Tumor Vascular Invasion Research Articles

Analysis of the safety and effectiveness of TACE combined with targeted immunotherapy in the treatment of intermediate and advanced hepatocellular carcinoma.

To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune and targeted therapy in unresectable hepatocellular carcinoma (HCC). Prospective analysis of 23 patients with intermediate or advanced primary HCC treated at the Department of Hepatic Surgery, The First Affiliated Hospital of the University of Science and Technology of China from July 2019, including 11 cases treated with TACE alone and 12 cases treated with TACE combined with targeted therapy. The basal indexes of patients in the two groups were compared, and the response during treatment was observed; regular follow-up was performed to assess the efficacy of tumor treatment. Compared with TACE treatment alone, the objective response rate (ORR) was significantly higher in the TACE combined with targeted treatment group (50.0% vs 36.4%), with a higher success rate of surgical conversion (33.3% vs 18.2%) and a significantly longer progression-free survival (PFS) (20.5 ± 2.9months vs 11.6 ± 2.9months). Multifactorial regression analysis identified tumor vascular invasion as an independent prognostic factor affecting HCC. No patient experienced catheter retention-related complications during treatment, and there were no intolerable adverse effects. TACE combined with targeted treatment for intermediate to advanced unresectable HCC was effective, with good tumor responsiveness, high surgical conversion rate, and safe and controllable adverse reactions during treatment.

Exploration of prognosis and immunometabolism landscapes in ER+ breast cancer based on a novel lipid metabolism-related signature.

Lipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs). Samples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry. Two LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149). This is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.

Clinicopathological evaluation of cancer-associated fibroblast markers in colorectal cancer (histopathological and immunohistochemical study)

Background and objectives Worldwide, colorectal cancer is considered one of the most common cancer mortality causes. Recent studies have documented that cancer-associated fibroblasts (CAFs) evoke neoangiogenesis and tumor growth for different tumors. Our study analyzed CAF markers, including α-smooth muscle actin (α-SMA), D2-40 (antibody recognizing podoplanin), and vessel markers, including CD31, for 44 colorectal cancer cases. The association between CAF markers and vessel markers with clinicopathological factors was investigated. Furthermore, the association between CAF markers with each other and their association with vessel markers was analyzed and correlated with different clinical parameters like tumor size, grade, and staging. Materials and methods Forty-four paraffin-embedded colectomy specimens were evaluated pathologically for α-SMA, D2-40 (antibody recognizing podoplanin), and CD31 (histopathological and immunohistochemical study). Results Out of forty-four cases studied, 21 (47.7%) males and 23 (52.3%) females with a mean age of 46.20 (SD ±10.619) years old. D2-40 positivity was localized to the peritumoral area, while α-SMA was detected in both intratumoral and peritumoral areas. α-SMA ahd low expression (scores 0 and 1) in three (6.8%) cases and high expression (scores 2 and 3) in 41 (93.2%) cases. Neoangiogenesis and microvessel density were estimated and calculated in intratumoral and peritumoral areas by CD31 expression. The mean±SD of CD31 was 38.34 ± 14.12. Lymphatic vessel density was also estimated and calculated by the D2-40 expression, and the mean±SD of D2-40 was 48.52 ± 13.72. Significant relationships were found between α-SMA expression, D2-40 expression, CD31 expression, and stromal fibroblast proliferation with each other and with tumor size, tumor stage, tumor grade, lymph node metastasis, and deposits. Conclusions Our study results indicated that individual CAFs might have different expression patterns and strength effects for tumor invasion and vascular invasion in colorectal cancer stroma. These findings may evoke novel therapeutic strategies for colorectal cancer treatment and prognosis.

Pathological features associated with metastasis in patients with early invasive (pT1) colorectal carcinoma in colorectal polyps.

Colorectal carcinoma (CRC) arising in a colorectal polyp with invasion limited to the submucosa is sufficiently treated by complete endoscopic resection alone in many cases. Histological features of the carcinoma including tumour size, vascular invasion and poor tumour differentiation or evidence of de-differentiation, such as tumour budding, are associated with a higher risk for metastasis such that oncological resection is recommended. However, most malignant polyps with these features do not have lymph node metastases at the time of resection, so there is a need for better refinement of the histological risk features. A total of 437 consecutive colorectal polyps with submucosal invasive carcinoma from a single centre, 57 of which had metastatic disease, were supplemented by 30 cases with known metastatic disease from two additional centres. Clinical and histological features of the polyp cancers were reviewed looking for differences between the 87 cancers with metastatic disease and the remaining cases without metastasis. A subgroup of 204 polyps removed intact was also analysed to ensure maximum histological accuracy. This study confirmed larger invasive tumour size, vascular invasion and poor tumour differentiation as adverse predictive features. Prominent peritumoral desmoplasia and high cytological grade were additional adverse features. A predictive logistic regression model comprised of (i) presence of any form of vascular invasion; (ii) presence of high tumour budding (BD3); (iii) width of invasive tumour component > 8 mm; (iv) depth of invasive tumour > 1.5 mm; and (v) the finding of prominent expansile desmoplasia located within and beyond the deep invasive edge of the carcinoma, showed excellent performance in predicting metastatic disease.

Transmembrane protein 147, as a potential Sorafenib target, could expedite cell cycle process and confer adverse prognosis in hepatocellular carcinoma.

TMEM147 was identified as a core component of ribosome-bound translocon complex at ER/NE. So far, sparse studies reported its expression profiling and oncological implications in hepatocellular carcinoma (HCC) patients. Here we inspected TMEM147 expression levels in HCC cohorts from public databases and tumor tissues. TMEM147 was augmented at transcriptional levels (p < 0.001) and protein levels in HCC patients. A series of bioinformatics tools implemented in R studio were orchestrated in TCGA-LIHC to evaluate the prognostic significance, compile relevant gene clusters, and explore the oncological functions and therapy responses. It is suggested that TMEM147 could predict poor clinical outcomes effectively and independently (p < 0.001, HR = 2.231 for overall survival (OS) vs. p = 0.04, HR = 2.296 for disease-specific survival), and was related to risk factors including advanced histologic tumor grade (p < 0.001), AFP level (p < 0.001) and vascular invasion (p = 0.007). Functional enrichment analyses indicated that TMEM147 was involved in cell cycle, WNT/MAPK signaling pathways and ferroptosis. Expression profiling in HCC cell lines, mouse model, and a clinical trial revealed that TMEM147 was a considerable target and marker for adjuvant therapy in vitro and in vivo. Subsequentially, in vitro wet-lab experimentation authenticated that TMEM147 would be downregulated by Sorafenib administration in hepatoma cells. Lentivirus-mediated overexpression of TMEM147 could promote cell cycle progression from S phase into G2/M phase, and enhance cell proliferation, thus attenuating drug efficacy and sensitivity of Sorafenib. Further explorations into TMEM147 may inspire a fresh perspective to predict clinical outcomes and improve therapeutic efficacy for HCC patients.

Preoperative low muscle mass and malnutrition affect the clinical prognosis of locally advanced gastric cancer patients undergoing radical surgery.

Gastric cancer is a common and highly aggressive malignant tumor of the gastrointestinal tract that poses a serious threat to human life and health. As the clinical symptoms of early gastric carcinoma are not obvious, many patients are diagnosed in the middle or late stages. With the advancement of medical technology, gastrectomy has become a safer surgical procedure, but it still has a high recurrence and mortality rate after surgery. The prognosis of gastric cancer patients after surgery is not only related to tumor-related factors (i.e., tumor stage) but the patient's nutritional status. This study aimed to investigate the effect of preoperative muscle mass combined with the prognostic nutritional index (PNI) on clinical prognosis in locally advanced gastric carcinoma. The clinical data of 136 patients with locally advanced gastric carcinoma diagnosed by pathology and undergoing radical gastrectomy were retrospectively reviewed. To analyze the influencing factors of preoperative low muscle mass and its correlation with the prognostic nutritional index. Patients with both low muscle mass and low PNI (≤46.55) were assigned a score of 2, and those with only one or neither of these abnormalities were assigned a score of 1 or 0, respectively, according to the new prognostic score (PNIS). The relationship between PNIS and clinicopathological characteristics was analyzed. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Low muscle mass was associated with a lower PNI (P < 0.01). The optimal cut-off value of PNI was 46.55, the sensitivity was 48%, and the specificity was 97.1%. There were 53 (38.97%), 59 (43.38%), and 24 patients (17.65%) in the PNIS 0, 1, and 2 groups, respectively. A higher PNIS and advanced age were independent risk factors for postoperative complications (P < 0.01). The overall survival rate in patients with PNIS 2 score was significantly poorer than in patients with scores of 1 or 0 (3-year OS: 45.8% vs 67.8% vs 92.4%, P < 0.001). A Multivariate Cox hazards analysis showed that PNIS 2, depth of tumor invasion, vascular invasion, and postoperative complications were independent predictors of the poor 3-year survival in patients with locally advanced gastric cancer. The combination of muscle mass and the PNI score system can be used to predict the survival outcome of patients with locally advanced gastric cancer.

A case of spontaneous ovarian malignant neoplasm rupture and life-threatening massive intra-abdominal bleeding

Although ovarian cancer is the second most common gynecological cancer, it is the most common gynecological malignancy that causes death. Approximately 75% of the patients are diagnosed at an advanced stage, and high-grade serous-type ovarian cancer is detected in most of these patients. The final pathology result in our case was high-grade serous ovarian carcinoma. Our patient, 39 years old, applied to our emergency department with complaints of inability to urinate for three days and new onset abdominal pain. We were consulted because of detection of an 11 cm solid mass and globe vesicle in the pelvic region detected on the computed tomography (CT) taken in the emergency department. The patient's initial hemoglobin value was 11.2 g/dL and the beta-human chorionic gonadotropin (ß-HCG) value was negative. During the follow-up, the patient’s hemoglobin values were 9.2 and then decreased to 8.6, 8.1, and 6.5 g/dL after which hypotensive shock developed in the patient. The patient was taken for an emergency laparotomy. Intra-operatively, 1500 mL of intra-abdominal hemorrhagic fluid and diffuse tumor fragments were observed. In the right adnexal area, approximately 11 cm of ruptured tumor tissue, which may originate from the ovary or uterus, was observed. It was observed that the Douglas pouch and uterine, internal iliac , and some parts of the external iliac arteries were extensively invaded by the tumor and active bleeding occurred. Total Abdominal Hysterectomy + Bilateral Salpingo-Oopherectomy (TAH+BSO) was performed on the patient. Additional surgical intervention could not be performed because the patient had extensive vascular tumor invasion, heavy bleeding, and was in hypotensive shock. Six anti-bleeding sponges were placed on intra-abdominal bleeding areas. In addition, packing was applied to the patient by placing four sterile compresses and soft drains inside the abdomen. Tranexamic acid was administered to the patient, and six units of red blood cell suspension and four units of fresh frozen plasma were transfused. The patient was transferred by ambulance to a higher institution, which is a gynecological oncology center, for follow-up, treatment, and complementary surgery. In this case, we aimed to draw attention to a rare case of ovarian malignancy rupture and hypotensive shock.

Overexpression of miR-431-5p impairs mitochondrial function and induces apoptosis in gastric cancer cells via the Bax/Bcl-2/caspase3 pathway

To investigate the expression of microRNA miR-431-5p in gastric cancer (GC) tissues and its effects on apoptosis and mitochondrial function in GC cells. The expression level of miR-431-5p in 50 clinical samples of GC tissues and paired adjacent tissues was detected using real-time fluorescence quantitative PCR, and its correlation with the clinicopathological features of the patients was analyzed. A cultured human GC cell line (MKN-45 cells) were transfected with a miR-431-5p mimic or a negative control sequence, and the cell proliferation, apoptosis, mitochondrial number, mitochondrial potential, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production and adenosine triphosphate (ATP) content were detected using CCK-8 assay, flow cytometry, fluorescent probe label, or ATP detection kit. The changes in the expression levels of the apoptotic proteins in the cells were detected with Western blotting. The expression level of miR-431-5p was significantly lower in GC tissues than in the adjacent tissues (P < 0.001) and was significantly correlated with tumor differentiation (P=0.0227), T stage (P=0.0184), N stage (P=0.0005), TNM stage (P=0.0414) and vascular invasion (P=0.0107). In MKN-45 cells, overexpression of miR-431-5p obviously inhibited cell proliferation and induced cell apoptosis, causing also mitochondrial function impairment as shown by reduced mitochondrial number, lowered mitochondrial potential, increased mPTP opening, increased ROS production and reduced ATP content. Overexpression of miR-431-5p significantly downregulated the expression of Bcl-2 and increased the expressions of pro-apoptotic proteins p53, Bcl-2 and cleaved caspase-3 protein. The expression of miR-431-5p is down-regulated in GC, which results in mitochondrial function impairment and promotes cell apoptosis by activating the Bax/Bcl-2/caspase3 signaling pathway, suggesting the potential role of miR-431-5p in targeted therapy for GC.

Role of exosomes in non-small cell lung cancer and EGFR-mutated lung cancer.

As an important mediator of information transfer between cells, exosomes play a unique role in regulating tumor growth, supporting vascular proliferation, tumor invasion, and metastasis. Exosomes are widely present in various body fluids, and therefore they can be used as a potential tool for non-invasive liquid biopsy. The present study reviews the role of exosomes in liquid biopsy, tumor microenvironment formation, and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC). By targeting epidermal growth factor receptor (EGFR) therapy as a first-line treatment for patients with NSCLC, this study also briefly describes the occurrence of EGRF+ exosomes and the role of exosomes and their contents in non-invasive detection and potential therapeutic targets in EGFR-mutated lung cancer.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Multidisciplinary management in the treatment of intrahepatic cholangiocarcinoma.

Association between HULC gene locus rs7763881 polymorphism and recurrence and metastasis after radical resection in hepatocellular carcinoma

Objective: To investigate the association between the expression of long non-coding RNA genes and the HULC rs7763881 polymorphism, recurrence, and metastasis after radical resection in patients with hepatocellular carcinoma (HCC). Methods: Paraffin tissue samples were selected from 426 cases diagnosed with HCC between January 2004 to January 2012. The expression of different genotypes of HULC gene locus rs7763881 in paraffin tissues was detected by PCR, and the association between different genotype expressions and clinical case characteristics of HCC [gender, age, TNM stage, alpha-fetoprotein, tumor maximum diameter (cm), vascular invasion, tumor capsule, tumor grade] was analyzed. Cox proportional risk regression model was used to analyze the correlation between different genotypes and clinicopathological features, prognosis, and recurrence. Survival analysis between different genotypes was performed using the Kaplan-Meier method for a parallel log-rank test. Results: There were 27 (6.3%) cases in the whole group who lost to follow-up. A total of 399 (93.7%) specimens were included in the study, and 105 (26.3%), 211 (52.9%) and 83 (20.8%) were included in the rs77638881 AA, AC, and CC genotypes, respectively. Kaplan-Meier curve showed that the postoperative overall survival and recurrence-free survival rate were significantly higher in patients with the AA than AC/CC genotype (P < 0.05). Univariate analysis showed that the AC/CC genotype was closely related to tumor vascular invasion and recurrence or metastasis of HCC (P < 0.05). Cox multivariate analysis results showed that patients with the AA genotype were taken as references, and the results showed that the risk of recurrence and metastasis in patients with the CA/CC genotype increased to varying degrees, with statistical significance (P < 0.05). Conclusion: The rs7763881 polymorphic loci located on the HULC gene are closely related to HCC recurrence and metastasis after radical resection. Thus, it may be an indicator for evaluating HCC recurrence and metastasis.

Abstract P6-01-32: Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients

Abstract Introduction: Treatment of early-stage beast cancer (BC) has changed since recent evidence showed that neoadjuvant chemotherapy (NAC) can reduce residual tumor cellularity (RTC) and improve patient outcomes. Achieving a pathologic complete response (pCR) has been associated with significantly improved disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). However, among patients treated with NAC, few experience pCR, while approximately 60-80% of them achieve a pathologic partial response (pPR). In previous studies, BC patients with different grades of pPR have been usually grouped and analyzed together, with inconsistent results and unclear prognostic significance. Objectives: The primary aims of this study were to describe the clinical and treatment characteristics of BC patients treated with NAC, to identify independent predictive factors of pCR, and to compare the oncologic outcomes between patients achieving pCR or pPR. The secondary aim of this study was to measure the RTC of BC patients with pPR and to compare the outcomes of patients with different RTC in order to improve prognostic information. Methods: All the consecutive BC patients undergoing NAC at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy) between October 2006 and April 2020 and their corresponding post-operative pathology slides were reviewed. The following exclusion criteria were used: excisional biopsy or debulking surgery as first BC operation, patients with a previous BC diagnosis or other prior or synchronous malignancies, male patients, unknown NAC regimen, disease progression during NAC, and follow-up ≤12 months. Results: A total of 495 BC patients received NAC. Overall, 148 (29.9%) patients achieved pCR, while 347 (70.1%) had pPR, and median RTC was 40%. At multivariable analysis, 3 independent factors predicting pCR were identified. Tumor stage pre-NAC (cT1-2 84.5% versus cT3-4 15.5%, odds ratio (OR)=0.119, 95% confidence interval (95%CI)=0.048-0.189, p=0.001), BC sub-type (HER2-enriched 54.7% versus triple-negative 29.8% versus luminal-like 15.5%, OR=2.178, 95%CI=2.055-2.301, p=0.001), and vascular invasion (absence 98.0% versus presence 2.0%, OR=0.022, 95%CI=0.004-0.090, p=0.001). Patients with BC undergoing NAC and achieving pCR presented statistically significant longer DFS, DDFS, and OS (p = &amp;lt; 0.001). Patients with RTC &amp;lt; 40% presented statistically significant better DFS and DDFS (p = 0.033, p = 0.015, respectively). However, no statistically significant difference in terms of OS was observed between RTC &amp;lt; 40% and RTC ≥40% groups (p = 0.148). Conclusions: Tumor stage pre-NAC, BC sub-type, and vascular invasion are significantly and independently associated with pCR. Patients with pCR present a better prognosis compared to patients with pPR in terms of DFS, DDFS, and OS. Measurement of RTC in BC patients with pPR improves the prognostic information that can be obtained from the assessment of the pathologic response. Different patterns of residual disease play an important role in predicting the risk of subsequent loco-regional and distant recurrence, and patients with RTC &amp;lt; 40% present significantly better DFS and DDFS. Citation Format: Damiano Gentile, Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Simone Di Maria Grimaldi, Erika Barbieri, Wolfgang Gatzemeier, Lorenzo Scardina, Ersilia Biondi, Flavia Jacobs, Giulia Vatteroni, Corrado Tinterri. Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-32.

Preoperative monocyte to high-density lipoprotein ratio as a predictor of survival outcome of gastric cancer patients after radical resection.

Aim: This study aimed to verify the prognostic value of monocyte to high-density lipoprotein ratio (MHR) in gastric cancer patients after radical resection. Methods: The Cox proportional hazards model was used to determine the risk variables for survival. Results: Older age (>60years) (hazard ratio [HR]: 1.832; 95% CI:1.167-2.725; p =0.009), advanced tumor node metastasis stage (p <0.05), lymphatic invasion (HR: 1.639; 95% CI: 1.114-3.032; p <0.05), vascular invasion (HR: 2.002; 95% CI: 1.246-5.453; p =0.028) and high MHR (HR: 1.154; 95% CI: 1.062-2.315; p =0.021) were independent poor prognostic factors for gastric cancer patients after radical resection. Conclusion: Older age, advanced tumor node metastasis stage, lymphatic invasion, vascular invasion and high MHR were independent poor prognostic factors for gastric cancer patients after radical resection.

Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer

BackgroundHsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC. MethodsThe transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted. ResultsOverall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p. ConclusionsHsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

Establishment and validation of a predictive model of recurrence in primary hepatocellular carcinoma after resection.

In recent years, nomogram prediction models have been widely used to evaluate the prognosis of various diseases. However, studies in primary hepatocellular carcinoma (HCC) are limited. This study sought to explore the risk factors of recurrence of patients with primary HCC after surgical resection and establish a nomogram prediction model. The data of 424 patients with primary HCC who had been admitted to the Wuhan Third Hospital were retrospectively collected. The patients were followed-up for 5 years after surgery. The patients were divided into the recurrence group (n=189) and control group (n=235) according to whether the cancer recurred after surgery. The differences in the clinical characteristics between the two groups were analyzed. The risk factors of recurrence after surgical resection of primary HCC were also analyzed, and a prediction model was then established using R4.0.3 statistical software. There were significant statistical differences between the two groups in terms of the tumor size, systemic immune-inflammation (SII) index, the number of lesions, tumor differentiation degree, ascites, vascular invasion, and portal vein tumor thrombus (P<0.05). The multivariate regression analysis showed that multiple foci, poorly differentiated tumors, ascites, vascular invasion, and portal vein tumor thrombus were risk factors for the recurrence of primary HCC in patients after surgical resection (P<0.05). The data set was randomly divided into a training set and verification set. The sample size of the training set was 297, and the sample size of the verification set was 127. The area under the receiver operating characteristic (ROC) curve of the training set was 0.866 [95% confidence interval (CI): 0.824-0.907], and the area under the ROC curve of the validation set was 0.812 (95% CI: 0.734-0.890). The Hosmer-Lemeshow Goodness-of-Fit Test was used to test the model with the validation set (χ2=11.243, P=0.188), which indicated that the model had high value in predicting the recurrence of primary HCC after surgical resection. This model had high value in predicting the recurrence of primary HCC in patients after surgical resection. This model could assist clinicians to assess the prognosis of patients. Intensive treatment for high-risk patients might improve the prognosis of patients.

Computed tomography-based evaluation for normal adrenal gland size independent of body weight in dogs.

Computed tomography (CT) is useful for evaluating the anatomical position of the adrenal gland and the presence of adrenal tumor (AT) metastasis or vascular invasion from ATs. To determine a weight-independent reference for adrenal gland size in normal dogs using CT. The medical records database of Gifu University was searched for data collected from April 2010 to December 2015 for records of dogs that underwent abdominal CT. The CT images were retrospectively analyzed using a Digital Imaging and Communications in Medicine viewer. The ratios of the minor axes of the adrenal glands to the height of the spinal cavity were investigated. In total, 939 dogs were included. The left and right adrenal minor axes showed a moderate positive correlation with body weight (right: r = 0.61, p < 0.05; left: r = 0.54, p < 0.05). The L4 spinal cavity height showed a strong positive correlation with body weight (r = 0.82, p < 0.05). The left and right adrenal minor axis/L4 spinal cavity ratio did not correlate with body weight (right: r = 0.02, p = 0.53; left: r = -0.082, p < 0.05). The 95% confidence intervals of the adrenal minor axis/L4 spinal cavity ratios were as follows: right: 0.5-1.3 and left: 0.5-1.4. These results indicate that the adrenal minor axis/L4 spinal cavity ratio can be used as an index of adrenal gland size that is not affected by body weight. Patients in whom the adrenal minor axis/L4 spinal cavity ratio exceeds the upper limit (right 1.3, left 1.4) may have adrenal swelling.

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

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

Upregulation of SERPINE2 Results in Poor Prognosis of Hepatoblastoma via Promoting Invasion Abilities.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. High-risk patients, especially those with tumor metastasis, have poor prognosis. Serpin family E member 2 (SERPINE2) is overexpressed in a variety of tumors, especially adenocarcinoma, and promotes tumor invasion and metastasis. The function and mechanism of SERPINE2 in HB are still unclear. The purpose of this study was to investigate the potential clinical prognostic value and molecular mechanism of SERPINE2 in HB. We performed bioinformatics analyses on HB microarray data GSE131329 to study the role of SERPINE2. The expression level of SERPINE2 in HB and its clinical significance were further analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. After constructing the SERPINE2 overexpression and knockdown in HepG2 and HUH6 cells, the 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, Transwell experiment, and apoptosis assay were performed to explore the role of SERPINE2 in HB progress. Upregulation of SERPINE2 was found in HB tissues and was associated with a poor prognosis. Moreover, the SERPINE2 expression was related to tumor size, vascular invasion, and tumor metastasis. The Cox regressions show that high SERPINE2 expression is an independent risk factor for HB. SERPINE2 overexpression remarkably enhanced HB cell migration and invasion and suppressed apoptosis, while knockdown of SERPINE2 exerted the opposite effect. In addition, SERPINE2 facilitated the epithelial to mesenchymal transformation (EMT) phenotype of HB cells in vitro. Our findings indicated that SERPINE2 accelerates HB progression, suggesting that SERPINE2 may be a potential prognostic biomarker and an underlying therapeutic target for HB.

Overexpression of miR-607 inhibits hepatocellular carcinoma cell growth and metastasis by down-regulating TRPC5

To investigate the clinical implications of abnormal expression of miR-607 in hepatocellular carcinoma (HCC) and its influence on HCC cell proliferation and migration. The expression of miR-607 in 45 pairs of HCC and adjacent tissues were detected with real-time PCR, and the correlation between miR-607 expression and clinicopathological features of the patients was analyzed. The effects of transfection with miR-607 mimics on proliferation, apoptosis, migration and invasion of two HCC cell lines (Huh-7 and HCCLM3) were evaluated using CCK-8 assay, flow cytometry, wound-healing assay and Transwell assay. A dual-luciferase reporter system was used to detect the direct binding between miR-607 and 3'-UTR of TRPC5 mRNA. Western blotting was used to measure the expressions of TRPC5, CCND1, MMP2 and phosphorylated Akt in the HCC cells. The expression of miR-607 was significantly decreased in HCC tissues (P=0.029) and HCC cell lines (P < 0.05). In HCC patients, a low expression of miR-607 was associated with a larger tumor size (>5 cm, P=0.031), vascular invasion (P=0.027) and advanced TNM stages (Ⅲ + Ⅳ, P=0.015). In the two HCC cell line, overexpression of miR-607 significantly inhibited cell proliferation, migration, and invasion and enhanced cell apoptosis (P < 0.05). The results of dualluciferase reporter assay confirmed that TRPC5 was a direct target of miR- 607 in HCC cells. Overexpression of miR-607 significantly inhibited the expressions of TRPC5, CCND1, and MMP2 and suppressed Akt phosphorylation in HCC cells (P < 0.05). A low expression of miR-607 in HCC is associated with poor clinicopathological phenotypes of HCC. Overexpression of miR-607 inhibits HCC growth and metastasis possibly by down- regulating TRPC5, which causes Akt signaling inactivation.

Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients.

Many biomarkers have predictive value for overall survival (OS) and disease-free survival (DFS) in tumor patients. However, the role of indirect bilirubin (IBIL) in local advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) has not been studied. To explore the predictive value of IBIL before nCRT (pre-IBIL) for the OS and DFS of LARC patients treated with nCRT. A total of 324 LARC patients undergoing nCRT with total mesorectal excision (TME) were enrolled. Preoperative clinical features and postoperative pathological characteristics were collected. Cox regression analysis was performed, and a Cox-based nomogram was developed to predict OS and DFS. We also assessed the predictive performance of the nomogram with calibration plots and receiver operating characteristic (ROC) curves. Among 324 patients, the median pre-IBIL was 6.2 μmol/L (interquartile range: 4.6 μmol/L-8.4 μmol/L). In the Cox multivariate regression analysis, we found that pre-IBIL, smoking history, tumor regression grade (TRG), vascular invasion, and carbohydrate antigen 19-9 before nCRT (pre-CA19-9) were predictors of OS. Additionally, pre-IBIL, body mass index (BMI), nCRT with surgery interval, TRG, and vascular invasion were predictors of DFS. Predictive nomograms were developed to predict 5-year OS and 5-year DFS with area under the ROC curve values of 0.7518 and 0.7355, respectively. Good statistical performance on internal validation was shown by calibration plots and ROC curves. This study demonstrated that pre-IBIL was an independent prognostic factor for OS and DFS in LARC patients treated with nCRT followed by TME. Nomograms incorporating pre-IBIL, BMI, smoking history, nCRT with surgery interval, TRG, vascular invasion, and pre-CA19-9 could be helpful to predict OS and DFS.