 attenuated EMT and stem-like traits in HCC. Linc00261 also inhibited the tumor sphere forming in vitro and decreased the tumorigenicity in vivo. Furthermore, we revealed that linc00261 suppressed the expression and phosphorylation of SMAD3 (p-SMAD3), which could be core transcriptional modulator in TGF-β1 signaling mediated EMT and the acquisition of stemness traits. A negative correlation between linc00261 and p-SMAD3 was determined in HCC samples. Conclusion: Our study revealed that linc00261 suppressed EMT and stem-like traits in HCC cells by inhibiting TGF-β1/SMAD3 signaling.

Filamin-A expression in laryngeal squamous cell carcinoma and its clinical significance.

Laryngeal squamous cell carcinomas (LSCCs) are tumours with a high incidence of treatment failure and recurrence. Recent strategies to improve the five-year survival rate and to decrease the rates of recurrence and metastases did not improve outcomes significantly. Research efforts in recent years have started focusing on discovering biomarkers of prognosis and management in LSCCs. Filamin-A reportedly has been associated with metastatic disease in a recent study. Analysis of this protein's expression in LSCCs is lacking in the literature. This study analysed the expression of filamin-A, using immunohistochemistry, in a tissue microarray of 80 cases of laryngeal squamous cell cancers. Clinical-pathological parameters were analysed according to filamin-A expression in the tissue microarray. Furthermore, a review of possible mechanisms of this protein in cancer, in general, was presented, along with a review of the protein's expression in other head and neck tumours. A significant majority of laryngeal squamous cell cancers exhibited positive expression of filamin-A protein. All the filamin-A positive tumours expressed it in their cytoplasm. Significant correlation between filamin-A expression and grade, stage, lymph node status and metastases were found. The above may suggest an important role for filamin-A in LSCCs. Overall, filamin-A expression in laryngeal cancer is in line with evidence seen in other head and neck cancers. Further studies are in order to pinpoint the exact role of this protein in LSCCs, and its possible utilization in the management of these difficult-to-treat tumours.