Metastatic Status Of Patients Research Articles

Correlation of High Eosinophil Count Levels in Blood with Metastasis in Colorectal Carcinoma

Background: Eosinophils are bone marrow-derived granulocytes in peripheral blood and tissues primarily involved as effector cells in colorectal cancer metastasis. High levels of eosinophils correlate with poor prognosis in colorectal cancer. Aim: To prove the correlation between increased levels of eosinophils with clinical stage according to the TNM system and metastatic status in patients with colorectal carcinoma. Methods: An analytical cross-sectional study was conducted from July 2020 to June 2021 at Prof. Dr. IGNG Ngoerah Hospital. Data analysis in this study consisted of univariate analysis, bivariate analysis, and multivariate analysis using SPSS IBM version 23. Results: Obtained 40 subjects patient colorectal cancer where men were 25 (62.5%), mean age ± SD53.15 ± 12.5 years, normal nutritional status 29 (72.5%), most locations in the rectum 16 (40%), followed by descending colon 15 (37.5%), the most clinical-stage IVA 13 (32.5%), lung metastases 12 (30%) with adenocarcinoma type 34 (90%). The average level of eosinophils±SDobtained445.63±283.03. The correlation between eosinophil levels and the clinical stage is strongly positive (r = 0.604; p < 0.001), and with the incidence of distant metastases, a strong positive correlation (r = 0.651; p<0.001). Conclusion: There is a statistically significant correlation between increased levels of eosinophils in the blood in metastases and stages colorectal cancer patients, where the higher the eosinophil count levels, the higher the stage and an increase in the incidence of metastases.

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

Cholangiocarcinoma (CCA) is a malignant disease with a poor prognosis, and several studies have been conducted using different molecular markers as a tool for CCA diagnosis, including Clonorchis sinensis (CS)-CCA. We initially identified the expression profiles of the three markers of interest, HMGB1, SOX9, and YAP1, using GSE (GSE76297 and GSE32958) datasets. Upregulated levels of these three proteins were detected in CCA samples compared to those in normal samples. To clarify this issue, 24 human CCA tissues with paired adjacent normal tissues were evaluated using immunohistochemical staining. Of the three markers, the total cellular staining intensities were scanned, and subcellular localization was scored in the nuclear and cytoplasmic regions. The intensities of HMGB1, SOX9, and YAP1 were elevated in CCA tissues than the adjacent normal tissues. Individual scoring of subcellular localization revealed that the expression levels of HMGB1 (nucleus) and YAP1 (nucleus and cytoplasm) were significantly different from the pathologic M stage. Moreover, the translocation pattern was categorized using “site-index”, and the results demonstrated that the overexpression of HMGB1 and SOX9 was mostly observed in both the nucleus and cytoplasm, whereas YAP1 was predominantly expressed in the cytoplasm of tumor cells. Interestingly, the site index of HMGB1 was moderately correlated with the tumor stage (r = 0.441, p = 0.031). These findings imply that the overexpression of subcellular HMGB1 could be associated with the metastatic status of patients with CS-CCA, which was shown to be effective for CS-CCA prognosis.

Radiomic features of axillary lymph nodes based on pharmacokinetic modeling DCE-MRI allow preoperative diagnosis of their metastatic status in breast cancer.

To study the feasibility of use of radiomic features extracted from axillary lymph nodes for diagnosis of their metastatic status in patients with breast cancer. A total of 176 axillary lymph nodes of patients with breast cancer, consisting of 87 metastatic axillary lymph nodes (ALNM) and 89 negative axillary lymph nodes proven by surgery, were retrospectively reviewed from the database of our cancer center. For each selected axillary lymph node, 106 radiomic features based on preoperative pharmacokinetic modeling dynamic contrast enhanced magnetic resonance imaging (PK-DCE-MRI) and 5 conventional image features were obtained. The least absolute shrinkage and selection operator (LASSO) regression was used to select useful radiomic features. Logistic regression was used to develop diagnostic models for ALNM. Delong test was used to compare the diagnostic performance of different models. The 106 radiomic features were reduced to 4 ALNM diagnosis-related features by LASSO. Four diagnostic models including conventional model, pharmacokinetic model, radiomic model, and a combined model (integrating the Rad-score in the radiomic model with the conventional image features) were developed and validated. Delong test showed that the combined model had the best diagnostic performance: area under the curve (AUC), 0.972 (95% CI [0.947-0.997]) in the training cohort and 0.979 (95% CI [0.952-1]) in the validation cohort. The diagnostic performance of the combined model and the radiomic model were better than that of pharmacokinetic model and conventional model (P<0.05). Radiomic features extracted from PK-DCE-MRI images of axillary lymph nodes showed promising application for diagnosis of ALNM in patients with breast cancer.

Axillary lymph node metastasis status prediction of early-stage breast cancer using convolutional neural networks

Deep learning (DL) algorithms have been proven to be very effective in a wide range of computer vision applications, such as segmentation, classification, and detection. DL models can automatically assess complex medical image scenes without human intervention and can be applied as a second reader to provide an additional opinion for the physician. To predict the axillary lymph node (ALN) metastatic status in patients with early-stage breast cancer, a deep learning-based computer-aided prediction system for ultrasound (US) images was proposed. A total of 153 women with breast tumor US images were involved in this study; there were 59 patients with metastasis and 94 patients without ALN metastasis. A deep learning-based computer-aided prediction (CAP) system using the tumor region and peritumoral tissue in ultrasound (US) images were employed to determine the ALN status in breast cancer. First, we adopted Mask R–CNN as our tumor detection and segmentation model to obtain the tumor localization and region. Second, the peritumoral tissue was extracted from the US image, which reflects metastatic progression. Third, we used the DL model to predict ALN metastasis. Finally, the simple linear iterative clustering (SLIC) superpixel segmentation method and the LIME explanation algorithm were employed to explain how the model makes decisions. The experimental results indicated that the DL model had the best prediction performance on tumor regions with 3 mm thick peritumoral tissue, and the accuracy, sensitivity, specificity, and AUC were 81.05% (124/153), 81.36% (48/59), 80.85% (76/94), and 0.8054, respectively. The results indicated that the proposed CAP system could help determine the ALN status in patients with early-stage breast cancer. The results reveal that the proposed CAP model, which combines primary tumor and peritumoral tissue, is an effective method to predict the ALN status in patients with early-stage breast cancer.

Monitoring Value of Serum HER2 as a Predictive Biomarker in Patients with Metastatic Breast Cancer.

PurposeThe aim of this study was to investigate the monitoring value of serum HER2 in patients with metastatic breast cancer.Patients and MethodsWe firstly evaluated the association of serum HER2 levels with tissue HER2 expression and imaging results in 420 breast cancer patients admitted into Tianjin Medical University Cancer Institute and Hospital between April 2016 and December 2018. Secondly, we analyzed serum HER2 levels in breast cancer patients with different metastatic degrees.ResultsThere is a higher correlation between serum HER2 and tissue HER2 in breast cancer patients with stage III (κ=0.670, p<0.001) and stage IV (κ=0.464, p<0.001). Serum HER2 levels were significantly associated with imaging results (κ=0.478, p<0.001). The ROC curve analysis showed that serum HER2 was superior to other serum markers for predicting metastatic breast cancer. Multinomial logistic regression revealed that the patients with higher serum HER2 levels would be more likely to have breast cancer metastasis.ConclusionSerum HER2 levels in breast cancer patients can partly reflect tissue HER2 expression and tumor imaging changes, and serum HER2 may be used as a biomarker for evaluating metastatic status in patients with breast cancer.

CHARACTERISTICS OF ADAPTATIONAL REACTIONS AND MALIGNANT SPREAD IN TUMORS OF VARIOUS LOCATIONS

The character, intensity and quantitative indicator (QI) of general nonspecific adaptational reactions (AR) of the body were studied in patients with lung cancer (LC) or biliopancreatoduodenal cancer (BPDC) with various malignant spread. Poor AR characteristics were associated with the presence of metastases, but did not depend on the surgery volume. AR QI significantly differed depending on the metastatic status in patients with resectable LC receiving similar surgery treatment. AR QI in BPDC patients a day after radical pancreatoduodenal resection was higher than after bypass anastomosis. Thus, the studied AR characteristics demonstrated the state of systemic neuroimmune mechanisms of the nonspecific antitumor resistance of the body.

CCAAT/Enhancer Binding Protein β-Mediated MMP3 Upregulation Promotes Esophageal Squamous Cell Cancer Invasion In Vitro and Is Associated with Metastasis in Human Patients.

Aims: Metastasis is a significant obstacle to curing esophageal squamous cell carcinoma (ESCC). The CCAAT/enhancer binding protein β (C/EBPβ) and matrix metalloproteinase 3 (MMP3) are thought to play key roles in cancer invasion and metastasis. In this study, we aimed to detect whether C/EBPβ-mediated tumor invasion was dependent on MMP3. In addition, we determined whether C/EBPβ upregulation was associated with MMP3 levels and metastatic status in patients with ESCC. Materials and Methods: A total of 126 patients with ESCC were recruited for this study. The mRNA and protein levels of C/EBPβ and MMP3 in ESCC cell lines and specimens from ESCC patient were determined by reverse transcription-polymerase chain reaction and western blot, respectively. Tumor cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The correlation between C/EBPβ and MMP3 expression was determined by Pearson's correlation analysis. Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBPβ overexpression and downregulated by C/EBPβ siRNA in KYSE150 cell cultures. The promotion of ESCC cell invasion through C/EBPβ was inhibited by MMP3 siRNA. The level of C/EBPβ was correlated with MMP3 and metastatic status in patients with ESCC. Conclusions: C/EBPβ upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in ESCC.

Tumor-infiltrating lymphocyte as a prognostic biomarker in stage IV colorectal cancer should take into account the metastatic status and operation modality.

BackgroundAlthough tumor-infiltrating lymphocytes (TILs) have been understood for years as a favorable prognostic factor for colorectal cancers (CRCs) after complete surgical resection, its prognostic role in metastatic CRC (mCRC) remains poorly defined, and it is largely unknown how this prognostic benefit relates to the metastatic status and operation modality.Materials and methodsAfter reviewing 2215 consecutive cases of surgically resected CRC, 332 patients newly diagnosed with stage IV CRC and treated at the Sun Yat-Sen University Cancer Center between 2009 and 2014 were included. H&E-stained (HES) slides from surgical specimens were evaluated for the extent of TILs. The primary end point was overall survival (OS). Cox proportional hazards regression was conducted to determine the prognostic significance of TILs. All statistical tests were 2-sided.ResultsHES slides from primary tumor samples were evaluable for 302 of the 332 included cases. Among the 302 patients, 105 patients (34.8%) were classified as high TIL, the remaining 197 (65.2%) were defined as low TIL. In the univariate analysis, TILs were significantly associated with better OS (P=0.015). Multivariable analysis confirmed that high TIL strongly predicted better survival (hazard ratio =0.62, 95% CI: 0.44–0.89, P=0.008), independent of other patients’ clinicopathological characteristics. Stratified analysis revealed a prognostic benefit of high TIL for patients in the subgroup with non-oligometastatic disease (P=0.002), ≥2 metastatic organs (P=0.006), and non-metastasectomy (P=0.005). By contrast, oligometastatic disease, 1 metastatic organ, or metastasectomy fully abrogated the prognostic effect of TIL.ConclusionOur findings indicate that the level of TILs can be used to predict the outcome for patients with mCRC; however, the operation modality and the metastatic status of patients should also be taken into account.

MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2.

miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis.

Increased EphB2 expression predicts cholangiocarcinoma metastasis.

The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P = 0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P = 0.034 and P = 0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P = 0.012 and P = 0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA.

Genomic profiling and identification of high‐risk tumours in uveal melanoma by array‐CGH analysis of primary tumours and liver metastases

Abstract Purpose Current therapeutic efforts in Uveal Melanoma are directed toward detection of liver metastases at an earlier stage and adjuvant systemic therapy in high risk patients. Beside clinical and histological features, specific cytogenetic alterations, particularly monosomy 3 and gain of 8q, are strongly associated with metastasis. Methods A series of of 78 ocular tumours (OT) (median follow‐up 54 mo.)and of 66 liver metastases (LM), was analysed by CGH on a genome‐wide BAC/DNA microarray (CIT, INSERM U830), with a 1 Mbase average resolution. Correlations were looked for between genomic profiles of OT and the metastatic status of patients, and a prognostic classifier was built, in order to identify tumour profiles of high risk patients. Results Hierarchical clustering shows that status of chromosome 3 defines two groups of genomic profiles in OT and LM: group 1, with disomy 3, and group 2, with monosomy 3. Seven OT show a partial loss of chr 3, with a minimal deletion of 8.9 Mbase, distal to 3p25.3. Groups 1 and 2 can be subdivided in subgroups according to the presence of additional imbalances. Same genomic groups are found in OT and LM, but with different frequencies. The disomy 3 group represents 20% of metastases. A prognostic classifier including the status of chromosomes 3, 6p, 8p, 8q, 16q, and the position of breakpoint in 8q gains, leads to the best prediction performance in this sample (82%). Conclusion Genomic profiling by array‐CGH, combined with the allelic status of chromosome 3, should be a robust and reliable approach for identifying high‐risk patients eligible for LM screening and adjuvant systemic therapy.