Poor Tumor Differentiation Research Articles

Potential predictors for CDX2 expression loss and mismatch repair deficiency in colorectal cancer.

CDX2 expression loss is commonly associated with mismatch repair deficiency (dMMR) in colorectal cancer (CRC). However, there are only a few studies that have attempted to correlate CDX2 expression loss with specific MMR genes (MLH1, MSH2, MSH6, PMS2). This is a retrospective study of 327 patients who underwent surgery due to CRC. Nine patients (2.9%) had two synchronous CRCs, making the total sample 336 CRC. Histopathological data such as tumor type, tumor grade, perineural, lymphatic, and vascular invasion, pT stage, pN stage, peritumoral and intratumoral lymphocytic infiltration were collected and recorded in the database. After immunohistochemical analysis, CDX2 expression, MLH1, MSH2, MSH6, and PMS2 deficiency were also recorded. CDX2 expression loss was detected in 19 out of 336 CRCs (5.9%) and was associated with ascending colon CRC, partially mucinous adenocarcinoma, poorly differentiated carcinoma, and dMMR. Forty-four (13.1%) of CRCs were dMMR. We found a statistically significant association between CDX2 expression loss and MLH1 and PMS2 deficiency. Considering that most expression phenotypes include pairs of MMR genes, we analyzed MLH1/PMS2 and MSH2/MSH6 as heterodimers. Analysis of heterodimers showed a similar result, namely, that MLH1/PMS2 heterodimer deficiency was significantly associated with CDX2 expression loss. We also constructed a regression model for CDX2 expression loss and for dMMR. Poor tumor differentiation and MLH1/PMS2 heterodimer deficiency have been identified as potential predictors for CDX2 expression loss. CRC in the ascending colon and CDX2 expression loss have been identified as positive potential predictors of dMMR with rectal cancer as negative potential predictor of dMMR. Our study showed a significant association between CDX2 expression loss and MLH1 and PMS2 deficiency in CRC. We also managed to produce a regression model for CDX2 expression and showed that poor tumor differentiation and MLH1/PMS2 heterodimer deficiency are independent factors for CDX2 expression loss. We were the first to include CDX2 expression in a regression model for dMMR and showed that CDX2 expression loss can be used as a predictive factor for dMMR, which should be confirmed by further studies.

Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295min, p = 0.009), blood loss (100 vs. 300ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR1.02, p = 0.002), poor tumor differentiation (HR3.05, p = 0.004), and (y)pT4b stage (HR2.35, p = 0.035) were independent risk factors for disease-free survival. LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.

Tumores neuroendócrinos pancreáticos: revisão histopatológica

Introduction: Pancreatic neuroendocrine tumors are considered rare. They are classified into functioning and non-functioning. Objective: To define and classify pancreatic neuroendocrine tumors according to their histopathological and immunohistochemical evaluation, associated with diagnostic criteria. Method: This is a narrative review of publications found in PubMed, SciELO and Google Scholar. Results: These tumors can be well or poorly differentiated and have distinct microscopic characteristics. Well-differentiated cells are small in shape, have uniform round or oval nuclei, finely granular cytoplasm indicating strong secretory capacity, and maintain the organoid structure. Presence of tumor necrosis, increased mitotic activity and high Ki-67 index indicate a high probability of neuroendocrine neoplasia. Chromogranin A and synaptophysin favor the diagnosis of well-differentiated. The positive staining of BCL 10 together with the absence of expression of chromogranin A and synaptophysin show poor tumor differentiation. The presence of positive staining for hormone expressions does not define the tumor as functioning. Conclusion: There was an increase in the diagnosis of pancreatic neuroendocrine tumors with the use of imaging techniques and awareness of the disease. Histopathological analysis with immunohistochemistry, especially when there are consuming symptoms, can indicate the type of carcinoma and lead to the most appropriate treatment.

LOXL2 promotes tumor proliferation and metastasis by FAK/Src signaling in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma is the most common malignant tumor of the upper gastrointestinal tract, which is prone to metastasis and has a poor prognosis. Lysine oxidase-like protein 2 (LOXL2) is an important intracellular protein that is highly expressed in a variety of tumors, leading to reduced patient survival. Studies have shown that LOXL2 is closely associated with tumor metastasis. However, the effect of LOXL2 on the biological function of esophageal squamous cell carcinoma (ESCC) and its related mechanisms are not fully understood. This study aimed to evaluate the potential prognostic and treatment value of LOXL2 in patients with ESCC. ResultsThe expression of LOXL2 was higher in ESCC tissues than in adjacent tissues. Positive LOXL2 expression was associated with poor tumor differentiation, lymph node metastases, and poor prognosis in ESCC patients. LOXL2 is an independent prognostic risk factor for ESCC. In vitro experiments showed that LOXL2 significantly promoted ESCC cell proliferation, migration, and invasion ability. LOXL2 altered the expression of the EMT marker, upregulating the mesenchymal marker (Snail) and downregulating the epithelial marker (E-cadherin). Mechanistically, LOXL2 induces EMT in esophageal squamous cell carcinoma by increasing FAK and SRC phosphorylation levels. ConclusionsTaken together, LOXL2 regulates the FAK/Src signaling pathway to promote malignant biological behavior and EMT process in ESCC cells. LOXL2 is a marker of poor prognosis, and LOXL2 could be a promising therapeutic target for the treatment of esophageal squamous carcinoma.How to cite: Liu Y, Liu X, Chen F, et al. LOXL2 promotes tumor proliferation and metastasis by FAK/Src signaling in esophageal squamous cell carcinoma. Electron J Biotechnol 2023;63. https://doi.org/10.1016/j.ejbt.2023.01.002.

Cell-free DNA as a prognostic and predictive biomarker in resectable distal common bile duct cancer.

Cell-free DNA (cfDNA) as an oncological biomarker has drawn much attention in recent years, but very limited effort has been made to investigate the prognostic values of cfDNA in distal common bile duct (CBD) cancer. Plasma cfDNA was measured in 67 patients with resectable distal CBD cancer. Survival outcomes and the correlation of cfDNA with other conventional prognostic factors were determined. cfDNA levels were significantly higher in female patients, and those with poor tumor differentiation, abnormal serum carcinoembryonic antigen (CEA) level, and stage III cancer. The significant prognostic factors included a high cfDNA level (>8955 copies/mL), abnormal serum CEA level, stage III cancer, and positive resection margins. Compared with patients with high cfDNA level, those with lower cfDNA level (≤8955 copies/mL) had significantly better overall survival outcomes (74.4% vs 100% and 19.2% vs 52.6%, for 1- and 5-year survival rates, respectively, p = 0.001). The cfDNA level, perineural invasion, CEA level, and radicality were identified as independent prognostic factors for distal CBD cancer after multivariate analysis. Circulating cfDNA levels play a significant role in predicting the prognosis and survival outcome for resectable distal CBD cancer. Furthermore, acting as a promising liquid biopsy, cfDNA could serve as a prognostic and predictive biomarker in combination with current conventional markers to improve diagnostic and prognostic efficacy.

The Japanese 5-5-500 Rule Predicts Prognosis of Hepatocellular Carcinoma After Hepatic Resection.

The 5-5-500 rule has been proposed to increase the candidates of liver transplantation for patients with hepatocellular carcinoma with reasonable recurrence rates. However, the clinical significance of the 5-5-500 rule in patients who underwent hepatic resection for hepatocellular carcinoma has not been fully investigated. The study comprised 206 patients who had undergone primary hepatic resection for hepatocellular carcinoma between 2008 and 2018. We retrospectively investigated prognostic significance of the 5-5-500 rule and disease-free, as well as overall, survival and further prognostic stratification using inflammatory-based biomarkers. 132 patients (64%) were classified within the 5-5-500 rule, while 74 patients (36%) were classified outside the 5-5-500 rule. Among the patients outside the 5-5-500 rule, 62 patients had tumors greater than 5 cm, and 23 patients showed serum AFP levels greater than 500 ng/ml. In the multivariate analysis, being female (p<0.01), HBs-Ag positive (p<0.01), having an ICGR15 ≥15% (p=0.03), and being outside the 5-5-500 rule (p=0.01) were independent and significant predictors of disease-free survival, while being HBs-Ag positive (p=0.04), having poor tumor differentiation (p=0.03), and residing outside the 5-5-500 rule (p=0.01) were independent and negative predictors of overall survival. Elevated CRP-to-albumin ratio was associated with poor overall survival in the patients outside the 5-5-500 rule, but not in patients within the 5-5-500 rule (p=0.17). The 5-5-500 rule can be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. CRP-to-albumin ratio might be useful to stratify the outcomes in patients outside the 5-5-500 rule.

What Is Known about Breast Cancer in Young Women?

Breast cancer (BC) is the second leading cause of cancer-related death in women under the age of 40 years worldwide. In addition, the incidence of breast cancer in young women (BCYW) has been rising. Young women are not the focus of screening programs and BC in younger women tends to be diagnosed in more advanced stages. Such patients have worse clinical outcomes and treatment complications compared to older patients. BCYW has been associated with distinct tumour biology that confers a worse prognosis, including poor tumour differentiation, increased Ki-67 expression, and more hormone-receptor negative tumours compared to women >50 years of age. Pathogenic variants in cancer predisposition genes such as BRCA1/2 are more common in early-onset BC compared to late-onset BC. Despite all these differences, BCYW remains poorly understood with a gap in research regarding the risk factors, diagnosis, prognosis, and treatment. Age-specific clinical characteristics or outcomes data for young women are lacking, and most of the standard treatments used in this subpopulation currently are derived from older patients. More age-specific clinical data and treatment options are required. In this review, we discuss the epidemiology, clinicopathologic characteristics, outcomes, treatments, and special considerations of breast cancer in young women. We also underline future directions and highlight areas that require more attention in future studies.

The synergized diagnostic value of VTQ with chemokine CXCL13 in lung tumors.

Virtual Touch Tissue Quantification (VTQ) offers several advantages in the diagnosis of various lung diseases. Chemokine expression levels, such as CXCL13, play a vital role in the occurrence and development of tumors and aid in the diagnosis process. The purpose of this study was to evaluate the combined value of VTQ and changes in CXCL13 expression levels for the diagnosis of lung tumors. A total of 60 patients with thoracic nodules and pleural effusion were included, with 30 of them having malignant pleural effusion (based on pathology) and the remaining 30 having benign thoracic nodules and pleural effusion. The relative expression level of CXCL13 was measured in the collected pleural effusions using Enzyme-Linked Immunosorbent Assay (ELISA). The relationship between CXCL13 expression levels and various clinical features was analyzed. A Receiver Operating Characteristic (ROC) curve analysis was conducted on the VTQ results and relative expression levels of CXCL13, and the areas under the curve, critical values, sensitivity, and specificity were calculated. Multivariate analysis incorporating multiple indicators was performed to determine the accuracy of lung tumor diagnosis. The results showed that the expression levels of CXCL13 and VTQ were significantly higher in the lung cancer group compared to the control group (P < 0.05). In the Non-Small Cell Lung Cancer (NSCLC) group, CXCL13 expression levels increased with later TNM staging and poorer tumor differentiation. The expression level of CXCL13 in adenocarcinoma was higher than that in squamous cell carcinoma. The ROC curve analysis revealed that CXCL13 had an area under the curve (AUC) of 0.74 (0.61, 0.86) with an optimal cut-off value of 777.82 pg/ml for diagnosing lung tumors. The ROC curve analysis of VTQ showed an AUC of 0.67 (0.53, 0.82) with a sensitivity of 60.0% and a specificity of 83.3%, and an optimal diagnostic cut-off of 3.33m/s. The combination of CXCL13 and VTQ for diagnosing thoracic tumors had an AUC of 0.842 (0.74, 0.94), which was significantly higher than either factor alone. The results of the study demonstrate the strong potential of combining VTQ results with chemokine CXCL13 expression levels for lung tumor diagnosis. Additionally, the findings suggest that elevated relative expression of CXCL13 in cases of malignant pleural effusion caused by non-small cell lung cancer may indicate a poor prognosis. This provides promising potential for using CXCL13 as a screening tool and prognostic indicator for patients with advanced lung cancer complicated by malignant pleural effusion.

FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2

Metastasis remains the major reason for the high mortality of patients with hepatocellular carcinoma (HCC). This study was designed to investigate the role of E-twenty-six-specific sequence variant 4 (ETV4) in promoting HCC metastasis and to explore a new combination therapy strategy for ETV4-mediated HCC metastasis. PLC/PRF/5, MHCC97H, Hepa1-6, and H22 cells were used to establish orthotopic HCC models. Clodronate liposomes were used to clear macrophages in C57BL/6 mice. Gr-1 monoclonal antibody was used to clear myeloid-derived suppressor cells (MDSCs) in C57BL/6 mice. Flow cytometry and immunofluorescence were used to detect the changes of key immune cells in the tumour microenvironment. ETV4 expression was positively related to higher tumour-node-metastasis (TNM) stage, poor tumour differentiation, microvascular invasion, and poor prognosis in human HCC. Overexpression of ETV4 in HCC cells transactivated PD-L1 and CCL2 expression, which increased tumour-associated macrophage (TAM) and MDSC infiltration and inhibited CD8+ T-cell accumulation. Knockdown of CCL2 by lentivirus or CCR2 inhibitor CCX872 treatment impaired ETV4-induced TAM and MDSC infiltration and HCC metastasis. Furthermore, FGF19/FGFR4 and HGF/c-MET jointly upregulated ETV4 expression through the ERK1/2 pathway. Additionally, ETV4 upregulated FGFR4 expression, and downregulation of FGFR4 decreased ETV4-enhanced HCC metastasis, which created a FGF19-ETV4-FGFR4 positive feedback loop. Finally, anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib prominently inhibited FGF19-ETV4 signalling-induced HCC metastasis. ETV4 is a prognostic biomarker, and anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib may be effective strategies to inhibit HCC metastasis. Here, we reported that ETV4 increased PD-L1 and chemokine CCL2 expression in HCC cells, which resulted in TAM and MDSC accumulation and CD8+ T-cell inhibition to facilitate HCC metastasis. More importantly, we found that anti-PD-L1 combined with FGFR4 inhibitor BLU-554 or MAPK inhibitor trametinib markedly inhibited FGF19-ETV4 signalling-mediated HCC metastasis. This preclinical study will provide a theoretical basis for the development of new combination immunotherapy strategies for patients with HCC.

CD8+ Cell Density Gradient across the Tumor Epithelium-Stromal Interface of Non-Muscle Invasive Papillary Urothelial Carcinoma Predicts Recurrence-Free Survival after BCG Immunotherapy.

Bacille Calmette-Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium-stroma interface of NMIPUC. Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium-stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface. By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (p < 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (p < 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492, p = 0.0063), poor differentiation (HR = 2.3672, p = 0.0457), and immunodrop (HR = 5.5072, p = 0.0455). We found that gradient indicators of CD8+ cell densities across the tumor epithelium-stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC.

FOXP3 and SQSTM1/P62 correlate with prognosis and immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common highly malignant tumours worldwide. FOXP3 and SQSTM1/P62 have been shown to be abnormally expressed in tumour cells, but their function in different tumours remains controversial. The present study was designed to evaluate the expression of FOXP3 and P62 in HCC and their prognostic value as well as their relationship with immune infiltration in HCC patients. The Gene Expression Omnibus (GEO) database and TNMplot.com platform were used to analyse the expression of FOXP3 and P62. The Cancer Genome Atlas (TCGA) database and Kaplan-Meier plotter were used to assess the impacts of FOXP3 and P62 on clinical prognosis. In addition, TCGA database was also used to examine the correlation between the expression of FOXP3 and P62 and tumour immune infiltration using the CIBERSORT algorithm. Finally, immunohistochemistry (IHC) was used to determine expression levels of FOXP3 and P62 in 89 HCC and adjacent normal liver tissues, and their effects on clinicopathological features and prognosis were verified. FOXP3 expression was downregulated in HCC tissues, while P62 expression was upregulated. FOXP3 underexpression and P62 overexpression were closely related to decreased overall survival (OS) in HCC patients. Additionally, the abnormal expression of FOXP3 and P62 was closely related to the infiltration levels of 12 types of immune cells, including regulatory T cells (Tregs), M2 macrophages, M0 macrophages, and CD8 T cells. Notably, in the validation model, abnormal FOXP3 and P62 expression was significantly associated with adverse clinicopathological factors in HCC patients, including elevated α-fetoprotein (AFP) levels, poor tumour differentiation, and increased Ki67 levels. Furthermore, low FOXP3 and high P62 expression were independent risk factors for predicting OS prognosis in HCC patients. FOXP3 and P62 have been shown to be important prognostic factors in HCC patients and are associated with immune cell infiltration in HCC. These findings suggest that FOXP3 and P62 may be valuable prognostic biomarkers and potential therapeutic targets for HCC treatment.

Investigation of the clinicopathological and prognostic role of circMTO1 in multiple cancers

ABSTRACT Objective To observe the prognostic value of circular RNA mitochondrial tRNA translation optimization 1 (circMTO1) in human tumors. Methods We searched multiple databases for related reports published before November 01, 2021. The OR/HR and 95% CI were extracted to explore the correlation between circMTO1 expression and clinicopathological features in various cancers. The stability of the results from meta-analysis was estimated via sensitivity analysis. We adopted Begg’s funnel plots and Egger’s test to appraise the potential bias of publication. Subgroup analysis for overall survival (OS) were also performed. Results 11 studies containing 1383 patients and 4 articles including 536 patients were enrolled. We found that low expression status of circMTO1 was significantly related to big tumor size (OR=2.11, 95% CI: 1.26-3.56, P<0.05), poor differentiation tumors (OR=2.09, 95% CI: 1.46-2.98, P<0.05), OS (HR=2.02, 95% CI: 1.63-2.50, P<0.05), disease-free survival (DFS) (HR=1.83, 95% CI: 1.27-2.56, P<0.05) of cancers. Subgroup analysis indicated that low expression status of circMTO1 was correlated with OS, regardless of analysis method, cut-off value, case number and NOS score. Conclusions The low expression of circMTO1 may predict big tumor size, poor differentiation and worse outcome of cancer, presenting that circMTO1 may be a useful biomarker for prognosis of tumors.

Utility of circulating tumor DNA (ctDNA) in the management of appendiceal adenocarcinoma (AA).

226 Background: Appendiceal adenocarcinoma (AA) is a rare and heterogenous cancer with marked differences in clinical course between high- and low-grade tumors. Unlike colorectal cancer (CRC) and other gastrointestinal malignancies, AA virtually never has hematogenous metastases, rather, metastasis is limited to the peritoneum. Here we present a retrospective, single institution study of AA to identify the prevalence of detectable ctDNA, evaluate the clinical predictive value of positive ctDNA, and assess what clinical, pathologic, or molecular features predict positive ctDNA. Methods: 160 blood samples from 147 patients with AA metastatic to the peritoneum were profiled with a CLIA approved 73 gene mutational panel as part of routine clinical practice. Paired tumor sequencing was available for 73 patients. Survival was measured starting from day ctDNA was drawn. Mutations that most likely represented clonal hematopoiesis were removed from analysis. Results: Out of 160 ctDNA samples, 120 were taken in the setting of radiographically apparent metastatic disease. Of these, 46 (38.3%) had any detectable mutation. 40 ctDNA tests were performed when patients had no radiographic evidence of disease (NED); 15 (37.5%) of which had any detectable mutation. High-grade tumors were more likely to have detectable ctDNA with detection rates of 10/46 (21.7%), 18/46 (39.1%), and 33/68 (48.5%) for well, moderately, and poorly-differentiated tumors, respectively. Restricting analysis to the 73 patients with paired tissue and blood samples and 73 genes sequenced in both, of 81 mutations detected in tumor only, 21 were detected in blood (sensitivity of 26%). Sensitivity was highest for mutation in TP53 (53.8%) suggesting these tumors may have a greater propensity to shed DNA into circulation. Overall, the sensitivity of ctDNA detection in metastatic AA was markedly less than what was observed in a cohort of 274 metastatic CRC patients from the same institution (288/581 = 49.6%). For AA patients with detectable ctDNA, variant allele frequency (VAF) in AA was significantly lower compared to CRC (median VAF 0.04% vs. 6%, p = &lt;0.0001). Detectable ctDNA was associated with shorter overall survival (46.2 mo for positive ctDNA vs. not-yet-reached for negative ctDNA, HR = 2.5, p = 0.016) and shorter disease free survival (DFS) (60 mo vs. not-yet-reached, HR = 3.4, p = 0.05). As expected, patients with radiographic evidence of disease did worse than patients with NED (HR = 2.1. p = 0.08), but of note this hazard ratio was less than that for positive ctDNA. Conclusions: In patients with AA, the presence of detectable ctDNA is associated with shorter overall and disease-free survival. Sensitivity of ctDNA detection in metastatic AA is overall markedly lower than CRC, with detection more likely in high-grade tumors and higher sensitivity in tumors containing TP53 mutation.

Immunohistochemical Study of Stathmin-1 as A Prognostic factor In Non-small cell lung carcinoma

Abstract &#x0D; &#x0D; Background&#x0D; Stathmin1 (also known as metablastin) is a major microtubule-depolymerizing protein that involved in cell cycle progression and cell motility.&#x0D; Stathmin1 has been found to be up-regulated in some cancers and correlated with cell differentiation and proliferation. &#x0D; Stathmin1 is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes in various cancers, including non-small cell lung cancer.&#x0D; &#x0D; Objective&#x0D; To evaluate the role of Immunohistochemical expression of stathmin1 in non-small lung carcinoma and its correlation to different prognostic factors or parameters.&#x0D; &#x0D; Materials and methods&#x0D; This retrospective study carried on formalin fixed paraffin embedded surgical specimens of lung tumors Applying the Immunohistochemical techniques by using the primary antibodies to stathmin1, statistical analysis done and assessment of correlation with different clinical and pathological parameters measured.&#x0D; &#x0D; Results &#x0D; Fifty cases of Non-small lung carcinomas that 42% adenocarcinoma,44% squamous cell carcinoma 10% adenosequamous and 4% non-small lung carcinoma 84 % were Stathmin-1 positive.&#x0D; No significant correlation between Stathmin-1 expression with age and gender of patients but Stathmin-1 expression were correlated with parameters including type and grade of tumor.&#x0D; High expression was noted in poorly differentiated tumors.&#x0D; &#x0D; Conclusions&#x0D; Measurement of stathmin1 level may be a beneficial prognostic biomarker for non-small lung tumors especially those of poorly differentiated tumors&#x0D; Stathmin1 expression in non-small cell lung carcinoma significantly correlated with poor tumor differentiation and could be considered as independent prognostic factor.

Accuracy of Endoscopic Biopsies for Determining Tumor Grade in Pre-resection Evaluation of Esophageal Adenocarcinoma

Background and AimsEndoscopic resection (ER) can be a curative treatment for early esophageal adenocarcinoma (EAC). Poor tumor differentiation is a histologic feature of noncurative ER and, when seen on preoperative biopsies, may lead to avoidance of endoscopic treatment. However, the accuracy of tumor grade on preoperative endoscopic biopsies remains unclear. The aim of this study was to determine the accuracy of tumor differentiation on endoscopic forceps biopsy compared with endoscopically or surgically resected tissue. MethodsThis retrospective cohort study from 2 tertiary referral centers compared tumor differentiation from preoperative biopsies with endoscopically or surgically resected EAC samples. Accuracy (%) of preoperative biopsy and agreement analyses (Gwet's AC2) were performed. ResultsIn total, 346 EAC lesions (225 esophagectomies, 121 ERs) were included. The overall accuracy and reliability of EAC grade on preoperative biopsies compared with postoperative tissue from ER or esophagectomy was 74% (114/154), with a substantial agreement coefficient (Gwet's AC2 0.78 [0.72-0.85]; P < 0.001). The accuracy of ER was only 56%, with moderate agreement (Gwet's AC2 0.60 [0.46-0.73]; P < 0.001). Poorly differentiated tumors were downgraded to moderately differentiated in 19.6% (20/102) of tumors, and conversely, moderately differentiated tumors were upgraded to poorly differentiated in 22.7% (37/163) of tumors. For patients with T1a tumors, poorly differentiated tumors on preoperative biopsies were downgraded to moderately differentiated tumors in 40% (4/10) of cases after resection. ConclusionsThe accuracy of tumor grade of EAC on preprocedural biopsies is suboptimal and should not be depended upon solely to make decisions regarding endoscopic treatment.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

Prognostic role of annexin A2 and cancer-associated fibroblasts in advanced non-small cell lung cancer: Implication in epithelial-mesenchymal transition and gefitinib resistance.

Despite advances in treatment of non-small cell lung cancer (NSCLC), its prognosis remains dismal. Development of drug resistance is a major obstacle against success of targeted epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors (TKI) therapy. This study aimed to assess the prognostic role of annexin A2 (ANXA2) expression, within both tumor cells and stroma, as well as cancer associated fibroblasts (CAFs) in NSCLC and to investigate their potential role in induction of epithelial mesenchymal transition (EMT) and resistance to gefitinib. Immunohistochemistry was performed to evaluate tumoral and stromal ANXA2 expression and α-SMA-stained CAFs in 110 advanced NSCLC patients. Furthermore, STAT3 and E-cadherin mRNA expression was studied by quantitative reverse transcription PCR (qRT-PCR). Both tumoral and stromal ANXA2 as well as CAFs were significantly related to clinical stage IV and malignant pleural effusion, while tumoral ANXA2 was significantly related to poor tumor differentiation. EGFR mutation and high tumoral ANXA2 were independent factors for poor overall survival, whereas high stromal and tumoral ANXA2 and high CAFs were independent predictors for poor progression-free survival. Moreover, high ANXA2 and CAFs were significantly associated with high STAT3 and low E-cadherin mRNA expression. Focusing on EGFR mutated cases, gefitinib resistance was significantly associated with high tumoral and stromal ANXA2, high CAFs, high STAT3 and low E-cadherin. CAFs and ANXA2 could be considered as poor prognostic parameters in advanced NSCLC and are potential factors for gefitinib therapy resistance through EMT induction.

Prognostic value of MSI2 expression in human malignancies: A PRISMA-compliant meta-analysis.

The prognostic value of Musashi-2 (MSI2) in human malignancies remains controversial. We thus conducted this meta-analysis to evaluate the association between MSI2 expression and prognosis of patients with malignancies. We searched EMBASE, PubMed and Web of Science up to June 2021 for eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the prognostic value of MSI2 expression. Odds ratios (ORs) with 95% CIs were calculated to evaluate the association between MSI2 expression and clinicopathological traits. Sixteen studies involving 2203 patients were finally included in this meta-analysis. We found that high MSI2 expression might predict unfavorable OS (HR = 1.85, 95% CI: 1.62-2.10, P < .0001) and DFS/RFS (HR = 2.19, 95% CI: 1.87-2.57, P < .0001). Besides, the pooled results indicated that increased MSI2 expression correlated with large tumor size, poor tumor differentiation, positive lymph node metastasis and advanced tumor stage. Taken together, our data implies that MSI2 overexpression is related to poor survival outcomes in patients with malignancy. Therefore, MSI2 may serve as a novel prognostic biomarker and therapeutic target of malignancies. However, large-scale prospective and homogeneous investigations should be conducted in the future to further validate our findings.

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC. Relevant studies were screened through PubMed, Web of Science, and other databases. The prognostic value of PC-associated circRNAs was assessed using the composite hazard ratio (HR), the diagnostic performance was assessed using the area under the summary receiver operator characteristic (SROC) curve (AUC), and the correlation with clinicopathological characteristics using the composite odds ratio (OR) was explored. In our study, 48 studies were included: 34 for prognosis, 11 for diagnosis, and 30 for correlation with clinicopathological characteristics. For prognosis, upregulated circRNAs were associated with poorer overall survival (OS) (HR = 2.02) and disease-free survival/progression-free survival (HR = 1.84) while downregulated circRNAs were associated with longer OS (HR = 0.55). Notably, the combination of circRNAs, including hsa_circ_0064288, hsa_circ_0000234, hsa_circ_0004680, hsa_circ_0071036, hsa_circ_0000677, and hsa_circ_0001460, was associated with worse OS (HR = 2.35). For diagnosis, the AUC was 0.83, and the pooled sensitivity and specificity were 0.79 and 0.73, respectively. For clinicopathologic characteristics, upregulated circRNAs were associated with poorer tumor differentiation, more nerve and vascular invasion, higher T stage, lymphatic metastasis, distant metastasis, advanced TNM stage, and higher preoperative CA19-9 level. In contrast, downregulated circRNAs were negatively associated with PC differentiation and lymphatic metastasis. Overall, our results showed that circRNAs are closely related to the prognosis and clinicopathological characteristics of PC patients and could be utilized for early diagnosis; thus, they are promising biomarkers for clinical application in PC.

Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma.

Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.