Tumor Node Metastasis Stage Research Articles

Preliminary Construction of Prognostic Risk Early Warning Model for Renal Cell Carcinoma with Type 2 Diabetes Mellitus Based on SMOTE Algorithm

157 patients with renal cell carcinoma who underwent surgical treatment in our hospital from January 2019 to December 2020 were selected as the study subjects. Patients were divided into good prognosis group and poor prognosis group according to whether there were end-point events (death or distant metastasis or recurrence of tumor) during the follow-up period. The clinical data of the two groups of patients were collected, the independent risk factors for poor prognosis were screened by univariate and binary logistic regression analysis and the logistic regression model (P1) were established. At the same time, the data set was improved based on synthetic minority oversampling technique algorithm and the early warning model (P2) of the improved data set was constructed and the prediction efficiency of the model was compared and verified. There were 27 patients with end-point events during the follow-up period. The increased course of type 2 diabetes mellitus, high preoperative haemoglobin A1C, high body mass index and tumor–node–metastasis stage T3/T4 were independent risk factors for poor prognosis in patients with type 2 diabetes mellitus and renal cell carcinoma (p<0.05), while metformin was an independent protective factor for poor prognosis (p<0.05). Early warning model based on synthetic minority oversampling technique, oversampling algorithm P2=1/[1+e-(-13.084-0.438*X1+0.446*X2+0.096*X3-0.781*X4+1.155*X5)], determination coefficient and receiver operating characteristic of P2 model, the areas under the curve were significantly higher than those of the P1 model. The course of type 2 diabetes mellitus, preoperative, body mass index level, tumor–node–metastasis stage and whether to receive metformin hypoglycemic therapy in patients with type 2 diabetes mellitus combined with renal cell carcinoma are closely related to poor prognosis. Based on this, the individualized early warning model established by synthetic minority oversampling technique oversampling algorithm is beneficial to patients with high risk of poor prognosis early identification.

Association between IL-6 and prognosis of gastric cancer: a retrospective study.

Gastric cancer (GC) is one of the common and fatal cancers. Even though the Tumor, Node, Metastasis (TNM) staging system is the most classical staging system recognized worldwide, it has been controversial because there are various factors affecting the prognosis of GC patients. The study aims to evaluate the relationship between interleukin-6 (IL-6) and several clinical indicators and construct a prognostic model to better predict the prognosis of GC. A retrospective study. Data of 249 patients with GC diagnosed in GC center of West China Hospital were collected. Clinicopathological characteristics were analyzed to determine whether there were differences between IL-6 HIGH group and IL-6 LOW group. Besides, the association between the two groups and tumor marker levels was clarified. The K-M curves of 3- and 5-year were plotted with log-rank test. Afterward, we conducted univariate and multivariate analysis and a predicting nomogram. Significantly, C-index, and calibration were used to evaluate the value of nomogram in predicting prognosis. The overall survival of GC in the IL-6 HIGH and IL-6 LOW groups were 47.8 months (95% CI: 42.1-53.4) and 57.9 months (95% CI: 54.1-61.7), respectively, with significant differences (p = 0.0046). Average tumor size of GC (p = 0.000) and nerve invasion (p = 0.018) were statistically significant between two groups. Multivariate analysis revealed that the factors affecting prognosis were IL-6 (<5.51 and ⩾5.51 pg/ml) (Hazard Ratio(HR): 1.665, 95% CI: 1.026-2.703, p = 0.039), N stage (HR: 1.336, 95% CI: 1.106-1.615, p = 0.003), and T stage (HR: 1.268, 95% CI: 0.998-1.611, p = 0.052), which were included in the nomogram with a C-index of 0.71. The current data calculated TNM staging C-index was 0.68, and the p-value for the difference between the two models was 0.08. Internal validation revealed that the predicted overall survival did not differ significantly from the actual observed patient survival. The differential expression of IL-6 has a tendency to differentiate the prognosis of GC patients. IL-6, N stage, and T stage are independent prognostic factors, and the new survival prognostic model consisting of the above three indicators is better than the classical TNM staging system. This study is a retrospective study, which does not require clinical registration.

Complication After Gastrectomy for Gastric Cancer According to Hospital Volume: Based on Korean Gastric Cancer Association-Led Nationwide Survey Data.

This study aimed to analyze the incidence and risk factors of complications following gastric cancer surgery in Korea and to compare the correlation between hospital complications based on the annual number of gastrectomies performed. A retrospective analysis was conducted using data from 12,244 patients from 64 Korean institutions. Complications were classified using the Clavien-Dindo classification (CDC). Univariate and multivariate analyses were performed to identify the risk factors for severe complications. Postoperative complications occurred in 14% of the patients, severe complications (CDC IIIa or higher) in 4.9%, and postoperative death in 0.2%. The study found that age, stage, American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group (ECOG) score, hospital stay, approach methods, and extent of gastric resection showed statistically significant differences depending on hospital volumes (P<0.05). In the univariate analysis, patient age, comorbidity, ASA score, ECOG score, approach methods, extent of gastric resection, tumor-node-metastasis (TNM) stage, and hospital volume were significant risk factors for severe complications. However, only age, sex, ASA score, ECOG score, extent of gastric resection, and TNM stage were statistically significant in the multivariate analysis (P<0.05). Hospital volume was not a significant risk factor in the multivariate analysis (P=0.152). Hospital volume was not a significant risk factor for complications after gastric cancer surgery. The differences in the frequencies of complications based on hospital volumes may be attributed to larger hospitals treating patients with younger age, lower ASA scores, better general conditions, and earlier TNM stages.

Hypermethylation-Mediated lncRNA MAGI2-AS3 Downregulation Facilitates Malignant Progression of Laryngeal Squamous Cell Carcinoma via Interacting With SPT6

Long noncoding RNAs (lncRNAs) have an effect on the occurrence and progression of a considerable number of diseases, especially cancer. Existing research has suggested that MAGI2 antisense RNA 3 (MAGI2-AS3) takes on a critical significance in the development of hepatocellular carcinoma and lung cancer. However, the functions of MAGI2-AS3 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In this study, MAGI2-AS3 expression level in LSCC tissue and cell lines was detected, and the effect of MAGI2-AS3 overexpressed on LSCC phenotypes and the possible influence mechanisms were examined. MAGI2-AS3 was downregulated in the tissues of LSCC patients versus non-tumor tissues, and it was correlated with advanced TNM (tumor, node, metastasis) stage and lymph node metastases, as indicated by the results of this study. MAGI2-AS3 inhibited the proliferation, migration, and invasion of LSCC cells in vitro and in vivo. Furthermore, the hypermethylation level of the MAGI2-AS3 promoter region was indicated by bisulfite genomic sequencing and methylation-specific polymerase chain reaction, such that MAGI2-AS3 expression was downregulated. Besides, MAGI2-AS3 promoter hypermethylation was regulated by DNA methyltransferase 1 (DNMT1), and MAGI2-AS3 expression was reversed by 5-Aza-2′-deoxycytidine (5-Aza). Moreover, the result of the RNA pull-down experiment suggested that 38 proteins were enriched in the MAGI2-AS3 group versus the control group in TU177 cells. To be specific, SPT6 (ie, a conserved protein) was enriched by fold change >10. SPT6 knockdown reduced the antitumor effect of MAGI2-AS3 in TU177 and AMC-HN-8 cells. Meanwhile, SPT6 overexpression inhibited the proliferation, metastasis, and invasion of TU177 and AMC-HN-8 cells. As revealed by the above findings, DNMT1-regulated MAGI2-AS3 promoter hypermethylation led to downregulated MAGI2-AS3 expression, such that the presence and progression of LSCC were inhibited in an SPT6 binding-dependent manner.

ZFPM2-AS1: An Oncogenic Long Non-coding RNA in Multiple Cancer Types.

Long non-coding RNA (lncRNA) is a novel kind of RNA transcript with lengths greater than 200 nucleotides. Functionally, lncRNAs lack the potential to encode peptides or proteins. Previous studies unveiled that lncRNA participated in numerous physiological and pathological processes, including cancer, aging, and immune responses. Newly discovered long noncoding RNA zinc finger protein, Friend of GATA (FOG) family member 2-antisense 1 (ZFPM2-AS1), located on the 8q23 chromosome, acts as a tumor stimulator in various cancer types, including Breast Cancer (BC), Colorectal Cancer (CRC), Esophageal Squamous Cell Carcinoma (ESCC), Gastric Cancer (GC), glioma, hepatocellular carcinoma (HCC), Lung Adenocarcinoma (LUAD), melanoma, non-small cell lung cancer (NSCLC), Retinoblastoma (RB), Small Cell Lung Cancer (SCLC) and thyroid cancer. Accumulative evidence also elucidated that ZFPM2-AS1 dysregulation was related to tumor proliferative, migratory, invasive, anti-apoptotic, and pro-epithelial-tomesenchymal Transition (EMT) effects, larger tumor volume, higher tumor weight, advanced tumor stage, high rates of lymphatic metastasis, distant metastasis, poor prognosis, histological differentiation, higher TNM (tumor, node, metastases) stage, depth of tumor invasion, reduced overall and disease- free survival, vein invasion, and shorter 5-year overall survival. Mechanistically, ZFPM2-AS1 acted as a ceRNA to play its oncogenic role. Thus, this study summarized the specific mechanisms of the lncRNA ZFPM2-AS1 in the aforementioned cancer types to reveal its novel application in cancer diagnosis, treatment, and prognosis.

Clinicopathological significance of cancer stem cell marker CD44/SOX2 in esophageal squamous cell carcinoma (ESCC) patients and construction of a nomogram to predict overall survival.

Esophageal squamous cell carcinoma (ESCC), a prevalent malignancy within the upper gastrointestinal system, is characterized by its unfavorable prognosis and the absence of specific indicators for outcome prediction and high-risk case identification. In our research, we examined the expression levels of cancer stem cells (CSCs), markers CD44/SOX2 in ESCC, scrutinized their association with clinicopathological parameters, and developed a predictive nomogram model. This model, which incorporates CD44/SOX2, aims to forecast the overall survival (OS) of patients afflicted with ESCC. Immunohistochemistry was utilized to detect the expression levels of CD44 and SOX2 in both cancerous and paracancerous tissues of 68 patients with ESCC. The correlation between CD44/SOX2 expression and clinicopathological parameters was subsequently analyzed. Factors impacting the prognosis of ESCC patients were assessed through univariate and multivariate Cox regression analyses. Leveraging the results of these multivariate regression analyses, a nomogram prognostic model was established to provide individualized predictions of ESCC patient survival outcomes. The predictive accuracy of the nomogram prognostic model was evaluated using the consistency index (C-index) and calibration curves. The expression levels of CD44 were markedly elevated in the tumor tissues of ESCC patients. Similarly, SOX2 was significantly overexpressed in the tumor tissues of ESCC patients. The positive expression of SOX2 in ESCC demonstrated a strong correlation with both the pathological T-stage and the presence of carcinoembryonic antigen. CD44 and SOX2 co-positive expression was significantly associated with the pathological T-stage and tumor node metastasis (TNM) stage. Furthermore, ESCC patients exhibiting CD44-positive expression in their tumor tissue generally had a more adverse prognosis. The co-expression of CD44 and SOX2 resulted in a grimmer prognosis compared to patients with other combinations. Multivariate Cox regression analysis identified the co-expression of CD44 and SOX2, the pathological T-stage, and lymph node metastasis as independent prognostic indicators for ESCC patients. The three identified variables were subsequently incorporated into a nomogram for predicting OS. The C-index of the measurement model and the area under the curve of the subjects' work characteristics showed good individual prediction. This prognostic model stratified patients into low- and high-risk categories. Analysis revealed that the 5-year OS rate was significantly higher in the low-risk group compared to the high-risk group. Elevated CD44 levels, indicative of CSC presence, are intimately linked with the oncogenesis of ESCC and are strongly predictive of unfavorable patient outcomes. Concurrently, the SOX2 gene exhibits a heightened expression in ESCC, markedly accelerating tumor progression and fostering more extensive disease infiltration. The co-expression of CD44 and SOX2 correlates significantly with ESCC patient prognosis, serving as a reliable, independent prognostic marker. Our constructed nomogram, incorporating CD44/SOX2 expression, enhances the prediction of OS and facilitates risk stratification in ESCC patients.

Involvement of long non-coding RNA LOXL1-AS1 in the tumourigenesis and development of malignant tumours: a narrative review.

Long noncoding RNAs (lncRNAs) are involved in a wide variety of physiological and pathological processes in organisms. LncRNAs play a significant role as oncogenic or tumour-suppressing factors in various biological processes associated with malignant tumours and are closely linked to the occurrence and development of malignancies. Lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) is a recently discovered lncRNA. It is upregulated in various malignant tumours and is associated with pathological characteristics such as tumour size, tumour node metastasis (TNM) staging, lymph node metastasis, and tumour prognosis. LOXL1-AS1 exerts its oncogenic role by competitively binding with multiple microRNAs (miRs), thereby regulating the expression of downstream target genes and controlling relevant signalling pathways. This article aims to explore the structure and the function of LOXL1-AS1, and the relationship between LOXL1-AS1 and the occurrence and development of human malignant tumours to provide a reference for further clinical research. English literature on LOXL1-AS1 in the occurrence and development of various malignant tumours was searched in PubMed. The main search terms were "LOXL1-AS1", "tumour". This article mainly summarizes the biological processes in which LOXL1-AS1 is involved in various human malignant tumours and the ways in which this lncRNA affects malignant biological behaviours such as proliferation, metastasis, invasion, and apoptosis of tumour cells through different molecular regulatory mechanisms. This article also explores the potential clinical significance and application prospects of LOXL1-AS1, aiming to provide a theoretical basis and reference for the clinical diagnosis, treatment, and screening of prognostic markers for malignant tumours. LOXL1-AS1 acts as a competing endogenous RNA (ceRNA), binding to miRs to regulate downstream target genes and exert its oncogenic effects. LOXL1-AS1 may become a novel molecular biomarker for cancer diagnosis and treatment in humans, and it may also serve as an independent prognostic indicator.

Somatic Super-Enhancer Epigenetic Signature for Overall Survival Prediction in Patients with Breast Invasive Carcinoma.

To analyze genome-wide super-enhancers (SEs) methylation signature of breast invasive carcinoma (BRCA) and its clinical value. Differential methylation sites (DMS) between BRCA and adjacent tissues from The Cancer Genome Atlas (TCGA) database were identified by using ChAMP package in R software. Super-enhancers were identified sing ROSE software. Overlap analysis was used to assess the potential DMS in SEs region. Feature selection was performed by Cox regression and least absolute shrinkage and selection operator (LASSO) algorithm based on TCGA training cohort. Prognosis model validation was performed in TCGA training cohort, TCGA validation cohort, and gene expression omnibus (GEO) test cohort. The gene ontology and KEGG analysis revealed that SEs target genes were significantly enriched in cell-migration-associated processes and pathways. A total of 83 654 DMS were identified between BRCA and adjacent tissues. Around 2397 DMS in SEs region were identified by overlap study and used to feature selection. By using Cox regression and LASSO algorithm, 42 features were selected to develop a clinical prediction model (CPM). Both training (TCGA) and validation cohorts (TCGA and GEO) show that the CPM has ideal discrimination and calibration. The CPM based on DMS at SE regions has ideal discrimination and calibration, which combined with tumor node metastasis (TNM) stage could improve prognostication, and thus contribute to individualized medicine.

PRR14 acts a novel oncogene activating the PI3K signal pathway in human cutaneous squamous cell carcinoma.

Proline rich protein 14 (PRR14) is considered as a new component of the nuclear fiber layer, it may be a key molecule in mediating nuclear morphological changes and functional changes in tumorigenesis. But, it's still unclear in human cutaneous squamous cell carcinoma (cSCC). In the study, the expression profiles of PRR14 in patients with cSCC were investigated by immunohistochemistry (IHC), also the PRR14 expression in cSCC tissues were detected using the methods of real-time quantitative PCR (RT-qPCR) and Western blot; cell counting kit-8 (CCK-8) assay, wound healing assay, matrigel-based transwell assay and Annexin V-FITC and PI double-staining with flow cytometry assay were used to investigate the biological functions of PRR14 in A431 and HSC-1 cSCC cells. Overexpression of PRR14 in cSCC patients was reported firstly in this study and its high expression was related to differentiation, thickness and tumor node metastasis (TNM) stage of cSCC. PRR14 inhibition with RNA interfering (RNAi) method resulted in the suppression of cell proliferation, migration and invasion but promotion the apoptosis of cSCC cells, and upregulation of the protein phosphorylation levels of mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K) and Akt. The study shows PRR14 maybe an activator of cSCC carcinogenesis through PI3K/Akt/mTOR signal pathway, and it also maybe a prognostic factor and new therapeutical target for cSCC treatment.

A Clinical Tool to Predict the Microvascular Invasion Risk in Patients with Hepatocellular Carcinoma.

Microvascular invasion (MVI) plays an important role in tumor progression. The aim of this study is to establish and validate an effective hematological nomogram for MVI prediction in hepatocellular carcinoma (HCC). A retrospective study was performed in a primary cohort that includes 1306 patients clinicopathologically diagnosed with HCC, and a validation cohort contained 563 continuous patients. Univariate logistic regression was used to assess the association between variables included both clinicopathologic factors and coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time [TT]) and MVI. Multiple logistic regression was used to construct a prediction nomogram. We tested the accuracy of the nomogram by discrimination and calibration, and then plotted decision curves to assess the benefits of the nomogram-assisted decisions in a clinical context. In the two cohorts, patients without MVI had the longest overall survival (OS), compared the OS with MVI. The multivariate analysis indicated that age, sex, tumor node metastasis (TNM) stage, aspartate aminotransferase, alpha fetoprotein, C-reactive protein, and TT were identified as significant independent predictors of MVI of HCC patients. The Hosmer-Lemeshow test showed good point estimate associated P value between predicted risk and observed risk across the deciles. Moreover, the calibration performance of the nomogram risk scores in each decile of the primary cohort was within 5 percentage points of the mean predicted risk score, and in the validation cohort, the observed risk in 90% decile was within 5 percentage points of the mean predicted risk score. A noninvasive and easy-to-use nomogram was established and may be used to predict preoperative MVI in HCC.

Ferroptosis and cuproptosis prognostic signature for prediction of prognosis, immunotherapy and drug sensitivity in hepatocellular carcinoma: development and validation based on TCGA and ICGC databases.

Hepatocellular carcinoma (HCC) is a common malignancy. Ferroptosis and cuproptosis promote HCC spread and proliferation. While fewer studies have combined ferroptosis and cuproptosis to construct prognostic signature of HCC. This work attempts to establish a novel scoring system for predicting HCC prognosis, immunotherapy, and medication sensitivity based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). FerrDb and previous literature were used to identify FRGs. CRGs came from original research. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases included the HCC transcriptional profile and clinical information [survival time, survival status, age, gender, Tumor Node Metastasis (TNM) stage, etc.]. Correlation, Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses were used to narrow down prognostic genes and develop an HCC risk model. Using "caret", R separated TCGA-HCC samples into a training risk set and an internal test risk set. As external validation, we used ICGC samples. We employed Kaplan-Meier analysis and receiver operating characteristic (ROC) curve to evaluate the model's clinical efficacy. CIBERSORT and TIMER measured immunocytic infiltration in high- and low-risk populations. TXNRD1 [hazard ratio (HR) =1.477, P<0.001], FTL (HR =1.373, P=0.001), GPX4 (HR =1.650, P=0.004), PRDX1 (HR =1.576, P=0.002), VDAC2 (HR =1.728, P=0.008), OTUB1 (HR =1.826, P=0.002), NRAS (HR =1.596, P=0.005), SLC38A1 (HR =1.290, P=0.002), and SLC1A5 (HR =1.306, P<0.001) were distinguished to build predictive model. In both the model cohort (P<0.001) and the validation cohort (P<0.05), low-risk patients had superior overall survival (OS). The areas under the curve (AUCs) of the ROC curves in the training cohort (1-, 3-, and 5-year AUCs: 0.751, 0.727, and 0.743), internal validation cohort (1-, 3-, and 5-year AUCs: 0.826, 0.624, and 0.589), and ICGC cohort (1-, 3-, and 5-year AUCs: 0.699, 0.702, and 0.568) were calculated. Infiltration of immune cells and immunological checkpoints were also connected with our signature. Treatments with BI.2536, Epothilone.B, Gemcitabine, Mitomycin.C, Obatoclax. Mesylate, and Sunitinib may profit high-risk patients. We analyzed FRGs and CRGs profiles in HCC and established a unique risk model for treatment and prognosis. Our data highlight FRGs and CRGs in clinical practice and suggest ferroptosis and cuproptosis may be therapeutic targets for HCC patients. To validate the model's clinical efficacy, more HCC cases and prospective clinical assessments are needed.

Characteristics and prognosis of young breast cancer patients with low expression of estrogen receptor

To evaluate the clinical characteristics and prognosis of young breast cancer patients with an ER of 1%–10%. Breast cancer patients aged ≤35 years old were selected and classified into three groups, ER-negative group, ER-low positive group (ER positivity: 1%–10%) and ER-high positive group (ER positivity: ≥10%), to compare their clinicopathological characteristics and prognosis. Of the 1387 patients assessed, 30.4% were ER-negative, 4.3% were ER-low positive, and 65.3% were ER-high positive. There was no difference in age, Tumor Node Metastasis (TNM) stage, histological type, adjuvant chemotherapy and adjuvant radiation therapy among the three groups (p &gt; 0.05). A higher histological grade and greater Human Epidermal Growth Factor Receptor-2 (HER-2) positivity were observed in the ER-low positive group than in the ER-high positive group (p &lt; 0.001). The number of patients with Progesterone Receptor (PR) negative in the ER-low positive group was between the other two groups. The recurrence rate of breast cancer in the ER-low positive group was 27.1%, which was similar to that of the ER-negative group (28%; p &gt; 0.05) but higher than the ER-high positive group (21.4%; p = 0.03). After a median follow-up of 74 months, the ER-high positive group had the longest Disease Free Survival (DFS) compared with the ER-negative group (p &lt; 0.0001) and ER-low positive group (p &lt; 0.05), while there was no significant difference in DFS between the latter two groups (p = 0.73). Similarly, the ER-high positive group had the longest Overall Survival (OS) than the ER-negative group (p &lt; 0.0001) and the ER-low positive group (p &lt; 0.05), while there was no statistical difference in OS between the latter two groups (p = 0.77). After endocrine therapy, no improvement in DFS (p = 0.71) and OS (p = 0.54) was observed in the ER-low positive group. In young breast cancer patients, the clinicopathological characteristics of the ER-low positive group were different from the ER-high positive group but were more similar to the ER-negative group. The DFS and OS were shorter than the ER-high group, and despite receiving endocrine therapy, DFS and OS of the ER-low positive group were not significantly prolonged.

Construction and validation of senescence risk score signature as a novel biomarker in liver hepatocellular carcinoma: a bioinformatic analysis.

Globally, liver cancer as one of the most frequent fatal malignancies, hits hard and fast. And the lack of effective treatments for liver hepatocellular carcinoma (LIHC), activates the researchers to promote promising precision medicine. Interestingly, emerging evidence proves that cellular senescence is involved in the progression of cancers and is recognized for its hallmark-promoting capabilities. Hence, efforts have been made to construct and validate the senescence risk score signature (SRSS) model as a novel prognostic biomarker for LIHC. The existing databases were mined for the following bioinformatics analyses. GSE22405, GSE57957, and senescence-related genes (SRGs) from public databases were utilized as a training set and the validation set was constituted by LIHC and pancreatic adenocarcinoma (PAAD) from The Cancer Genome Atlas (TCGA). After overlapping differentially expressed genes (DEGs) with SRGs, differentially expressed SRGs were identified with the progression of liver cancer through univariate and multivariate Cox regression and enrichment analyses. The model that utilized three SRGs was constructed using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Next, to evaluate the predictive performance of the SRSS model, the overall survival (OS) and survival rates were assessed through Kaplan-Meier (KM) and the receiver operating characteristic (ROC) curves. The predictive value for LIHC prognosis was further evaluated by capitalizing on risk score, nomograms, decision curve analysis (DCA) curves, and clinical information including tumor stages, gender, age, and race. DEGs were revealed as enriching in multiple tumor-related biological processes (BPs) and pathways. IGFBP3, SOCS2, and RACGAP1 were identified as the three considerable SRGs for the model. The high-risk group had a worse prognosis [both hazard ratio (HR) >1, P<0.001] and ROC curves showed a reliable predictive model with area under the curve (AUC) predictive values ranging from 0.673-0.816 for different-year survival rates respectively. The univariate and multivariate Cox regression analyses exhibited that risk score was the only credible prognostic predictor (HR >1, P<0.001) among clinical features such as tumor stage, age, etc., in LIHC. The nomograms, and DCA curves, combined with multiple clinical information, proved that the predictive ability of SRSS was strongest, followed by nomogram and traditional tumor node metastasis (TNM) stage was the weakest. In summary, comprehensive analyses supported that the SRSS model can better predict survival and risk in LIHC patients. Promisingly, it may point out a brand-new direction for LIHC therapy.

Лейкоцитоз и нетоз как маркеры неблагоприятного прогноза у онкогинекологических пациенток

The association between leukocytosis and poor disease prognosis has been reported in several types of cancer. However, to date, the potential mechanism of this predictive model has not been presented. Objective. To examine the correlation between the level of NETosis markers and white blood cell (WBC) count in the blood plasma of gynecologic oncology patients before treatment and the role of these indicators in predicting the course of disease. Patients and methods. This retrospective single-center non-randomized study included 212 patients hospitalized for surgical treatment and chemotherapy between 2016 and 2020: 58 with ovarian cancer, 44 with cervical cancer, 56 with breast cancer, and 54 with uterine cancer. Upon hospitalization, all patients had their WBC counts and other blood counts determined and recorded in a unified database. NETosis markers (citH3 and MPO:Ag concentrations) were determined in patients’ frozen plasma samples. Results. The WBC count of &gt;7·109/L before treatment was noted in patients with later stages of disease according to the TNM (tumor–node–metastasis) staging system. Patients with higher WBC counts had significantly higher MPO:Ag concentrations. The overall survival and progression-free survival rates were significantly worse in patients with WBC &gt;7·109/L and elevated concentrations of NETosis markers before treatment. Conclusion. The results obtained indicate that preoperative leukocytosis is associated with NETosis activation and is observed in patients with advanced stages of disease and poor prognosis. Key words: white blood cells, neutrophil extracellular traps, leukocytosis, NETosis, myeloperoxidase, citrullinated histone

Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer.

Gastric cancer is the fifth most common cancer worldwide. One of the chemotherapy agents, taxanes is important in increasing patients' survival. The purpose of this study is to assess the efficacy of taxane-based drugs versus non-taxanes in neoadjuvant chemotherapy in non-metastatic gastric adenocarcinoma (GA) in Iranian patients. In a historical cohort method, 65 patients between 18 and 75 years old who suffered from non-metastatic GA were included. Nineteen and 21 and 25 patients, had undergone DCF (docetaxel, cisplatin, 5fluorouracil) and FLOT (5fluorouracil, leucovorin, oxaliplatin, docetaxel) and FOLFOX6 (oxaliplatin, leucovorin, 5fluorouracil) regimens, respectively, between 2018 and 2021. Survival criteria consisting of progression-free survival (PFS), overall survival (OS), progression rate, and mortality rate were evaluated using the Kaplan-Meier method, in a three-year follow-up period. The majority of patients were male (72.3%), with a median age of 65 years. Most of the patients had lesions with tumor, node, metastasis (TNM) stage IIIb (27.7%) and poor differentiated pathological grade (49.2%). OS time had a significant correlation with the low TNM stage (P = 0.01), well-differentiated pathological grade (P = 0.005), and FLOT vs. FOLFOX protocol (20.3 vs. 12.2 months, respectively. P =0.04). FLOT regimen had significantly better OS survival vs. DCF regimen (20.3 vs. 15.4 months, respectively, P = 0.03). No significant correlation was observed between survival criteria and other factors like gender, age, past medical history, Karnofsky scale, and tumor location in the stomach. The taxane-based arm (sum of DSF and FLOT) had no superiority over the non-taxane arm in survival criteria. FLOT protocol, as a taxane-based regimen had better survival compared to FOLFOX protocol in neoadjuvant chemotherapy in gastric non-metastatic adenocarcinoma.

Assessment of Tumour Budding in Colorectal Carcinoma and its Correlation with Pathological Staging among Patients undergoing Resection at a Tertiary Care Hospital in Kerala, India

Introduction: Colorectal Carcinoma (CRC) is one of the most commonly diagnosed carcinomas and a significant cause of cancer-related deaths worldwide. The prognosis and treatment decisions rely on the Tumour, Node, Metastasis (TNM) Staging system. However, some tumours are classified as low-risk based on TNM stage exhibit adverse outcomes. Therefore, the search for additional prognostic factors is necessary. Tumour budding is an established independent prognostic factor, with high-grade tumour budding consistently linked to lymph node metastasis, local recurrence, and distant metastasis. Aim: To assess and grade tumour budding in CRC cases and examine its correlation with pathological staging. Materials and Methods: A cross-sectional study was conducted on 95 patients between December 2019 and December 2021 at Sree Gokulam Medical College and Research Foundation, Venjaramood, Trivandrum, India. Resected specimens from CRC patients were processed, and Haematoxylin and Eosin (H&amp;E) slides were examined for tumour budding assessment. Ten individual fields were scanned under a 10x objective to locate the hotspot area with the maximum number of tumour buds. Tumour buds were then counted under a 40x objective in the selected hotspot area. Tumour budding was categorised as low (0-1 bud), intermediate (2-4 buds), or high (5 or more buds). Immunohistochemistry (IHC) analysis with Pancytokeratin was carried out when assessment with H&amp;E slides alone was difficult. The correlation between tumour budding and pathological staging was evaluated, along with its association with various histopathological parameters. Results: The study included 95 patients, with a mean age of 68.22 years, comprising 58.95% males and 41.05% females. Low-grade tumour budding was observed in 42 (44.21%) cases, intermediate-grade budding in 34 (35.79%) cases, and highgrade tumour budding in 19 (20%) cases. There was a significant correlation between tumour budding and pathological staging (r-value=0.39) as well as the number of metastatic lymph nodes (r-value=0.34). The presence of lymph node metastasis and lymphovascular Invasion (LVI) showed a statistically significant association (p-value&lt;0.01). Conclusion: Tumour budding grading is a valuable histopathological finding, as it increases with higher T stage and presence of nodal metastasis, aiding in the prediction of nodal metastasis and recurrence. It is positively correlated with pathological staging and the number of metastatic lymph nodes. Including tumour budding grade in the histopathology report can assist clinicians in assessing prognosis and making treatment decisions.

The Value of Combined Detection of Serum PSA, MALAT1 and TMPRSS2-ETV1 in Evaluating the Progress and Prognosis of Prostate Cancer.

To explore the prognostic value of combined detection of serum prostate specific antigen (PSA), lung cancer metastasis-associated transcript 1 (MALAT1), transmembrane serine protease 2 (TMPRSS2), and erythropoietin-specific transforming gene variant 1 (ETV1) in prostate cancer. Ninety patients with prostate cancer who were treated in hospital were divided into two groups according to tumor node metastasis stage: Stage I-II group (n = 34) and stage III-IV group (n = 56). The serum levels of PSA, MALAT1, and TMPRSS2-ETV1 were detected in both groups and correlated with prostate cancer status to determine their value as indicators of disease progression and prognosis. Age, body mass index (BMI), and Gleason score differed significantly between the study group and the control group (p < 0.05). The expression levels of serum PSA and MALAT1 were higher in group III-IV than in group I-II, and the positive expression rate of TMPRSS2-ETV1 was significantly higher in group III-IV than in the control group (p < 0.05). Pearson's correlation analysis showed that serum PSA, MALAT1, and TMPRSS2-ETV1 were significantly correlated with prostate cancer (p < 0.05). Differences in PSA levels correlated with differences in age, BMI, type of pathology, and Gleason score, whereas differences in serum MALAT1 levels correlated with differences in age, BMI, and type of pathology. Gleason scores differed significantly between patients with positive and negative TMPRSS2-ETV1 indicators (p < 0.05). Multivariate logistic regression analysis showed that serum PSA, MALAT1, and TMPRSS2-ETV1 were independent risk factors affecting the prognosis of prostate cancer (p < 0.05). The areas under the curve (AUCs) of serum PSA, MALAT1, and TMPRSS2-ETV1 as prognostic predictors in prostate cancer were 0.692, 0.731, and 0.709, respectively, whereas the AUC of the combination was 0.819. Assessment of disease progression using the combination of indicators had a significantly higher prognostic value than single indicators (p < 0.05). Serum levels of PSA, MALAT1, and TMPRSS2-ETV1 were abnormal in patients with prostate cancer, and the combined detection of these factors provided a reference for assessing disease progression and predicting the prognosis of prostate cancer.

Small breast epithelial mucin as a useful prognostic marker for breast cancer patients.

This study aimed to evaluate the clinical utility of small breast epithelial mucin (SBEM) as a prognostic biomarker in an independent patient cohort. The paraffin-embedded tissues and clinicopathological data of 105 patients with breast cancer were collected, and the expression of SBEM in breast cancer samples was detected by immunohistochemical staining. The correlations between clinicopathological variables and the expression of SBEM were analyzed, and its significance as a prognostic indicator for breast cancer patients was determined. Immunohistochemical staining revealed that SBEM was expressed mostly in the cytomembrane and cytoplasm, with markedly increased SBEM expression (≥4 points on staining intensity) observed in 34 of 105 breast cancer tissues (32.4%). Elevated expression of SBEM was found to be significantly associated with larger tumor size (P = 0.002), more frequent lymph node metastasis (P = 0.029), advanced tumor node metastasis stage (P = 0.005), reduced expression of the progesterone receptor (PR) (P = 0.002), and a higher Ki-67 index (P = 0.006). Survival analysis indicated that patients with elevated SBEM expression had worse overall survival (OS) (5-year OS rate: 50.5 vs 93.9% for high and low SBEM expression, respectively, P < 0.001) and disease-free survival (DFS) (5-year DFS rate: 52.8 vs 81.7% for high and low SBEM expression, respectively, P = 0.001) rates than those with low expression of SBEM. Univariate and multivariate Cox analyses demonstrated that elevated expression of SBEM (hazard ratio [HR] = 1.994, 95% confidence interval [CI]: 1.008-3.945, P = 0.047), tumor size (HR = 2.318, 95% CI: 1.071-5.017, P = 0.033), and PR status (HR = 0.195, 95% CI: 0.055-0.694, P = 0.012) were independent predictors of OS in breast cancer patients. Elevated expression of SBEM was associated with both aggressive tumor characteristics and poor survival, indicating its potential as a useful prognostic biomarker for breast cancer patients.

Estimation of salivary and serum CYFRA 21-1 levels in patients with oral squamous cell carcinoma.

Cytokeratins are the largest sub-group of intermediate filaments and represent the most abundant proteins in epithelial cells. CYFRA 21-1 (human cytokeratin fragment antigen 21-1) is a soluble fragment of cytokeratin 19 known to increase in various malignancies. The present study is aimed to estimate salivary and serum levels of CYFRA 21-1 in oral squamous cell carcinoma (OSCC) patients and to compare them with healthy controls. A prospective, case-control study. This study included a total of 80 subjects, comprising 40 OSCC patients and 40 healthy controls. Saliva and blood samples were collected from the study population, and serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. The statistical tests applied were independent t-test, ANOVA test for comparison, and Post hoc test for correlation. A P value of < 0.05 was considered statistically significant. A statistically significant increase in salivary and serum CYFRA 21-1 levels was observed between OSCC and control groups and with an increase in the pathological tumour node metastasis stage and histopathological grade of OSCC. On correlating salivary and serum CYFRA 21-1 values, there were 3-fold higher salivary levels than serum. CYFRA 21-1 can be suggested as a tumour marker that can be used for the early diagnosis of the OSCC. Further prospective studies with a larger sample size and advanced techniques recommended before CYFRA 21-1 can be recommended for routine clinical use.

A study on histological grading systems of oral squamous cell carcinoma and comparison of their efficacy in determining the nature (clinical and histopathological) and prognosis of oral squamous cell carcinoma.

Tumour-Node-Metastasis (TNM) staging has been widely used for treatment planning and prognostication of oral cancers; however, TNM staging system alone is insufficient for optimal prognostication. A combined assessment of clinical staging and cytomorphology might serve as a more specific measure for prognostication. The present study attempted to compare the efficacy of histologic grading systems (Jakobbson et al., Anneroth et al. and Bryne et al.) of malignancy in determining the nature and prognosis of oral squamous cell carcinoma (OSCC). Tumour protein (TP53) immunohistochemical marker was used to determine the aggressiveness of OSCC. Tissue sections from 24 biopsy-proven cases of OSCC were stained with anti-TP53 antibody. Hundred cells in each case were counted and tabulated. Cases were graded using three histopathological grading systems. Findings were compared and correlated with TP53 immunopositivity and clinical parameters. Positive correlation was observed between TP53 immunostaining and grading scores of each system. Highest correlation was observed with Jakobbson et al. grading system (r2 value = 0.91, P < 0.001). Significant results were observed on comparing grades of Jakobsson et al., Anneroth et al. and Bryne et al. grading system with segregated groups of TP53 immunopositive cases (P = 0.004, P = 0.003, P = 0.001, respectively). No significant results were observed on comparing grades of histopathological systems with clinical parameters. Both, clinical and histopathological grading systems, with immunohistochemistry, should be taken into account during the assessment of OSCC, for treatment planning and better prediction of tumour prognosis.