Tumor Node Metastasis Stage Research Articles

Intelligent prognosis evaluation system for stage I-III resected non-small-cell lung cancer patients on CT images: a multi-center study

Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744-0.846), internal validation set (0.783; 95% CI: 0.744-0.825) and external validation set (0.817; 95% CI: 0.786-0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p<0.05 for all). The IPES provided a non-invasive way to obtain prognosis-related information from patients. The identification of IPES for resected NSCLC patients with low and high prognostic risk in the same TNM stage or with the same EGFR genotype suggests that IPES have potential to offer more personalized treatment and surveillance suggestion for NSCLC patients. This study was funded by the National Natural Science Foundation of China (grant 62272055, 92259303, 92059203), New Cornerstone Science Foundation through the XPLORER PRIZE, Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (K.C.), Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), BUPT Excellent Ph.D. Students Foundation (CX2022104).

EXOSC2 Mediates the Pro-tumor Role of WTAP in Breast Cancer Cells via Activating the Wnt/β-Catenin Signal.

BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/β-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3'-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/β-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/β-catenin signal.

The Use of Metformin and Postoperative Insulin Pump Were Predictive Factors for Outcomes of Diabetic Colorectal Cancer Patients after Surgery

Purpose This present study aims to explore the influence of metformin and postoperative insulin pump use on colorectal cancer (CRC) patients with type II diabetes mellitus (T2DM) who received surgery in terms of short-term and long-term outcomes. Methods 613 CRC patients who had comorbid T2DM and received surgery at a single clinical center from Jan, 2011 to Dec, 2021 were included in this study. Univariate and multivariate logistic regression analyses were used to find predictive factors for overall complications and major complications. Cox regression analyses was used to find prognostic factors for overall survival (OS) and disease-free survival (DFS). All statistical analysis was performed using SPSS (version 22.0) software. The Kaplan-Meier curve was used to show the OS and DFS between the insulin pump group and the no insulin pump group. Results Multivariate logistic regression analysis reported that lower body mass index (BMI) (p < 0.01, OR = 0.922, 95% CI = 0.870-0.977) and metformin use (p = 0.03, OR = 0.643, 95% CI = 0.431-0.959) were independent protective factors for overall complications, and insulin pump after surgery (p < 0.01, OR = 3.991, 95% CI = 2.434-6.544) was an independent risk factor for overall complications. As for major complications, metformin use (p = 0.042, OR = 0.274, 95% CI = 0.079-0.956) and insulin pump after surgery (p = 0.03, OR = 2.892, 95% CI = 1.107-7.552) remained independent protective factors and independent risk factors, respectively. Moreover, in Cox regression analyses, age (OS: p < 0.01, HR = 1.032, 95% CI = 1.008-1.057; DFS: p < 0.01, HR = 1.030, 95% CI = 1.008-1.052), tumor stage (OS: p < 0.01, HR = 1.709, 95% CI = 1.244-2.346; DFS: p < 0.01, HR = 1.696, 95% CI = 1.276-2.254), and Insulin pump after surgery (OS: p < 0.01, HR = 2.923, 95% CI = 1.887-4.527; DFS: p < 0.01, HR = 2.671, 95% CI = 1.779-4.009) were independent prognostic factors for both OS and DFS. After comparing the OS and DFS between the insulin pump group and the no insulin pump group, patients who received postoperative insulin pump had worse OS and DFS in all tumor node metastasis (TNM) stages (p < 0.01). Conclusion Diabetic CRC patients who used metformin had a lower risk of postoperative complications. However, there was no difference from patients not using metformin in terms of survival. Furthermore, patients receiving postoperative insulin pump had more postoperative complications and worse survival in all TNM stages.

CXCL5 and CXCL14, but not CXCL16 as potential biomarkers of colorectal cancer

Experts emphasize that colorectal cancer (CRC) incidence and mortality are increasing. That is why its early detection is of the utmost importance. Patients with cancer diagnosed in earlier stages have a better prognosis and a chance for faster implementation of treatment. Consequently, it is vital to search for new parameters that could be useful in its diagnosis. Therefore, we evaluated the usefulness of CXCL5, CXCL14 and CXCL16 in serum of 115 participants (75 CRC patients and 40 healthy volunteers). Concentrations of all parameters were measured using Luminex. CRP (C-reactive protein) levels were determined by immunoturbidimetry, while levels of classical tumor markers were measured using CMIA (Chemiluminescence Microparticle Immunoassay). Concentrations of CXCL5 were statistically higher in the CRC group when compared to healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of CXCL5 and CXCL14 were higher than those of CA 19–9. Obtained results suggest the usefulness of CXCL5 and CXCL16 in the determination of distant metastases and differentiation between TNM (Tumor-Node-Metastasis) stages, as well as the usefulness of CXCL14 and CRP combination in CRC detection (primary or recurrence). However, further studies concerning their role in CRC progression are crucial to confirm and explain their diagnostic utility and clinical application as biomarkers.

Decoding tumor stage by peritumoral and intratumoral radiomics in resectable esophageal squamous cell carcinoma

PurposeTo evaluate the potential application of radiomics in predicting Tumor-Node-Metastasis (TNM) stage in patients with resectable esophageal squamous cell carcinoma (ESCC).MethodsThis retrospective study included 122 consecutive patients (mean age, 57 years; 27 women). Corresponding tumor of interest was identified on axial arterial-phase CT images with manual annotation. Radiomics features were extracted from intra- and peritumoral regions. Features were pruned to train LASSO regression model with 93 patients to construct a radiomics signature, whose performance was validated in a test set of 29 patients. Prognostic value of radiomics-predicted TNM stage was estimated by survival analysis in the entire cohort.ResultsThe radiomics signature incorporating one intratumoral and four peritumoral features was significantly associated with TNM stage. This signature discriminated tumor stage with an area under curve (AUC) of 0.823 in the training set, with similar performance in the test set (AUC 0.813). Recurrence-free survival (RFS) was significantly different between different radiomics-predicted TNM stage groups (Low-risk vs high-risk, log-rank P = 0.004). Univariate and multivariate Cox regression analyses revealed that radiomics-predicted TNM stage was an independent preoperative factor for RFS.ConclusionsThe proposed radiomics signature combing intratumoral and peritumoral features was predictive of TNM stage and associated with prognostication in ESCC.Graphical abstract

Red blood cell distribution width has a prognostic value for gastric cancer patients after gastrectomy: A pooling-up analysis.

Our study aims to investigate whether preoperative red blood cell distribution width (RDW) has a prognostic value for patients after gastric cancer (GC) surgery. We searched articles in 3 databases including PubMed, Embase, and the Cochrane Library on May 16th, 2022. The prognostic indicators included overall survival (OS) and disease-free survival (DFS). RevMan 5.3 (The Cochrane Collaboration, London, United Kingdom) and Stata V16.0 were used for statistical analysis. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used to assess risk of bias of the included studies. Ten articles involving 2740 patients were included. RDW was a prognostic factor for OS (hazard ratio = 1.81, 95% confidence interval [CI] = 1.38-2.37, P < .01) and DFS (hazard ratio = 1.99, I2 = 26%, 95% CI = 1.53-2.58, P < .01) for GC patients. Meanwhile, there were some differences between the high RDW group and the low RDW group. We found more patients older than 60 years old (OR = 2.58, 95% CI = 1.08-6.13, P = .03), larger tumor diameter (OR = 1.95, 95% CI = 1.33-2.85, P < .01) and later T stage (OR = 1.91, 95% CI = 1.07-3.42, P = .03) in the high RDW group than the low RDW group. No statistic difference was found in gender, N stage, tumor node metastasis stage, vascular invasion, differentiation, and adjuvant therapy between the 2 groups (P > .05). RDW was an independent prognostic factor for both OS and DFS of GC patients. High RDW level were strongly associated with poor survival.

Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma

The objective of this study was to investigate the clinical significance and roles of tumor progression locus 2 (TPL2) and peptidyl-prolyl cis–trans isomerase 1 (Pin1) in the occurrence and development of breast invasive ductal carcinoma (IDC). Immunohistochemistry was used to detect the expression of TPL2 and Pin1 in human breast tissues, which included normal breast tissues (Normal), tissues with fibrocystic changes (FCC), ductal carcinoma in situ (DCIS), and IDC. The roles of TPL2 and Pin1 in the occurrence and development of IDC, as well as the correlation between their expression levels and clinicopathological parameters, were analyzed. Compared with Normal and FCC groups, the overexpression of TPL2 and Pin1 was significantly increased in DCIS and IDC groups (DCIS vs Normal: P = 0.002/P < 0.001; IDC vs Normal: P = 0.007/P = 0.003; DCIS vs. FCC: P = 0.008/P = 0.004; IDC vs. FCC: P = 0.04/P = 0.043). The expression levels of TPL2 and Pin1 were positively correlated in DCIS and IDC groups (P = 0.001, P = 0.011). In the IDC group, the Ki67 level in the TPL2 overexpression group was significantly lower than that in the TPL2 low expression group (P = 0.02). The TPL2 overexpression rate was significantly higher in IDC with histological grades 1–2 than that in IDC with histological grade 3 (P = 0.029). The TPL2 overexpression rate in IDC with tumor-node-metastasis (TNM) stage I was significantly higher than that in IDC with TNM stages II–III (P = 0.035). We conclude that TPL2 and Pin1 may synergistically promote the occurrence and development of IDC, but TPL2 overexpression may be an early molecular event in IDC development. TPL2 overexpression is significantly related with IDC with lower malignancy or earlier TNM stage, suggesting that the prognosis of IDC patients with TPL2 overexpression may be better and TPL2 overexpression may be a predictor of good prognosis in IDC.

Risk factors influencing chemotherapy compliance and survival of elderly patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has high degree of malignance and proneness to recurrence and metastasis. The aim of this study was to analyse the risk factors influencing the chemotherapy compliance and survival status of elderly NSCLC patients. The clinical data of 110 patients admitted from January 2014 to March 2018 were retrospectively analysed. They were assigned to non-chemotherapy (n=25), partial chemotherapy (n=30) and complete chemotherapy (n=55) groups according to chemotherapy compliance, and followed up until March 2021. Their clinicopathological characteristics were investigated by univariate analysis and then multivariate Cox regression analysis. The survival rates were compared by Kaplan-Meier survival curve and log-rank test. Among the 110 NSCLC patients, 25 did not receive chemotherapy, 30 underwent partial chemotherapy and 55 received complete chemotherapy. Educational level, pathological tumor-node-metastasis (TNM) stage, pathological type, surgical approach, place of residence, payment mode and chemotherapy stage were independent risk factors influencing the chemotherapy compliance (P<0.05). Particular attention should be paid to improving the chemotherapy compliance of patients with low educational level, late TNM stage, medical history of squamous cell carcinoma, history of thoracotomy, living in rural areas and no medical insurance, and those in the recurrence period or consolidation period of chemotherapy.

Development of a Survival Nomogram for Esophageal Squamous Cell Carcinoma Patients: a Population-Based Analysis.

In this study, we developed a prognostic nomogram for esophageal squamous cell carcinoma (ESCC) patients. Patients diagnosed with ESCC from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2017) and a local hospital were enrolled in this retrospective cohort study. Prognoses were analyzed using the R language software, and the predictive power of the model was then assessed by the Harrell concordance index (C-index) and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. In total, 2915 ESCC patients from SEER database were divided into training and validation cohorts. Multivariate analysis revealed that sex, marital status, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation all showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (also with tumor grade). These characteristics were employed to build a nomogram. The C-index of the nomogram for OS and CSS prediction was 0.743 and 0.748 for the training cohort, which were superior to the predictive power of the 7th TNM staging system. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.805 and 0.812, respectively, and the AUCs for CSS were 0.811 and 0.821, respectively. ROC and calibration curves of data from the SEER internal validation set and of data from our hospital showed that this model had good accuracy for predicting the prognosis of ESCC patient. The nomogram developed in this study provides a useful tool for accurately estimating OS and CSS for ESCC patients.

Application of preoperative serum CYFRA 21-1 level in the prognosis of colorectal cancer

To explore the predictive value of preoperative serum CYFRA 21-1 in colorectal cancer (CRC) resection patients. In this retrospective study, 456 patients with CRC who received surgical treatment in the Department of General Surgery, Affiliated Hospital of Nantong University from January 2016 to February 2018 were analyzed. Preoperative CYFRA 21-1, CEA, CA19-9 and pathological data of the study subjects were collected. Determine the cut-off value of CYFRA 21-1 based on the X-tile. Chi-square test or Fisher exact probability test were used to compare clinicopathological features in different CYFRA 21-1 level groups. Univariate and multivariate regression analysis of factors affecting 5-year overall survival (OS) and disease-free survival (DFS). Kaplan-Meier survival curves were used to analyze 5-year differences in OS and DFS in CRC patients with different levels of CYFRA 21-1, CEA and CA19-9. Receiver operating characteristic(ROC) was adopted. ROC curves were used to analyze the prognostic efficacy of CYFRA21-1 for CRC, and nomogram maps were used to predict 1, 3, and 5-year survival rates. The results showed that the optimal cut-off values of serum CYFRA 21-1, CEA and CA19-9 were 4.9 ng/ml, 29.2 ng/ml and 72.8 U/ml, respectively. Different gender, tumor size, location, degree of differentiation, depth of invasion, lymph node metastasis and tumor node metastasis (TNM) classification stage were significantly different between the two groups with high and low CYFRA 21-1, the P-values were 0.018,<0.001,<0.001,<0.001, 0.002, 0.001, 0.003, respectively. CYFRA 21-1 (≥4.9 ng/ml) was an independent risk factor for 5-year OS (HR: 4.008, 95%CI: 2.309-6.958, P<0.001) and DFS (HR: 3.75, 95%CI: 2.227-6.314, P<0.001) in CRC patients. CYFRA 21-1 predicts a 5-year AUC of 0.725 and 0.720 for OS and DFS, respectively, and 0.804 and 0.827 for the combination of CEA and CA19-9. Based on the results of multivariate Cox regression analysis, nomogram graphs of OS and DFS were established, the C-indexes were 0.799 and 0.803, respectively. In conclusion, preoperative serum CYFRA 21-1 level may be an independent risk factor affecting the prognosis of patients with colorectal cancer. The prognostic model established by CYFRA 21-1 combined with CEA, CA19-9 and TNM stages may provide references for the prevention of CRC recurrence and clinical decision-making.

THU683 TERT Promoter Mutations, But Not BRAFV600EMutation, Correlate With The American Thyroid Association And TNM Staging Systems And Predict Outcome Of Differentiated Thyroid Cancer

Abstract Disclosure: N. Mukhtar: None. K. Alhamoudi: None. M. Alswailem: None. H. Al-Hindi: None. A.K. Murugan: None. B. Alghamdi: None. A.S. Alzahrani: None. Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to predict DTC outcome. Our objectives were to study these molecular markers in terms of their interaction and potential incremental prognostic values over the ATA and TNM staging systems. Patients and Methods: We studied 315 non-selected patients, 229 females, 86 males with a median age of 36 years (IQR 24-49). Data were extracted from medical records. BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Persistent disease (PD) included all patients in structurally or biochemically incomplete and indeterminate response as defined by the 2015 ATA guidelines. Data were analysed using Chi-Square and Fisher Exact test and Kaplan Meier analysis. Results: Of 315 patients tested, 138 (43.8%) had BRAFV600E-positive tumors and 77 (24.5%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of PD (P 0.11). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.01) and in TNM stages III and IV than in lower stages (P &amp;lt;0.001). TERT promoter mutations also predicted the outcome being present in 36.4% of patients with PD compared to only 15.6% in those without evidence of disease (P &amp;lt;0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or TERT promoter + BRAFV600E mutations predicted the development of PD in 100% of patients in TNM stage IV or high-risk ATA stage. Conclusions:TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. The combination of high-risk ATA or TNM stage IV with TERT promoter mutations is highly predictive of development of PD predicting PD in 100% of cases with these combinations. Presentation: Thursday, June 15, 2023

High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer

Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening. A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages. Secondary endpoint was the ability of the test to detect advanced precancerous lesions (advanced adenoma or advanced serrated lesion). A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection according to TNM stages was 84% for stage I, 94% for stage II and 96% for stage III (70/73) (P< 0.024). Sensitivity to detect advanced precancerous lesions was 23% with a refined version of the test (including protein and updating bioinformatic thresholding). A blood-based multimodal ctDNA assay detected CRC with high accuracy. This minimally invasive, accessible and convenient assay may help to increase the effectiveness of CRC screening.

How do BRAFV600E and TERT promoter mutations interact with the ATA and TNM staging systems in thyroid cancer?

The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathological-staging systems. We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis. Of 296 patients tested, 137 (46.3%) had BRAFV600E-positive tumors and 72 (24.3%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) (P 0.12). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (P <0.0001). TERT promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems.

Correlations of special AT-rich sequence binding protein 2 and chitinase-3-like protein-1 with sensitivity to paclitaxel chemotherapy for gastric cancer

Abstract Background: Our objective was to examine the associations between special AT-rich sequence binding protein 2 (SATB2) and chitinase-3-like protein-1 (CHI3L1) and the responsiveness to paclitaxel treatment in individuals with gastric cancer. Methods: From March 2018 to October 2020, our hospital collected gastric cancer samples along with adjacent gastric mucosal tissues located more than 5 cm away from the cancerous margin. These samples were obtained from 90 patients who underwent chemotherapy regimens containing paclitaxel. To assess the rates of positive expression of CHI3L1 and SATB2 in gastric cancer and adjacent tissues, the immunohistochemical streptavidin-peroxidase (SP) technique was utilized. Results: The positive expression rate of CHI3L1 was higher in gastric cancer tissues compared to adjacent tissues, while the positive expression rate of SATB2 was lower (P&lt;0.05). Risk factors that influenced the positive expression of CHI3L1 in gastric cancer tissues included the level of differentiation, tumor-node-metastasis (TNM) stage, and the presence of lymph node metastasis (OR&gt;1, P&lt;0.05). Additionally, the positive expression of SATB2 was also affected by TNM stage and lymph node metastasis, which were identified as risk factors (OR&gt;1, P&lt;0.05). In gastric cancer tissues, there was a negative correlation observed between the expressions of CHI3L1 and SATB2 (r&lt;0, P&lt;0.05). According to the analysis results of Kendall’s tau-b (K), it was found that the presence of CHI3L1 had an inverse relationship with the responsiveness to paclitaxel-based chemotherapy in gastric cancer (r=-0.498, P=0.000), while SATB2 exhibited a positive correlation with the sensitivity (r=0.513, P=0.000). During the 3-year follow-up after chemotherapy, the survival rate was 55.55% (50/90). Conclusions: The findings indicate a strong correlation between SATB2 and CHI3L1 with the TNM stage, lymph node metastasis, response to paclitaxel-based chemotherapy, and the overall survival rate of individuals.

The Prognostic and Clinicopathological Roles of Sirtuin-6 in Various Cancers: A Meta-Analysis

Background: SIRT6, a chromatin-associated nuclear protein, exhibits beneficial and pivotal functions in longevity, cardiovascular diseases, and cancer. However, the significant and controversial clinical value of SIRT6 in cancers has not been fully defined. In this manuscript, we performed an updated and comprehensive meta-analysis of all relevant clinical data in order to gain an exhaustive summary of the clinicopathological roles of SIRT6 in various human cancers. Materials and Methods: A systematic literature searching was performed in PubMed, Web of Science, Embase, and CNKI up to April 2019. Studies enrolled in our quantitative meta-analysis were selected according to inclusion and exclusion criteria. Our meta-analysis was performed using total effect analyses and subgroup analyses to evaluate the relationship between SIRT6 expression and overall survival, clinicopathological parameters of multiple types in cancer patients including cancer/noncancer tissues, lymph node metastasis, metastasis, distant metastasis, differentiation, tumor stage and tumor node metastasis (TNM) stage, tumor size, gender, estrogen receptor, and progesterone receptor. The hazard ratios (HRs) or odds ratios (ORs) of the 95% confidence intervals (CIs) were calculated to reveal the risk or hazard association. All analyses were conducted using the Cochrane Collaboration Review Manager 5.3 software. Results: A total of twenty studies comprising 2700 patients from five countries who represented nine cancer types were included to assess the association between SIRT6 immunohistochemical expression and overall survival or clinicopathological characteristics. Cancer type subgroup analysis showed that high SIRT6 expression was associated with worse OS in hepatocellular carcinoma (HR: 1.49, 95% CI: [1.22, 1.81], P &lt; 0.0001, I 2 = 0%), osteosarcoma (HR: 2.05, 95% CI: [1.28, 3.30], P = 0.003, I 2 = 0%), and non-small cell lung cancer (NSCLC) (HR: 1.88, 95% CI: [1.02, 3.47], P = 0.004, I 2 = 73%). In addition, our results demonstrated that SIRT6 expression was statistically significant in noncancer tissues higher than in cancer tissues (OR = 0.32, 95% CI = 0.13–0.79, P = 0.01, random-effects model). Furthermore, it has been shown that SIRT6 expression was well correlated with lymph node metastasis in patients with breast carcinoma (OR = 1.76, 95% CI = 1.17–2.66, P = 0.007, fixed-effects model), the stages of pathological differentiation in cancer patients (OR = 1.53, 95% CI = 1.08–2.18, P = 0.02, fixed-effects model), tumor stages (I–IV) in NSCLC patients (OR = 0.40, 95% CI = 0.20–0.80, P = 0.01, fixed-effects model), and TNM stages in colon cancer patients (OR = 2.41, 95% CI = 1.38–4.20, P = 0.002, fixed-effects model). Nevertheless, there was no detectable correlation between SIRT6 expression and other clinicopathological parameters in total or subgroup analyses. Conclusion: Our current meta-analysis indicates that the expression level of SIRT6 is highly associated with overall survival and clinical features in specific cancers.

CircUSP10 promotes liver cancer progression by regulating miR-211-5p/TCF12/EMT signaling pathway

There is no precise diagnosis or prognosis for liver cancer (LC) using a single biomarker. Circular RNAs (circRNAs) contribute to the pathogenesis of different cancers, but their role in LC is not entirely understood. In this study, circUSP10, an aberrantly expressed circRNA in LC, was screened using the Gene Expression Omnibus database, and its tissue-specific expression was verified using qRT-PCR. In vitro, functional assays and nude mouse tumorigenesis models were used to investigate circUSP10 role in LC. RNA immunoprecipitation and dual-luciferase reporter assays were performed to study the mechanistic relationship between circUSP10, miR-211-5p, and transcription factor 12 (TCF12). We found that circUSP10 expression was upregulated in LC tissues and cells. CircUSP10 expression was linked to tumor size and tumor node metastasis stage and negatively correlated with LC prognosis. In vitro assays confirmed circUSP10-mediated proliferation, migration, and invasion of LC cells and their association with the epithelial-mesenchymal transition (EMT) pathway. Mechanistically, circUSP10 adsorbed miR-211-5p, which regulated TCF12 and promoted tumorigenesis via the EMT signaling pathway. Therefore, our results suggest that circUSP10 may promote LC progression by modulating the miR-211-5p/TCF12/EMT signaling cascade and may serve as a potential biomarker for LC diagnosis and prognosis.

Comprehensive evaluation of serum circHAS2 as a novel diagnostic and prognostic biomarker for gastric cancer.

The diagnosis and screening indicators for gastric cancer (GC) are not satisfactory, resulting in a large number of GC patients being missed and missing the best treatment time. Due to the special structure of circular RNAs (circRNAs), they have a more accurate and powerful ability to detect tumor occurrence. In addition, circHAS2 has been found to promote the proliferation, migration, and invasion of GC cells. Therefore, this study explored the potential of circHAS2 as a biomarker for GC. The expression level of circHAS2 in the specimens was detected by real-time fluorescent quantitative PCR. The molecular characteristics of circHAS2 were verified by agarose gel electrophoresis and Sanger sequencing. The feasibility of the circHAS2 detection method was verified by room temperature placement and repeated freezing and thawing. The diagnostic effect of circHAS2 on GC was evaluated by receiver-operating curveanalysis. The correlation between circHAS2 expression level and clinical pathological parameters was analyzed using the χ2 -test. Kaplan-Meier survival curve analysis was used to analyze the survival situation of the circHAS2 high- and low-expression group. Univariate and multivariate Cox regression analysis was used to evaluate the influencing factors of prognosis in GC patients. CircHAS2 in cells can be secreted into the blood, and its expression level is significantly upregulated in the serum of patients with GC. The expression level of circHAS2 is correlated with the tissue differentiation, tumor node metastasisstaging, classification, and lymph node metastasis of GC patients. CircHAS2 can effectively identify GC and even early GC. In addition, the expression levels of circHAS2 in postoperative GC patients significantly decreased and returned to normal after the second stage of chemotherapy. Finally, the circHAS2 low-expression group had better survival. The upregulated expression of circHAS2 in the serum of GC patients can effectively identify GC and early GC and can be used for effective monitoring of the prognosis of GC patients. In summary, circHAS2 can be used as an effective diagnostic and prognostic marker for GC.

Enhancing prognostic accuracy: a SEER-based analysis for overall and cancer-specific survival prediction in cervical adenocarcinoma patients

BackgroundCervical adenocarcinoma (CA) is the second most prevalent histological subtype of cervical cancer, following cervical squamous cell carcinoma (CSCC). As stated in the guidelines provided by the National Comprehensive Cancer Network, they are staged and treated similarly. However, compared with CSCC patients, CA patients are more prone to lymph node metastasis and recurrence with a poorer prognosis. The objective of this research was to discover prognostic indicators and develop nomograms that can be utilized to anticipate the overall survival (OS) and cancer-specific survival (CSS) of patients diagnosed with CA.MethodsUsing the Surveillance, Epidemiology, and End Result (SEER) database, individuals with CA who received their diagnosis between 2004 and 2015 were identified. A total cohort (n = 4485) was randomly classified into two separate groups in a 3:2 ratio, to form a training cohort (n = 2679) and a testing cohort (n = 1806). Overall survival (OS) was the primary outcome measure and cancer-specific survival (CSS) was the secondary outcome measure. Univariate and multivariate Cox analyses were employed to select significant independent factors and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis was utilized to develop predictive nomogram models. The predictive accuracy and discriminatory ability of the nomogram were assessed by employing metrics such as the calibration curve, receiver operating characteristic (ROC) curve, and the concordance index (C-index).ResultsAge, Tumor Node Metastasis stages (T, N, and M), SEER stage, grade, and tumor size were assessed as common independent predictors of both OS and CSS. The C-index value of the nomograms for predicting OS was 0.832 (95% CI 0.817–0.847) in the training cohort and 0.823 (95% CI 0.805–0.841) in the testing cohort.ConclusionWe developed and verified nomogram models for predicting 1-, 3- and 5-year OS and CSS among patients with cervical adenocarcinoma. These models exhibited excellent performance in prognostic prediction, providing support and assisting clinicians in assessing survival prognosis and devising personalized treatments for CA patients.

Integrating pretreatment MRI-detected nodal features and Epstein-Barr virus DNA to identify optimal candidates for intensity-modulated radiotherapy alone in patients with stage II nasopharyngeal carcinoma

ObjectivesTo develop and validate a prognostic nomogram based on MRI-detected features of retropharyngeal and cervical lymph nodes and Epstein–Barr virus (EBV) DNA in patients with stage II nasopharyngeal carcinoma (NPC) to distinguish low-risk patients for whom intensity-modulated radiotherapy (IMRT) alone is sufficient. MethodsThis retrospective study enrolled 894 patients with stage II NPC (596 and 298 in the training and validation cohorts, respectively) with pretreatment MRI between August 2010 and May 2019. All patients received IMRT with or without additional chemotherapy. We identified independent risk factors using univariate and multivariate Cox regression analyses. Survival was compared using Kaplan–Meier curves with the log-rank test. ResultsIndependent factors derived from the multivariate analysis include cervical nodal necrosis (CNN), the extracapsular spread (ECS) of cervical and retropharyngeal lymph nodes, and gamma-glutamyl transferase (γ-GGT). Nomograms A, B, and C were established based on the clinical [tumor-node-metastasis (TNM) stage + Epstein–Barr virus (EBV) DNA], the clinical-radiological [all independent predictors] and the combined models [the clinical-radiological model + EBV DNA], respectively. Nomogram C (C-index 0.769 [0.718–0.820]) demonstrated better risk discrimination than nomogram B (0.762 [0.715–0.809]), nomogram A (0.619 [0.564–0.674]), and the TNM stage (0.560 [0.509–0.611]). In the low-risk group divided by nomogram C, no significant survival differences were observed between patients treated with radiotherapy (RT) alone and other regimens including additional chemotherapy. ConclusionsThe nomogram combining MRI-detected retropharyngeal and cervical lymph node features with pretreatment EBV-DNA improved the prognostic risk stratification for stage II NPC.

Long non-coding RNA CASC7 is a promising serum biomarker for hepatocellular carcinoma

BackgroundAt present, a large number of studies have found that long non-coding RNAs (lncRNAs) can be used as biomarkers for diagnosis and monitoring prognosis of hepatocellular carcinoma (HCC). The expression of lncRNA cancer susceptibility candidate 7 (CASC7) in HCC has rarely been studied. The purpose of this study was to explore the expression of CASC7 and its correlation with clinical features, and to further analyze its diagnostic value in HCC.MethodsSerum samples were collected from 80 patients with HCC, 80 patients with chronic hepatitis B (CHB), and 80 healthy people. The expression level of serum CASC7 was detected by droplet digital PCR. Appropriate parametric and nonparametric tests were used for data analysis.ResultsThe results showed that the expression of CASC7 in serum of patients with HCC was significantly higher than that of patients with CHB (median: 8.8 versus 2.2 copies/µl, p < 0.001) and healthy controls (median: 8.8 versus 3.8 copies/µl, p < 0.001). High expression of serum CASC7 was significantly correlated with tumor number (p = 0.005), intrahepatic metastasis (IM) (p < 0.001), tumor size (p = 0.007) and tumor-node-metastasis (TNM) stage (p = 0.008). The area under the curve (AUC) of CASC7 to distinguish HCC patients from CHB patients and healthy controls was 0.808 (95% CI: 0.742–0.874) at the cut-off value of 7.24 copies/µl with 63.8% sensitivity and 95.2% specificity.ConclusionsThis study suggested that CASC7 was significantly up-regulated in serum of patients with HCC and closely related to tumor number, IM, tumor size and TNM stage, which may serve as a promising diagnostic biomarker.