Identification of prognostic biomarkers associated with tumor microenvironment in ceRNA network for esophageal squamous cell carcinoma: a bioinformatics study based on TCGA database

Background Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in the world with high incidence rate and poor prognosis. Infiltrated immune and stromal cells are vital components of tumor microenvironment (TME) and have a significant impact on the progression of ESCC. The competitive endogenous RNA (ceRNA) hypothesis has been proved important in the molecular biological mechanisms of tumor development. However, there are few studies on the relationship between ceRNA and ESCC TME. Methods The proportion of tumor-infiltrating immune cells and the amount of stromal and immune cells in ESCC cases were calculated from The Cancer Genome Atlas database using the CIBERSORT and ESTIMATE calculation methods. After stratified identification of differentially expressed genes, WGCNA and miRNA prediction system were applied to construct ceRNA network. Finally, PPI network and survival analysis were selected to discriminate prognostic signature. And the results were verified in two independent groups from Gene Expression Omnibus and Lanzhou, China. Results We found that high Stromal and ESTIMATE scores were significantly associated with poor overall survival. Three TME-related key prognostic genes were screened, namely, LCP2, CD86, SLA. And the expression of them was significantly correlated with infiltrated immunocytes. It is also found that ESTIMATE Score and the expression of CD86 were both related to TNM system of ESCC. Conclusions We identified three novel TME-related prognostic markers and their lncRNA-miRNA-mRNA pathway in ESCC patients, which may provide new strategies for the targeted therapy.

Prognostic Nomogram for Liver Metastatic Colon Cancer Based on Histological Type, Tumor Differentiation, and Tumor Deposit: A TRIPOD Compliant Large-Scale Survival Study

ObjectiveA proportional hazard model was applied to develop a large-scale prognostic model and nomogram incorporating clinicopathological characteristics, histological type, tumor differentiation grade, and tumor deposit count to provide clinicians and patients diagnosed with colon cancer liver metastases (CLM) a more comprehensive and practical outcome measure.MethodsUsing the Transparent Reporting of multivariable prediction models for individual Prognosis or Diagnosis (TRIPOD) guidelines, this study identified 14,697 patients diagnosed with CLM from 1975 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) 21 registry database. Patients were divided into a modeling group (n=9800), an internal validation group (n=4897) using computerized randomization. An independent external validation cohort (n=60) was obtained. Univariable and multivariate Cox analyses were performed to identify prognostic predictors for overall survival (OS). Subsequently, the nomogram was constructed, and the verification was undertaken by receiver operating curves (AUC) and calibration curves.ResultsHistological type, tumor differentiation grade, and tumor deposit count were independent prognostic predictors for CLM. The nomogram consisted of age, sex, primary site, T category, N category, metastasis of bone, brain or lung, surgery, and chemotherapy. The model achieved excellent prediction power on both internal (mean AUC=0.811) and external validation (mean AUC=0.727), respectively, which were significantly higher than the American Joint Committee on Cancer (AJCC) TNM system.ConclusionThis study proposes a prognostic nomogram for predicting 1- and 2-year survival based on histopathological and population-based data of CLM patients developed using TRIPOD guidelines. Compared with the TNM stage, our nomogram has better consistency and calibration for predicting the OS of CLM patients.

PET/CT in the Staging of Non-Small Cell Lung Cancer

Background NSCLC accounts for about 80% of all lung cancers. The current criteria for its staging is based on the TNM system that determines treatment options and predicts survival rate in patients. Objective To evaluate the diagnostic accuracy of 18F-FDG PET/CT in staging of NSCLC patients Methods A prospective study, conducted at Ain Shams University hospitals on pathologically proven patients of NSCLC, the patients were investigated using CT and PET/CT in the period between October 2018 till end of June 2019. Results A total of 40 patients were evaluated with the age ranging from 37 to 77 years old, whether the mean was 55.63 years (SD ± 10.29). There were 31 male cases and 9 female cases. When we compared CECT against PET-CT for staging, PET-CT helped upstage disease in 10 of 40 patients (25%) and downstage in 3 of 40 patients (7.5%). Conclusion PET/CT is a useful imaging tool in initial staging of the newely diagnosed patients with NSCLC. It is better thаn СT alone for detection of malignant lesions for accurate staging. It can change the strategy of treatment according to its findings

Pedicled transverse rectus abdominis myocutaneous flap breast reconstruction: Hospital Kuala Lumpur’s early experience

Background: Breast reconstruction is traditionally performed by the plastic surgeons. In the last four years, we have embarked on autologous breast reconstruction. We conducted a retrospective study to evaluate the complications and cosmetic outcomes of a pedicled transverse rectus abdominis myo-cutaneous (TRAM) flap breast reconstruction.Methods: We enrolled forty-one patients who underwent a TRAM flap reconstructive surgery between January 2016 and January 2020 at the hospital Kuala Lumpur, Malaysia. Thorough retrospective reviews of medical records were performed. Patient’s satisfaction on the cosmetic outcome were assessed with the breast-Q questionnaire.Results: Forty-one patients with a mean age of forty-six years old, had ipsilateral pedicled TRAM breast reconstructions for various breast pathologies including invasive carcinoma (n=31, 75.6%), ductal carcinoma in situ (n=8, 19.5%) and phylloides tumor (n=2, 4.9%). Immediate reconstruction was performed in thirty-nine patients and delayed reconstruction in two patients. Based on The American joint committee on cancer (AJCC) TNM system, the pathologic stages among those patients with breast cancer were 0 (n=8, 20.5%), I (n=3, 7.69%), II (n=9, 23.1%), III (n=18, 46.1%), and IV (n=1, 2.56%). During the mean follow-up of seventeen months, flap and donor site complications were reported in twelve patients (29.3%) and five patients (12.1%) respectively. Nineteen were very satisfied and sixteen were satisfied.Conclusions: Breast reconstruction with a TRAM flap can be safely performed by the oncoplastic breast surgeons with good aesthetic outcomes.

Prognostic significance of the TNM system criteria, levels of serum insulin-like growth factors and their transport proteins, VEGF and MMP-7 in colorectal cancer

The analysis of long-term results of treatment of 88 primary patients with colon adenocarcinoma at various stages of tumor process is presented, taking into account the TNM system criteria, and serum IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, VEGF, and MMP-7 levels. The overall survival rate assessed by Kaplan-Meier method and Cox multivariate regression model was used as the criterion of prognosis. It was established that IGF-1, IGFBP-2 and VEGF serum levels along with the stage of colorectal cancer might be considered as statistically significant independent predictors of overall survival in patients.

Is Tumor Budding a New Predictor for Early Cystectomy in pT1 High-Grade Bladder Cancer?

<b><i>Background &amp; Objectives:</i></b> We aimed to evaluate the risk of progression in high-grade T1 (HGT1) tumors using tumor budding (TB) and other standard clinical and histological features. TB is defined as an isolated cancer cell or a cluster composed of fewer than 5 cells scattered in the stroma and is usually used as a strong predictor of lymph node metastasis in T1 colorectal cancer. <b><i>Methods:</i></b> This is an observational longitudinal cohort study involving 168 consecutive patients with HGT1 between 2013 and 2016. Cox regression was performed to analyze the relationship between the clinical and histological features and progression. All slides were blindly assessed by 2 genitourinary pathologists. Budding was determined to be positive when the number of buds was equal to or greater than 6. <b><i>Results:</i></b> The median age was 75 years; 152 (90.5%) patients were men, and 49 (29.2%) were positive for TB. At a median follow-up time of 35 months, 33 patients (19.6%) showed progression. Progression was observed in 32.7% of the patients positive for TB and in only 14.3% of those who were negative (<i>p</i> = 0.006). TB was significantly associated with the endoscopic tumor pattern (TP) (papillary/solid) and lymphovascular invasion (LVI). Univariate analysis showed that TB, carcinoma in situ (CIS), TP, LVI, sub-staging, and BCG induction predict progression. The multivariate analysis showed that TB (<i>p</i> = 0.032, hazard ratio 2.1), CIS, TP, and lack of BCG induction were significant for progression. <b><i>Conclusions:</i></b> TB is a new and significant pathological variable for predicting progression in HGT1 tumors and can be easily introduced in clinical practice. Its inclusion in the TNM system should be carefully considered, as it may aid early cystectomy decisions.

MODERN METHODS OF DIAGNOSIS OF MAMMARY TUMOR AND TUMOR-LIKE LESIONS IN CATS

The paper provides an overview of the classification and diagnosis of feline mammary tumors (FMT) in cats. The clinical stage of neoplastic process is one of the driving prognostic factors. In accordance with the WHO recommendations 1980, it is determined by the TNM system: the size of neoplasm, the state of regional lymph nodes and the presence/absence of distant metastases. The clinical stage of the disease is defined based on the obtained data during the examination, surgery and study of the postoperative material (excised tumor, the edges of the resection and regional lymph nodes). It was found that tumors larger than 3 cm have a significantly worse prognosis than tumors smaller than 3 cm. The median survival with a tumor size of less than 3 cm is 1.75 times greater (21 months versus 12 months) than with a tumor size of more than 3 cm. The most significant morphological prognostic factor is the histological type of malignant tumor and the histological gradation of tumor tissue. Among carcinomas, the most invasive are micropapillary, solid and cribriform carcinomas, the most unaggressive is carcinoma in situ. Adverse prognostic factors of mammary cancer in cats are a high Ki67 index of proliferative activity, hyperexpression of Her-2 epidermal growth factor, cyclooxygenase-2, absence or low level of expression of receptors to estrogen and/or progesterone by tumor cells (less than 10%), as well as a high level of expression by tumor cells of VEGF (vascular endothelial growth factor).

Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in papillary renal cell carcinoma patients after receiving curative surgery based on a retrospective cohort

Background Inflammatory response biomarkers have been studied as promising prognostic factors in renal cell carcinoma, but few studies have focused on papillary renal cell carcinoma (PRCC). This study was performed to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in PRCC patients. Methods In total, 122 postoperative PRCC patients selected from 366 non-clear cell renal cell carcinoma patients were enrolled from our institution between 2012 and 2020. The optimal cutoff value of the NLR was assessed by receiver operating characteristic (ROC) curve analysis, and the Kaplan–Meier method and Cox's proportional hazards regression models were performed to analyze the association of the NLR with overall survival (OS). In addition, the potential of tumor-node-metastasis (TNM) stage, the NLR and an NLR-TNM system to predict survival were compared with ROC curves, and clinical usefulness of the predicting models were assessed by decision curve analysis. Results A threshold value of 2.39 for the NLR for OS analysis was determined by ROC curve analysis. An NLR ≥ 2.39 was associated with a more advanced TNM stage (P < 0.01) and larger tumors (P < 0.05) than a low NLR, as well as pathological subtype II (P < 0.05), and the patients with a high NLR also exhibited significantly worse overall survival outcomes (P < 0.05). The NLR was determined to be a significant independent prognostic indicator by univariable and multivariable analyses (HR = 5.56, P < 0.05). Furthermore, TNM stage and the NLR were integrated, and the area under the curve (AUC) of for the NLR-TNM system was larger than that of for the TNM system when predicting overall survival (0.84 vs 0.73, P = 0.04). Decision curve analysis also demonstrated a better clinical value for the NLR-TNM model to predict the prognosis. Conclusion A high preoperative NLR was associated with poor clinical and pathologic parameters in patients with PRCC; moreover, the NLR was also an independent prognostic factor for the OS of patients with PRCC. The NLR-TNM system, which was a model that integrated the NLR with TNM staging, could improve the ability to predict overall survival.

Therapeutic Implications of the Immunoscore in Patients with Colorectal Cancer

Four decades were needed to progress from the first demonstration of the independent prognostic value of lymphocytes infiltration in rectal cancers to the first recommendation from the international guidelines for the use of a standardized immune assay, namely the “Immunoscore” (IS), to accurately prognosticate colon cancers beyond the TNM-system. The standardization process included not only the IS conceptualization, development, fine-tuning, and validation by a large international consortium, but also a demonstration of the robustness and reproducibility across the world and testing of international norms and their effects on the IS. This is the first step of a major change of paradigm that now perceives cancer as the result of contradicting driving forces, i.e., the tumor expansion and the immune response, interacting dynamically and influencing the prognosis and the response to therapies. This prompted us to evaluate and evidence the capacity of the tumor immune status, as reflected by the IS, to accurately predict chemotherapy responses in an international, randomized cohort study of colon cancer. Moreover, we developed a derived IS performed on initial diagnostic biopsies (ISB) to assess response levels to neoadjuvant therapies. In rectal cancer, ISB was positively correlated with the degree of histologic response to neoadjuvant chemoradiotherapy and identified - alone and even more accurately if combined with clinical data- patients eligible for a noninvasive strategy. Based on these results, we are currently setting up an international cohort for confirmation. The potential role of IS with immunotherapies must be anticipated.