High Expression of CLDN 18.2 is Associated with Poor Disease-Free Survival of HER-2 Positive Gastric Cancer.

Background: Anti-claudin (CLDN) 18.2 therapy has been proven to be effective in treating advanced gastric cancer with negative human epidermal growth factor receptor 2 (HER-2). This study purposed to investigate the relationship of CLDN 18.2 expression with prognosis of HER-2-positive gastric cancer patients. Objective: To investigate the expression of claudin (CLDN) 18.2 in Human epidermal growth factor receptor 2 (HER-2) positive gastric cancer patients after radical resection and its relationship with gastric cancer prognosis. Methods: A total of 55 postoperative HER-2-positive gastric cancer patients were included in this study. CLDN 18.2 protein was detected by immunohistochemistry, and detailed clinical and pathological information was collected. Factors considered potentially important in the univariate analysis were included in the multivariate analysis, which involved COX regression to find the independent prognostic factors affecting disease-free survival (DFS). Results: Immunohistochemistry showed that different levels of CLDN 18.2 protein were expressed in HER-2 positive gastric cancer tissues, and the Chi-square analysis showed that the expression level of CLDN 18.2 was significantly correlated with the lymph node stage. Higher expression levels of CLDN 18.2 were found in patients with lymph node positivity and were associated with poor prognosis in HER-2-positive gastric cancer patients. Gastric cancer patients with low and high expressions of CLDN 18.2 had postoperative median DFS of 38.5 months (95% confidence interval (CI) 28.8-48.2 months) and 12.1 months (95% CI, 11.7-41.0 months), respectively. Conclusion: High expression of CLDN 18.2 in HER-2 positive gastric cancer is associated with poor prognosis, and the optimal treatment mode for this population is worth exploring after the approval of anti-CLDN 18.2 drugs.

5-Fluorouracil resistant CRC cells derived exosomes promote cancer-associated fibroblasts secreting more CXCL12.

Background: Chemoresistance is a key reason for treatment failure in colorectal cancer (CRC) patients. The tumor microenvironment of chemoresistant CRC is distinctly immunosuppressive, although the underlying mechanisms are unclear. Methods: The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method. The in-situ expression of transient receptor potential channel 5 (TRPC5) and fibroblast activation protein (FAP) in the CRC tissues was examined by immunohistochemistry. TRPC5 expression levels in the HCT8 and HCT116 cell lines and the corresponding 5-fluorouracil (5-FU)-resistant cell lines (HCT8R and HCT116R) were analyzed by western blotting and RT-PCR. Exosomes were isolated from the HCT8R and HCT116R cells and incubated with colorectal normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs)markers were detected. NFs were also incubated with exosomes isolated from TRPC5-knockdown HCT8R cells, and the changes in intracellular Ca2+ levels and C-X-C motif chemokine ligand 12 (CXCL12) secretion were analyzed. Results: TRPC5 and FAP expression showed positive correlation in the datasets. Immunostaining of CRC tissue specimens further revealed that high TRPC5 and FAP expressions were significantly associated with worse tumor regression. Furthermore, chemoresistant CRC cells expressed higher levels of TRPC5 compared to the chemosensitive cells, and knocking down TRPC5 reversed chemoresistance. Exosomes derived from CRC cells induced the transformation of NFs to CAFs. However, TRPC5-exosomes derived from chemoresistant CRC cells can promote CAFs to secrete more CXCL12. Conclusion: Chemoresistant CRC cells can induce CAFs activation and promote CXCL12 secretion through exosomal TRPC5.

High CTC-TRPC5 Expression Significantly Associated With Poor Prognosis in Radical Resected Colorectal Cancer Patients.

Recurrence is the main reason of treatment failure of redical resected colorectal cancer (CRC). Although some factors including staging and differentiation have been proven to useful for recurrence evaluation, prognosis of certain patients does not conform to this evaluation approach. Circulating tumor cells (CTC) have been found to have prognostic value in CRC, and previous studies on CTC have primarily focused on their numbers. CTC are functionally heterogeneous cell populations, and different CTC subgroups may have different functions and clinical values. In our previous study, we discovered that elevated expression of the transient receptor potential channel TRPC5 was associated with a significantly poor prognosis in CRC. In this study, we collected peripheral blood from CTC-positive CRC patients, identified the TRPC5 protein expression on CTC (CTC-TRPC5), and analyzed the relationship between CTC-TRPC5 expression levels and the prognosis. The results showed that CTC-TRPC5 level is significantly related to the T stage and differentiation of tumors. High level of CTC-TRPC5 is more common in a high T stage as well as poorly differentiated tumors and is significantly associated with shorter disease free survival (DFS). The median DFS of CRC patients with high and low CTC-TRPC5 level was 17.1 and 22.0 months, respectively (p < 0.05). This study revealed a clinically significant CTC subgroup of CRC, providing a new indicator for clinical evaluation of CRC prognosis.

Can 3D pseudo-continuous arterial spin labeling perfusion imaging be applied to predict early response to chemoradiotherapy in patients with advanced nasopharyngeal carcinoma?

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) has been widely applied in patients with advanced nasopharyngeal carcinoma (ANPC). However, limited imaging modality exists on the evaluation of early response to CRT. The purpose of this study was therefore to investigate whether 3D pseudo-continuous arterial spin labeling (3D pCASL) perfusion imaging could predict early response to CRT in ANPC patients. MATERIALS AND METHODS: Seventy ANPC patients who received CRT underwent pre-treatment MRI including 3D pCASL perfusion measurements, and were categorized into response group (RG) and no-response group (NRG) according to RECIST 1.1. Pre-treatment 3D pCASL derived cerebral blood flow (CBF) values in tumors were compared between RG and NRG patients. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal diagnostic cutoff value for CBF in predicting tumor response to CRT. Clinicopathological variables were also analyzed by using univariate and binary logistic regression. The corresponding obtained variables with statistical significance were further applied to create a nomogram in which the bootstrap resampling method was used for calibration. RESULTS: Forty-eight patients in RG had significantly higher pre-treatment CBF values in tumors compared with 22 patients in NRG (P < 0.001). CBF showed the high area under the ROC curve (AUC = 0.843) in distinguishing RG from NRG patients. The corresponding cutoff value for CBF was 103.68 ml/100 g/min, with respective accuracy, sensitivity and specificity of 82.86%, 87.50% and 72.73%. The nomogram was generated by binary logistic regression results, incorporating three variables: CBF value, clinical stage and pathological type. The AUC, accuracy, sensitivity and specificity of the nomogram was respectively 0.893, 84.28%, 81.25% and 90.91% in predicting tumor response to CRT. Moreover, as shown in the calibration curve, a strong agreement was observed between nomogram prediction probability and actual clinical findings (P = 0.309). CONCLUSIONS: 3D pCASL derived CBF in tumor could act as a noninvasive effective biomarker to predict tumor response to CRT in ANPC patients before clinical treatment. Furthermore, the nomogram combining CBF and clinicopathological variables could serve as a novel clinical analysis tool for treatment response prediction.

Preoperative prediction for lauren type of gastric cancer: A radiomics nomogram analysis based on CT images and clinical features.

PURPOSE: To investigate feasibility of predicting Lauren type of gastric cancer based on CT radiomics nomogram before operation. MATERIALS AND METHODS: The clinical data and pre-treatment CT images of 300 gastric cancer patients with Lauren intestinal or diffuse type confirmed by postoperative pathology were retrospectively analyzed, who were randomly divided into training set and testing set with a ratio of 2:1. Clinical features were compared between the two Lauren types in the training set and testing set, respectively. Gastric tumors on CT images were manually segmented using ITK-SNAP software, and radiomic features of the segmented tumors were extracted, filtered and minimized using the least absolute shrinkage and selection operator (LASSO) regression to select optimal features and develop radiomics signature. A nomogram was constructed with radiomic features and clinical characteristics to predict Lauren type of gastric cancer. Clinical model, radiomics signature model, and the nomogram model were compared using the receiver operating characteristic (ROC) curve analysis with area under the curve (AUC). The calibration curve was used to test the agreement between prediction probability and actual clinical findings, and the decision curve was performed to assess the clinical usage of the nomogram model. RESULTS: In clinical features, Lauren type of gastric cancer relate to age and CT-N stage of patients (all p < 0.05). Radiomics signature was developed with the retained 10 radiomic features. The nomogram was constructed with the 2 clinical features and radiomics signature. Among 3 prediction models, performance of the nomogram was the best in predicting Lauren type of gastric cancer, with the respective AUC, accuracy, sensitivity and specificity of 0.864, 78.0%, 90.0%, 70.0%in the testing set. In addition, the calibration curve showed a good agreement between prediction probability and actual clinical findings (p > 0.05). CONCLUSION: The nomogram combining radiomics signature and clinical features is a useful tool with the increased value to predict Lauren type of gastric cancer.

Can Arterial Spin Labeling Perfusion Imaging be Used to Differentiate Nasopharyngeal Carcinoma From Nasopharyngeal Lymphoma?

BACKGROUND: Differentiating nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoma (NPL) is useful for deciding the appropriate treatment. However, the diagnostic accuracy of current imaging methods is low. PURPOSE: To explore the feasibility of arterial spin labeling (ASL) perfusion imaging in the qualitative and quantitative differentiation between NPC and NPL to improve the diagnosis of malignancies in the nasopharynx. STUDY TYPE: Retrospective. POPULATION: Ninety seven patients: NPC (65 cases) and NPL (32 cases), histologically confirmed. FIELD STRENGTH/SEQUENCE: 3T/3D fast spin echo pseudo-continuous ASL imaging with spiral readout scheme, 3D inverse recovery- fast spoiled gradient recalled echo brain volume (BRAVO) imaging. ASSESSMENT: Cerebral blood flow (CBF) images from ASL perfusion imaging were assessed by three radiologists. Each tumor was visually scored based on CBF images. Intratumoral CBF and intramuscular CBF values were obtained from intratumoral and lateral pterygoid muscle areas, respectively. Through dividing intratumoral CBF by intramuscular CBF, normalized CBF (nCBF) was further calculated. STATISTICAL TESTS: Fleiss's kappa and intraclass correlation coefficients (ICCs) were used to assess interobserver agreement among the three readers. The Mann-Whitney U-test was used to compare visual scoring, and an unpaired t-test was performed to compare CBF value between the NPC and NPL groups. The area under the curve (AUC) value was used to quantify the diagnostic ability of each parameter. RESULTS: Good interobserver agreements were validated by high Fleiss's kappa and ICC values (all >0.80). NPCs showed significantly higher visual scores than NPLs (P < 0.05). Both intratumoral CBF and nCBF in NPC were significantly higher than those in NPL (both P < 0.05). Intratumoral CBF showed the highest AUC of 0.861 (P < 0.05) in differentiating NPC (n = 65) from NPL (n = 32), while the AUCs of nCBF and visual scoring were 0.847 and 0.753, respectively. DATA CONCLUSION: For the diagnosis of distinguishing NPC from NPL, ASL perfusion imaging demonstrated high diagnostic efficiency. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Clinical Correlation of Wnt2 and COL8A1 With Colon Adenocarcinoma Prognosis.

Wnt2 mRNA is widely expressed in various tumor tissues. Wnt2 overexpression promotes tumor growth, migration, invasion, and metastasis. However, its underlying molecular action mechanisms and clinical implications in colon adenocarcinoma (COAD) remain unclear. mRNA expression data, obtained from tissue samples, and pathophysiological data of 368 COAD patients were obtained from the Cancer Genome Atlas (TCGA) database. Further, Pearson's correlation analysis was performed to explore the correlation between the expression levels of Wnt2 and other genes in the human genome. Subsequently, a protein-protein interaction (PPI) network was constructed for hub gene identification. Overall survival and significance were determined by Kaplan-Meier analysis, and the log-rank test was used to further identify genes with prognostic significance in COAD from GEO datasets (GSE17538 and GSE39582). Subsequently, 158 tissue samples from Affiliated Hospital of Jiangnan University were used for expression verification. Gene set enrichment analysis (GSEA) was performed on high and low Wnt2 expression datasets to identify potential signaling pathways activated in COAD. In all, 10 hub genes associated with Wnt2 were screened by Pearson's correlation analysis and PPI network, with Wnt2 and COL8A1 having significantly poor prognosis by Kaplan-Meier analysis and log-rank test. Furthermore, high expressions of COL8A1 and Wnt2 were associated with poor survival both in TCGA and GEO cohorts. We further found a correlation between the expressions of Wnt2 and COL8A1 in COAD as per immunohistochemical analysis. To further elucidate the underlying molecular mechanisms of Wnt2 in COAD, we searched for pathways enriched in Wnt2 overexpressing datasets by GSEA. Our findings revealed that high Wnt2 levels were significantly associated with extracellular matrix receptor and focal adhesion pathways. Wnt2 expression correlated with COL8A1 expression in COAD; patients with high Wnt2 and COL8A1 expressions had worse survival outcomes. Pathways identified in this study prompt the molecular role of Wnt2 in COAD and provide directions to further elucidate the involved molecular mechanisms in COAD.

The calcium pump PMCA4 prevents epithelial-mesenchymal transition by inhibiting NFATc1-ZEB1 pathway in gastric cancer.

Epithelial-mesenchymal transition (EMT) is considered as the key mechanism involved in cancer metastasis. Several studies showed that various cell membrane calcium channels play different roles in cancer metastasis. In the present study, the potential role of ATPase plasma membrane Ca2+ transporting 4 (PMCA4) in regulating EMT in gastric cancer (GC) was investigated. GC patients who underwent radical surgery were enrolled in this study. In vitro human GC cell lines MKN45 and NCI-N87 were used, and MKN45 cells were injected in nude mice to evaluate tumor development. Our results showed that low PMCA4 expression was associated with advanced TNM stage and poor prognosis in GC patients. Knockdown of PMCA4 suppressed E-cadherin, grainyhead like 2 (GRHL2) and ovo-like 1 (OVOL1) expression, up-regulated vimentin expression, increased migration and invasion ability, and promoted the resistance to cytotoxic drug. Furthermore, GC cells displayed an elongated fibroblastoid morphology when PMCA4 was knockdown. PMCA4 overexpression resulted in an up-regulated E-cadherin expression and decreased migration and invasion ability. In vivo metastasis assay showed that PMCA4 overexpression resulted in a decreased incidence of lung metastasis. PMCA4 inhibition increased ZEB1 expression and nuclear accumulation of nuclear factor of activated T-cell isoform c1 (NFATc1). EMT induced by PMCA4 inhibition could be prevented by the knockdown of NFATc1 or ZEB1. In addition, cyclosporine A prevented EMT induced by PMCA4 inhibition by suppressing the NFATc1-ZEB1 pathway. Our data identified a novel mechanism in the regulation of EMT in GC, and provided a novel target in the treatment of EMT subtype in GC.

Long Noncoding RNA LINC02163 Accelerates Malignant Tumor Behaviors in Breast Cancer by Regulating the MicroRNA-511-3p/HMGA2 Axis.

Long intergenic nonprotein-coding RNA 02163 (LINC02163) has been reported to be upregulated and work as an oncogene in gastric cancer. The aims of the present study were to determine the expression profile and clinical value of LINC02163 in breast cancer. Additionally, the detailed functions of LINC02163 in breast cancer were explored, and relevant molecular events were elucidated. In this study, LINC02163 was upregulated in breast cancer, and its expression level was closely associated with tumor size, lymph node metastasis, and TNM stage. Patients with breast cancer presenting high LINC02163 expression exhibited shorter overall survival than those presenting low LINC02163 expression. Knockdown of LINC02163 resulted in a decrease in breast cancer cell proliferation, migration, and invasion and an increase in cell apoptosis in vitro. In addition, silencing of LINC02163 impeded breast cancer tumor growth in vivo. Mechanistic investigation revealed that LINC02163 served as a competing endogenous RNA for microRNA-511-3p (miR-511-3p) and consequently upregulated the expression of the high-mobility group A2 (HMGA2), a downstream target of miR-511-3p. Intriguingly, miR-511-3p inhibition and HMGA2 restoration counteracted the effects of LINC02163 deficiency on the malignant properties of breast cancer cells. LINC02163 exerts cancer-promoting effects during the initiation and progression of breast cancer via regulation of the miR-511-3p/HMGA2 axis. Our findings add to our understanding of the roles of the LINC02163/miR-511-3p/HMGA2 pathway as a regulator of breast cancer pathogenesis and may be useful in the development of lncRNA-directed cancer diagnosis, prognosis, and therapy.

Development and validation of a nomogram to predict survival after curative resection of nonmetastatic colorectal cancer.

BACKGROUND: We aimed to develop a clinical applicable nomogram to predict overall survival (OS) for patients with curatively resected nonmetastatic colorectal cancer. METHODS: Records from a retrospective cohort of 846 patients with complete information were used to construct the nomogram. The nomogram was validated in a prospective cohort of 379 patients. The performance of the nomogram was evaluated with concordance index (c-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits respectively, and further compared with AJCC 8th TNM staging and the MSKCC nomogram. Risk stratification based on nomogram scores was performed with recursive partitioning analysis. RESULTS: The nomogram incorporated age, Glasgow prognostic score, pretreatment carcinoembryonic antigen levels, T staging, N staging, number of harvested lymph nodes, and histological grade. Compared with the 8th AJCC staging and MSKCC model, the nomogram had a statistically higher c-index (0.77, 95% CI: 0.73-0.80), bigger areas under the time-dependent ROC curves (AUC at 3 years: 79; at 5 years: 79), and improved clinical net benefits. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort. Nomogram-based risk stratification successfully discriminated patients within each AJCC stage (all log-rank P < .05). CONCLUSION: We established an accurate, reliable, and easy-to-use nomogram to predict OS after curative resection for nonmetastatic colorectal cancer (CRC). The nomogram outperformed the 8th AJCC staging and the MSKCC model and could aid in personalized treatment and follow-up strategy for CRC patients.

SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during the development and progression of the disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it is unclear whether SPZ1 plays a role in suppressing apoptosis, and the molecular mechanism behind SPZ1's suppression of apoptosis in CRC remains unclear. Here, we found that silencing endogenous SPZ1 inhibits cell growth and induces apoptosis, and overexpression of SPZ1 promotes cell growth. These findings were corroborated by in vitro and in vivo studies. Interestingly, SPZ1 overexpressing cells were resistant to 5-fluorouracil, a drug commonly used to treat cancer. Moreover, knocking down SPZ1 led to the activation of caspase through the deregulation of Bim by ERK1/2, we found that CRC tissues had significantly higher SPZ1 and lower Bim expression, and SPZ1HBimL were associated with advanced clinical stage of CRC. Collectively, our findings demonstrate that SPZ1 contributes to tumor progression by limiting apoptosis. SPZ1 reduces apoptosis by altering the stability of Bim, suggesting SPZ1 may serve as a biomarker and therapeutic target for CRC.

Clinicopathological significance of Sox10 expression in triple-negative breast carcinoma.

BACKGROUND: This study aimed to investigate the SRY-related higll-mobility-group box 10 (Sox10) expression in the pathological diagnosis of triple-negative breast cancer (TNBC). Furthermore, its correlation with the clinicopathological characteristics and disease-free survival rate in patients with TNBC was also evaluated to identify the diagnostic utility of Sox10 as a reliable biomarker for the diagnosis and prognosis of TNBC. METHODS: Using immunohistochemistry (IHC), we identified the expression of Sox10, GATA binding protein 3 (GATA-3), forkhead box protein A1 (FOXA1), gross cystic disease fluid protein (GCDFP15), and mammaglobin (MGB) in 376 cases of primary invasive breast cancer, and 77 cases of metastatic breast cancer. The expression of Sox10 in different molecular subtypes of primary invasive breast cancer and metastatic breast cancer were also compared. Furthermore, the correlation between Sox10 expression and clinicopathological parameters and disease-free survival (DFS) of patients with primary TNBC were also analyzed. RESULTS: Expression of Sox10 was only detected in the myoepithelial cells of normal breast tissue, but not in any other types of cells, including luminal cells and fibroblasts. The positive rate of Sox10 in primary and metastatic TNBC was significantly higher than that in luminal types and human epidermal growth factor receptor 2 (HER2) overexpressed type. The sensitivity and specificity of Sox10 expression in primary TNBC and metastatic TNBC were significantly lower than GATA-3, significantly higher than FOXA1, GCDFP15, and MGB (P<0.001, P=0.0004, P=0.0064, P=0.0229, respectively). In 71 cases of primary TNBC, a higher expression rate of Sox10 was significantly associated with high-grade tumors, late-stage tumors, and tumors with involvement of four or more lymph node metastases (P=0.0145, P=0.0105, P=0.0249, respectively). CONCLUSIONS: Sox10 may be used as a novel reliable putative marker for the diagnosis of TNBC. Notably, Sox10 combined with GATA-3 expression may serve as a supplementary differential diagnostic biomarker for primary and metastatic TNBC. Besides, Sox10 may be a good predictor of the prognosis of primary and metastatic TNBC. This study also highlights the significance of targeting Sox10 as a promising potential therapeutic target gene for TNBC therapy.

Predicting perigastric lymph node metastasis in gastric cancer with CT perfusion imaging: A prospective analysis.

PURPOSE: To evaluate the diagnostic efficacy in differentiating metastatic from inflammatory perigastric lymph nodes (LNs) in patients with gastric cancer by using CT perfusion imaging (CTPI). METHOD: A total of 115 annotated perigastric LNs of 50 patients with gastric cancer confirmed by pathology underwent CTPI scan before operation. The scan data were postprocessed to acquire perfusion maps and parameters including blood flow (BF) and permeability surface (PS). A radiologist measured the short and long axis diameters, the short/long axis ratio and perfusion parameters of LNs. According to the post-operative pathology result, LNs were divided into two groups: metastatic and inflammatory nodes. Perfusion parameters and the size of LNs between two groups were respectively compared statistically, and a receiver-operating characteristic (ROC) curve analysis was used to determine the optimal diagnostic cutoff value with sensitivity, specificity and area under the curve (AUC). RESULTS: The mean values of perfusion parameters and the short/long axis diameters ratio in metastatic and inflammatory LNs, respectively, were BF of 91.64 vs. 79.35 ml/100 mg /min (p <  0.01), PS of 43.42 vs. 35.92 ml/100 mg /min (p <  0.01), and the size ratio of 0.75 vs. 0.68 (p <  0.01). The sensitivity of 85.3%, specificity of 66.0 % and AUC of 0.816 for BF with cutoff value of 80.76 ml/100 mg /min for differentiating metastatic from inflammatory nodes were higher than those of PS or the size of LNs (p < 0.05). CONCLUSIONS: BF may be a reliable diagnostic marker of metastatic perigastric LNs in gastric cancer.

An application study of CT perfusion imaging in assessing metastatic involvement of perigastric lymph nodes in patients with T1 gastric cancer.

OBJECTIVE: To assess metastatic involvement of perigastric lymph nodes (PLNs) in patients with T1 gastric cancer by using CT perfusion imaging (CTPI). METHODS: A total of 82 annotated PLNs of 33 patients with T1 gastric cancer confirmed by endoscopic ultrasonography underwent CTPI and portal phase CT scan before operation. The scan data were post-processed to acquire perfusion maps and calculate perfusion parameters including blood flow (BF) and permeability surface (PS). A radiologist measured the short axis diameters and perfusion parameters of PLNs. According to the post-operative pathology result, PLNs were divided into two groups: metastatic and inflammatory LNs. Perfusion parameters values and the size of PLNs between two groups were respectively compared statistically by t-test, and a receiver operating characteristic curve analysis was used to determine the optimal diagnostic cut-off value with sensitivity, specificity and area under the curve. RESULTS: Examined 82 PLNs were metastatic in 45 (54.9%) and inflammatory in 37 (45.1%). The mean values of perfusion parameters and the short axis diameters in metastatic and inflammatory PLNs, respectively, were BF of 97.48 vs 81.21 ml/100 mg /min (p < 0.001), PS of 45.11 vs 36.80 ml/100 mg /min (p < 0.001), and the size of 1.51 cm vs 1.29 cm (p = 0.059). The sensitivity of 84.4%, specificity of 67.6% and area under the curve of 0.826 for BF with cut-off value of 88.89 ml/100 mg /min for differentiating metastatic from inflammatory nodes were higher than those of PS or the size of PLNs (p < 0.001). CONCLUSION: CT perfusion parameters values were different between metastatic and inflammatory PLNs in T1 gastric cancer. BF value may be the most reliable diagnostic marker of metastatic PLNs, and it is helpful for clinicians to choose treatment modality or management plan in T1 gastric cancer patients. ADVANCES IN KNOWLEDGE: CTPI gives information on vascularization of LNs.BF value might be a more effective marker than PS or the size of LNs for differentiating metastatic from inflammatory LNs in patients with T1 gastric cancer.

Long Intergenic Noncoding RNA 00261 Acts as a Tumor Suppressor in Non-Small Cell Lung Cancer via Regulating miR-105/FHL1 Axis.

Purpose: Long noncoding RNAs (lncRNAs) have recently received more attention for their roles in tumor progression. LINC00261 was studied in this research to identify how it affects the progression of non-small cell lung cancer (NSCLC). Methods: Firstly, the expression of LINC00261 in NSCLC cells and paired samples of NSCLC tissue was detected by RT-qPCR. Then, the associations between LINC00261 expression level and clinicopathological characteristics were evaluated. Furthermore, functional assays of cell proliferation, colony formation and transwell, as well as western blot assay, luciferase assay and RNA immunoprecipitation (RIP) assay were conducted. Afterwards, the effects of LINC00261 expression on NSCLC formation and growing were confirmed by in vivo models. Results: As results, expression of LINC00261 was significantly down-regulated in tumor samples than that in normal samples, which was correlated with the lymphatic metastasis, tumor size, tumor stage as well as patient survival time. Knockdown of LINC00261 inhibited tumor growth and invasion ability in vitro. In addition, miR-105 was identified as a direct target of LINC00261 via mechanism experiments and its expression in tumor tissues negatively correlated to LINC00261 expression. Further experiments found that Four and expression of Half LIM domains 1 (FHL1) was negatively correlated with miR-105 but positively with LINC00261. Moreover, in vivo assays verified the overexpression of LINC00261 could suppress formation of NSCLC and regulate the expression of miR-105/FHL1 axis. Conclusions: These results indicate that LINC00261 could suppress metastasis and proliferation of NSCLC via suppressing miR-105/FHL1 axis, which may offer a new vision for interpreting the mechanism of NSCLC development.

Vestigial like family member 3 is a novel prognostic biomarker for gastric cancer.

BACKGROUND: Vestigial like family member 3 (VGLL3) is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma, but its role in gastric cancer (GC) is unclear. AIM: To explore the expression pattern and clinical significance of VGLL3 in GC. METHODS: Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE, GEPIA, and ONCOLNC databases. The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot, respectively. In addition, the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry (IHC), and the patients were accordingly classified into the high and low expression groups. The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses. RESULTS: Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues (P = 0.003), and associated with the tumor TNM stage (P = 0.0163). The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group, as per both GEPIA (P = 0.0057) and ONCOLNC (P = 0.01). The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues (P < 0.001) in a cohort of 30 GC patients. Furthermore, high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation (P < 0.05) in a cohort of 172 patients. Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group (P = 0.019). Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis. In addition, the prognostic risk model nomogram showed that VGLL3 was the most important indicator, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.613 for 3-year survival and 0.706 for 5-year survival. Finally, the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway. CONCLUSION: VGLL3 is overexpressed in GC tissues and associated with a poor prognosis, indicating its potential as a novel prognosis biomarker and therapeutic target for GC.

A pilot study of low-dose CT perfusion imaging (LDCTPI) technology in patients with triple-negative breast cancer.

PURPOSE: To investigate associations between the clinicopathologic features and CT perfusion parameters of triple-negative breast cancer (TNBC) and non-TNBC using low-dose computed tomography perfusion imaging (LDCTPI), and to find potential clinical applications in the prognosis assessment of TNBC. MATERIALS AND METHODS: A total of 60 patients with breast cancer confirmed by pathological examination were studied prospectively using LDCTPI on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using a tumor perfusion protocol in the CT perfusion software package to measure 2 parameters namely, blood flow (BF), and permeability surface (PS) area product. Patients were grouped into TNBC (n = 27) and non-TNBC (n = 33) subtypes. Associations between these two subtypes and clinicopathologic characteristics were evaluated by both univariate and multivariate logistic regression. CT perfusion parameters values were compared for clinicopathologic characteristics using independent 2-sample t test. RESULTS: TNBC displayed higher CT perfusion parameters values (BF: 57.56±10.94 vs 52.70±7.79 mL/100 g/min, p = 0.006; PS: 38.98±9.46 vs 33.39±8.07 mL/100 g/min, p = 0.001) than non-TNBC. In addition, breast cancer with poorly histologic grade or positive Ki-67 expression showed higher BF and PS values than those with well and moderately histologic grade or negative Ki-67 expression (p < 0.05). TNBC had poorer histologic grade (P = 0.032) and higher Ki-67 expression (P = 0.013) than non-TNBC. CONCLUSION: LDCTPI is a functional imaging technology from the perspective of hemodynamics with potential of clinical applications. The BF and PS values were higher in TNBC patient group than non-TNBC group. TNBC patients also have poorer clinicopathologic outcome.

BreakID: genomics breakpoints identification to detect gene fusion events using discordant pairs and split reads.

SUMMARY: Here we developed a tool called Breakpoint Identification (BreakID) to identity fusion events from targeted sequencing data. Taking discordant read pairs and split reads as supporting evidences, BreakID can identify gene fusion breakpoints at single nucleotide resolution. After validation with confirmed fusion events in cancer cell lines, we have proved that BreakID can achieve high sensitivity of 90.63% along with PPV of 100% at sequencing depth of 500× and perform better than other available fusion detection tools. We anticipate that BreakID will have an extensive popularity in the detection and analysis of fusions involved in clinical and research sequencing scenarios. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at https://github.com/SinOncology/BreakID. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Erratum to clinicopathological and theranostic analysis of 82 breast cancer patients older than 80 years.

[This corrects the article DOI: 10.21037/tcr.2017.11.24.].

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Case series and a review of the literature.

RATIONALE: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare idiopathic disease with only about 100 cases reported in the literature. PATIENT CONCERNS: Here, we presented 4 cases of DIPNECH. Four patients included 2 females and 2 males, aged 54 to 64 years old; 3 had no smoking history and 1 had history of smoking for 30 years. Surgical resection was performed for every patient. Cases 1 and 3 did not receive postoperative chemotherapy or radiotherapy, and case 2 received 4 times of postoperative chemotherapy. Case 4 just finished the operation and after a period of time, he will receive postoperative chemotherapy. DIAGNOSES: Case 1: A 57-year-old female had chest pain, and computer tomography (CT) examination prompted a mass shadow of left lung lower lobe. Case 2: A 64-year-old female had cough and expectoration for more than 1 month. CT examination showed: a lump with diameter of about 2.5 cm and irregular edge was in right lung upper lobe, being largely possibly lung cancer. Case 3: A 54-year-old male, CT examination accidentally found a long strip-shaped nodule in left lung oblique fissure when checkup's, and he had no fever, cough, expectoration, chest tightness, or chest pain. Case 4: A 61-year-old male, checkup's CT examination accidentally found a nodule, fibrosis, bronchiectasis, and secondary infection in the left lower lobe. Combined with pathological morphology and immunohistochemistry, cases 1 and 3 were diagnosed as DIPNECH with multiple carcinoid tumorlet formation and chronic inflammation and bronchiectasis, case 2 was diagnosed as an adenocarcinoma with DIPNECH and multiple carcinoid tumorlet formation, case 4 was diagnosed as an adenocarcinoma with DIPNECH and multiple carcinoid tumorlet formation and chronic inflammation and bronchiectasis. INTERVENTIONS: Surgical resection was performed for every patient. Cases 1 and 3 did not receive postoperative chemotherapy or radiotherapy, and case 2 received 4 times of postoperative chemotherapy. Case 4 just finished the operation and after a period of time, he will receive postoperative chemotherapy. OUTCOMES: Four patients have been followed up and have had good condition. LESSONS: DIPNECH is often found accidentally in a surgical specimen, is easily missed, and needs careful observation. Immunohistochemistry is necessary to make this diagnosis.