Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Preoperative CT radiomics of esophageal squamous cell carcinoma and lymph node to predict nodal disease with a high diagnostic capability.

PURPOSE: To develop CT radiomics models of resectable esophageal squamous cell carcinoma (ESCC) and lymph node (LN) to preoperatively identify LN+. MATERIALS AND METHODS: 299 consecutive patients with ESCC were enrolled in the study, 140 of whom were LN+ and 159 were LN-. Of the 299 patients, 249 (from the same hospital) were randomly divided into a training cohort (n = 174) and a test cohort (n = 75). The remaining 50 patients, from a second hospital, were assigned to an external validation cohort. In the training cohort, preoperative contrast-enhanced CT radiomics features of ESCC and LN were extracted, then integrated with clinical features to develop three models: ESCC, LN and combined. The performance of these models was assessed using area under receiver operating characteristic curve (AUC), and F-1 score, which were validated in both the test cohort and external validation cohort. RESULTS: An ESCC model was developed for the training cohort utilizing the 8 tumor radiomics features, and an LN model was constructed using 9 nodal radiomics features. A combined model was constructed using both ESCC and LN extracted features, in addition to cT stage and LN+ distribution. This combined model had the highest predictive ability among the three models in the training cohort (AUC = 0.948, F1-score = 0.878). The predictive ability was validated in both the test and external validation cohorts (AUC = 0.885 and 0.867, F1-score = 0.816 and 0.773, respectively). CONCLUSION: To preoperatively determine LN+, the combined model is superior to models of ESCC and LN alone.

A CT-based novel model to predict pathological complete response of locally advanced esophageal squamous cell carcinoma to neoadjuvant PD-1 blockade in combination with chemotherapy.

PURPOSE: To develop a novel CT-based model to predict pathological complete response (pCR) of locally advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant PD-1 blockade in combination with chemotherapy. METHODS: 117 consecutive patients with locally advanced ESCC were stratified into training cohort (n = 82) and validation cohort (n = 35). All patients underwent non-contrast and contrast-enhanced thoracic and upper abdominal CT before neoadjuvant PD-1 blockade in combination with chemotherapy (CTpre), and after two cycles of the therapy before esophagectomy (CTpost), respectively. Univariate analyses and binary logistic regression analyses of ESCC quantitative and qualitative CT features were performed to determine independent predictors of pCR. Prediction performance of the model developed with independent predictors from training cohort was evaluated by receiver operating characteristic (ROC) analysis, and validated by Kappa test in validation cohort. RESULTS: In training cohort, the difference in CT attenuation between tumor and background normal esophageal wall obtained from CTpre (ΔTNpre), tumoral increased CT attenuation after contrast-enhanced scan from CTpost images (ΔTpost) and gross tumor volume (GTV) from CTpre were independent predictors of pCR (odds ratio = 1.128 (95% confidence interval (CI): 0.997-1.277), 1.113 (95%CI: 0.965-1.239) and 1.133 (95%CI: 1.043-1.231), respectively, all P-values < 0.05). Logistic regression model equation (0.121 × ΔTNpre + 0.107 × ΔTpost + 0.125 × GTV - 9.856) to predict pCR showed the best performance with an area under the ROC of 0.876, compared with each independent predictor. The good performance was confirmed by the Kappa test (K-value = 0.796) in validation cohort. CONCLUSIONS: This novel model can be reliable to predict pCR to neoadjuvant PD-1 blockade in combination with chemotherapy in locally advanced ESCC.

Surgical Treatment for Persistent Cervical Anastomotic Fistulas With Sinus Formation.

A refractory cervical anastomotic fistula with sinus formation will seriously impede a patient's return to normal life. It is necessary to find ways to shorten the recovery time for such patients. We used a multilayered, pursestring inverted suture-embedding method for 7 patients, 6 of whom recovered; 1 patient with severe anastomotic stricture and failed. A multilayered, pursestring inverted suture-embedding method can be used to treat persistent neck anastomotic fistula with sinus formation, but it is not suitable for patients who still have a fistula to the mediastinum, thoracic cavity, or severely narrowed anastomoses.

Modified layered hand-sewn cervical end-to-side anastomosis for minimally invasive McKeown esophagectomy.

BACKGROUND: Minimally invasive McKeown esophagectomy (MIE McKeown) with cervical anastomosis is a widely used approach for the treatment of esophageal cancer (EC). Anastomotic leak is one of the most serious complications following esophagectomy. This study aimed to summarize the anastomosis procedure and assess the clinical outcomes of our modified layered hand-sewn cervical end-to-side anastomosis for cervical anastomosis during MIE McKeown. METHODS: We retrospectively reviewed clinical data of 508 consecutive EC patients who underwent MIE McKeown using the modified layered hand-sewn cervical end-to-side anastomosis between June 2016 and June 2020. RESULTS: The incidence of anastomotic leakage in our cohort was 2.0%. The postoperative stricture rate was 6.9% and the incidence of other postoperative complications was less than 9.3%. The mean time for setting up MIE McKeown was approximately 211.0 min and the average duration of postoperative hospital stay was 9.1 days. CONCLUSION: This modified layered hand-sewn cervical end-to-side anastomosis is a safe and effective method for MIE McKeown with a low incidence of anastomotic leakage, anastomotic stricture, or other postoperative complications.

Comparison of quality of life in patients with advanced Siewert type Ⅱ adenocarcinoma of the esophagogastric junction treated by three different operations / 中国胸心血管外科临床杂志

@#Objective     To compare the quality of life (QOL) of advanced Siewert type Ⅱ adenocarcinoma esophagogastric junction (AEG) patients treated by the total gastrectomy, traditional proximal gastrectomy or proximal gastrectomy with gastric tube reconstruction opertations, and to provide some clinical basis for the choice of surgical methods for AEG. Methods     A total of 90 patients with Siewert type Ⅱ AEG were retrospectively collected from the Affiliated Hospital of North Sichuan Medical College. Patients were divided into 3 groups according to different surgical methods (n=30 in each group), a total gastrectomy group (23 males, 7 females, aged 47-79 years), a traditional proximal gastrectomy group (treated with the traditional proximal gastrectomy procedure, 19 males, 11 females, aged 44-80 years), and a narrow gastric tube group (treated with the proximal gastrectomy with gastric tube reconstruction procedure, 25 males, 5 females, aged 47-83 years). The Chinese version of Quality of Life Questionnaire Core-30 (QLQ-C30) and Quality of Life Questionnaire Oesophagogastric-25 (QLQ-OG25) designed by European Organization for Research and Treatment of Cancer (EORTC) were used to collect the patients’ information in the three groups about their QOL during the first six months and one year after the three procedures. Results     There was no statistical difference in the clinical data among the three groups (all P>0.05). QOL during the first six months after the operations assessed by the QLQ-C30 questionnaire table showed that the narrow gastric tube group was significantly best in total QOL, physical function, fatigue, and emotional function among the three groups (all P<0.05). The total gastrectomy group was the worst in role function, dyspnea, fatigue and diarrhea among the three groups (all P<0.05). The traditional proximal gastrectomy group had a worse evaluation in lose of appetite than the other two groups (P<0.05). QOL during the first six months after the operations assessed by the QLQ-OG25 questionnaire table showed that the traditional proximal gastrectomy group had a significantly worse evaluation in palirrhea than the other two groups (both P<0.05). The total gastrectomy group had a significantly worse evaluation in anxiety than the other two groups (both P<0.05). QOL during the first year after the operations assessed by the QLQ-C30 questionnaire table showed that the narrow gastric tube group had a significantly highest evaluation in total QOL physical function and emotional function among the three groups (all P<0.05). The total gastrectomy group had a significantly worst evaluation in diarrhea among the three groups (P<0.05). QOL during the first year after operations assessed by QLQ-OG25 questionnaire table showed that the traditional proximal gastrectomy group had a significantly worse evaluation in palirrhea than the other two groups (all P<0.05). Conclusion     The narrow tubular esophagogastric anastomosis is better than the total gastrectomy and the traditional proximal gastrectomy for the treatment of the advanced Siewert type Ⅱ adenocarcinoma of esophagogastric junction, so this operation is worth being recommended.

Author Correction: Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

To compare the differences in dietary status and knowledge of esophageal cancer (EC) between residents of high- and low-incidence areas. We investigated dietary conditions and EC knowledge among residents in high- and low-EC incidence areas (Yanting and Qingzhen counties). Residents in Yanting consumed more pickled vegetables, salted meat and barbecued food (P < 0.05). Analysis of the past ten-year trend in Yanting consumed fresh vegetables/fruits, beans, sauerkraut, hot food, and barbecued food had gradually increased, and the trend was less than that in Qingzhen County. However, the gradual increasing trend in consumption of pickled vegetables, pickled meat, and spicy food over the past 10 years was greater (P < 0.05). Drinking water in Yanting County was healthier than that in Qingzhen County (P < 0.05). In terms of EC knowledge, the proportions of residents in Yanting who had a clear understanding, knowledge or had heard of EC or knew the common causes, primary symptoms, therapeutic measures, preventive measures, and government interventions for EC were all higher than in Qingzhen (P < 0.05). Residents in Yanting had greater EC knowledge but more harmful dietary habits than those in Qingzhen.

Multiple intracranial metastases from postoperative giant sarcomatoid malignant pleural mesothelioma: A case report and literature review.

Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare tumor with poor response to treatment and a dismal prognosis. Distant metastases are not uncommon and usually appear at the late stages of the disease. However, cerebral metastases have rarely been documented. We herein report a case of a giant sarcomatoid carcinoma of the pleura in a 41-year-old male patient with no history of exposure to asbestos, who presented with a chief complaint of left-sided chest pain for 1 month. Extrapleural pneumonectomy and rib excision were performed. At 5 months after the surgery, the patient was diagnosed with multiple intracranial metastatic neoplasms and succumbed to the disease soon thereafter. The aim of the present case report was to emphasize this rare metastatic pattern and aggressive clinical course of SMPM, with a supplementary review of the previously published literature.

Associations between the expression of MTA1 and VEGF-C in esophageal squamous cell carcinoma with lymph angiogenesis and lymph node metastasis.

The aim of the present study was to investigate the association between the expression levels of metastasis-related gene 1 (MTA1) and vascular endothelial growth factor C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) with lymph angiogenesis and lymph node metastasis. The paraffin-embedded tissue samples of 107 cases of ESCC and 56 cases of normal esophageal tissues were collected from the Department of Cardiothoracic Surgery, Suining Central Hospital from March 2013 to January 2014. Immunohistochemical assays were performed to detect the expression levels of MTA1, VEGF-C and D2-40 in ESCC, and the micro-lymphatic vessel density (LVD) was evaluated. Their associations with various clinicopathological parameters were also analyzed. The protein expression levels of MTA1 and VEGF-C in ESCC were significantly higher compared with those in normal esophageal tissues (P<0.05); the high protein expression levels of MTA1 and VEGF-C in ESCC tissues at various tumor-node-metastasis stages exhibited statistically significant differences, as revealed by the Kruskal-Wallis test (P<0.05). The protein expression levels of MTA1 and VEGF-C in ESCC exhibited positive correlations (Spearman's ρ, r=0.512; P=0.000); the LVD level in the group with high expression of MTA1 and VEGF-C was significantly higher compared with in the low expression group (P<0.05). The comparison between MTA1 and VEGF-C protein expression levels in the group with a high rate of lymph node metastasis demonstrated statistically significant differences when compared with in the low lymph node metastasis group (P<0.05). The expression levels of MTA1 and VEGF-C in ESCC exhibited a positive correlation in ESCC, which may co-promote lymph angiogenesis and lymph node metastasis in ESCC; therefore, they may be used as biomarkers for determining the prognosis of ESCC.

Pulmonary chondroma: A clinicopathological study of 29 cases and a review of the literature.

The present retrospective study was designed to review the clinicopathological features and outcome of surgical treatment of pulmonary chondroma, and to accumulate data for the clinical diagnosis and therapy. The clinicopathological data from 29 patients, aged between 38- and 78-years-old, with pulmonary chondroma who underwent surgical operation between July 2003 and June 2015 were reviewed. Of these patients, 18 exhibited no clinical symptoms, 7 were characterized by coughing, hemoptysis, shortness of breath and other symptoms and only 3 patients exhibited chest pain as the predominant symptom. The average size of the neoplasms was 3.6 cm. All patients were pathologically diagnosed. Operative time was 126±22 min, the mean intraoperative blood loss was 82±23 ml and the drainage duration was 3.1±1.8 days. A total of 6 postoperative complications were noted. The patients were followed-up for 2-135 months. A total of 23 patients were alive without recurrence, 4 patients succumbed to mortality, 2 patients were lost at follow-up. Pulmonary chondroma is a rare benign tumor of the lung. The clinical symptoms were concealed and often misdiagnosed as a tuberculosis tumor, hamartoma, peripheral lung cancer or a single metastatic tumor. Complete resection was the best treatment providing patients with a good prognosis. After definite diagnosis, it is necessary to exclude Carney's triad.

Comparative study of self-expanding metal stent and intraluminal radioactive stent for inoperable esophageal squamous cell carcinoma.

BACKGROUND: We compared the effectiveness of self-expanding metal stent alone vs. radioactive stent embedded with 125I seeds implantation insertion in patients of inoperable esophageal squamous cell cancer combined with malignant esophageal stenosis. METHODS: We studied two groups of patients with stenosis attribute to inoperable esophageal squamous cell carcinoma. Group A had placed self-expanding metal stent alone insertion; group B encountered radioactive stent embedded with 125I seeds. Patients were followed up by monthly home visits or telephone interview. Survival time was analyzed with Kaplan-Meier analysis. Log rank test was used to analyze factors of survival time for all significant differences. RESULTS: There was no significant difference between the two groups of all baseline characteristics. There was no statistical difference in complications including massive hematemesis, pain more than 1 month, stent migration, and restenosis. Survival time and causes of death such as tumor metastasis, massive hemorrhage, non-tumor-related factors, and restenosis were comparable between the two groups (P>0.05). The medical costs were significantly less in group A than those in group B (P<0.01). CONCLUSIONS: Radioactive stent embedded with (125)I seeds was not significant in improving survival rate, but showed to increase hospitalization costs compared to self-expandable metal stent alone in treating inoperable esophageal squamous cell carcinoma stricture.

A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay).

PURPOSE: To develop an assay to quantify serum immunoglobulin (IgG, IgM, IgA) levels using dried blood spots (DBS) obtained on collection cards to be used as a tool for targeted screening for hypogammaglobulinemia. METHODS: DBS samples, along with simultaneous serum samples, were collected from 107 healthy individuals (11 months to 57 years of age). After eluting proteins from DBS, IgG, IgM, and IgA were quantified by an enzyme-linked immunosorbent assay (ELISA). The Ig-DBS assay was validated through calibration curve performance, intra- and inter-assay precision, accuracy, specificity, selectivity, and linearity. The ELISA measurements were compared with serum Ig levels obtained using a standard nephelometry assay on serum samples collected simultaneously with the DBS samples and the results of the two assays were correlated. The stability of IgG, IgM, and IgA in the DBS was tested at room temperature, 36° to 38 °C, 2 to 8 °C, and -25 to -40 °C, from 4 to 14 days. RESULTS: The Ig-DBS assay demonstrated precision, accuracy, specificity, selectivity, and linearity. Using the identified correlation coefficients of 0.834 for IgG, 0.789 for IgM, and 0.918 for IgA, the standard nephelometry-based normal reference ranges for all 3 serum Ig isotypes could be used with the Ig-DBS assay in individuals ≥16 years of age. The DBS samples were stable for 14 days at room temperature in a closed polyethylene bag. CONCLUSIONS: The Ig-DBS assay is both sensitive and accurate for quantification of serum immunoglobulins. Samples are sufficiently stable at ambient temperature to allow for convenient shipping and analysis at a centralized laboratory. This assay therefore presents a new option for screening patients ≥16 years of age for hypogammaglobulinemia in any setting.

Anatomic variation of the common palmar digital nerves and arteries.

Variations in the course and distribution of common palmar digital nerves and arteries are rare. A classic common palmar digital nerves and arteries are defined as concomitant. During routine dissection classes to undergraduate medical students we observed formation of each common palmar digital nerve divided into 2 or 3 branches and formed a ring enclosing the corresponding common palmar digital artery. Knowledge of the anatomical variations of the common palmar digital nerves and arteries is crucial for safe and successful hand surgery.

Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma.

Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvß3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.

Rationale and preclinical efficacy of a novel anti-EMP2 antibody for the treatment of invasive breast cancer.

Despite significant advances in biology and medicine, the incidence and mortality due to breast cancer worldwide is still unacceptably high. Thus, there is an urgent need to discover new molecular targets. In this article, we show evidence for a novel target in human breast cancer, the tetraspan protein epithelial membrane protein-2 (EMP2). Using tissue tumor arrays, protein expression of EMP2 was measured and found to be minimal in normal mammary tissue, but it was upregulated in 63% of invasive breast cancer tumors and in 73% of triple-negative tumors tested. To test the hypothesis that EMP2 may be a suitable target for therapy, we constructed a fully human immunoglobulin G1 (IgG1) antibody specific for a conserved domain of human and murine EMP2. Treatment of breast cancer cells with the anti-EMP2 IgG1 significantly inhibited EMP2-mediated signaling, blocked FAK/Src signaling, inhibited invasion, and promoted apoptosis in vitro. In both human xenograft and syngeneic metastatic tumor monotherapy models, anti-EMP2 IgG1 retarded tumor growth without detectable systemic toxicity. This antitumor effect was, in part, attributable to a potent antibody-dependent cell-mediated cytotoxicity response as well as direct cytotoxicity induced by the monoclonal antibody. Together, these results identify EMP2 as a novel therapeutic target for invasive breast cancer.

[Evaluation of the value of 7th editions of UICC-AJCC esophageal and gastric cancer TNM staging systems for prognostic prediction of adenocarcinoma of esophagogastric junction (Siewert type II)].

OBJECTIVE: To compare the value of applicability of the 7th edition of UICC-AJCC esophageal and gastric cancer TNM staging system in the prognostic prediction of adenocarcinoma of esophagogastric junction (EGJ). METHODS: During June 1, 2007 through Dec. 31, 2010, a total of 199 patients with adenocarcinoma of esophagogastric junction (Siewert type II) underwent R0-intent resection from June 1, 2007 to Dec 31, 2010 in our hospital. Their clinicopathological and survival data were retrospectively analyzed with Kaplan-Meier and Cox regression models. They were restaged according to the 7th edition of UICC/AJCC TNM stage systems for esophageal adenocarcinoma and gastric cancer, respectively. Then the likelihood ratio chi-square test related to the Cox regression model and Akaike information criterion (AIC) were used for measuring goodness of fit for both staging systems. RESULTS: 199 patients with Siewert type II esophagogastric junction adenocarcinoma were identified in this study. Out of them, there were 162 males and 37 females. Their age range was from 38 to 79 years, with a median age of 62 years. 176 cases underwent transthoracic surgery, and other 23 cases underwent transabdominal surgery. TNM-EC and TNM-GC classified 4 patients to stage T1, 39 to T2, 139 to T3, and 17 to T4a, respectively, and classified 76 patients to stage N0, 58 to N1, 49 to N2, 16 to N3, respectively. The median follow-up period was 30 months. The 1-, 3-, and 5-year survival rates were 95.0%, 52.7% and 39.2%, respectively. Univariate analysis indicated that age at surgery (P = 0.009), surgical approach (P = 0.002), cell differentiation (P = 0.030), preoperative co-morbidity implications (P = 0.026), depth of tumor invasion (P < 0.001) and number of metastatic lymph nodes (P < 0.001) were significantly influencing factors of postoperative overall survival. Multivariate analysis showed that the independent prognostic factors for adenocarcinoma of esophagogastric junction were only T stage, N stage and preoperative co-morbidity and morbidities according to the 7th edition of esophageal cancer or gastric cancer TNM staging systems. The AIC value was 961.4 for the 7th edition of esophageal adenocarcinoma caner staging system, and 965.7 for the 7th edition of gastric cancer staging system. CONCLUSIONS: The UICC/AJCC 7th edition of esophageal adenocarcinoma cancer TNM classification staging system is superior to the 7th edition of gastric cancer TNM staging system for adenocarcinoma of esophagogastric junction.

Overexpression of ECRG4 enhances chemosensitivity to 5-fluorouracil in the human gastric cancer SGC-7901 cell line.

The aim of this study was to examine the effects of esophageal cancer-related gene 4 (ECRG4) expression levels on chemotherapeutic sensitivity of gastric cancer cells. A SGC-7901 cell system with tetracycline-inducible ECRG4 expression (SGC-7901/ECRG4) was successfully established. ECRG4 mRNA and protein expression levels were detected using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Chemosensitivity to 5-fluorouracil (5-FU) was examined by cell proliferation assay and cell apoptosis assay. ECRG4 mRNA and protein expression levels were significantly upregulated in SGC-7901/ECRG4 cells induced with tetracycline. Compared with control cells, the growth inhibition rate of cells with ECRG4 overexpression was significantly increased when treated with 5-FU. Treatment with 5 µmol/l 5-FU resulted in 15.2 % apoptotic cells, whereas such treatment after overexpression of ECRG4 resulted in 44.5 % apoptotic cells. In conclusion, overexpression of ECRG4 enhanced the chemosensitivity of gastric cancer SGC-7901 cells to 5-FU through induction of apoptosis.

High COL4A3 expression correlates with poor prognosis after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer.

In this study, we investigated whether COL4A3 mRNA expression levels were associated with clinical outcomes after treatment with a combination of gemcitabine (Gem)/cis-diamminedichloroplatinum(II) (CDDP) regimen for patients with advanced stage non-small cell lung cancer (NSCLC). Response and survival were correlated with the level of COL4A3 expression in 58 patients with advanced (stage IIIb or IV) NSCLC treated as part of a multicenter randomized trial with Gem 1,250 mg/m(2) on days 1 and 8 plus CDDP 100 mg/m(2) on day 1 every 3 weeks. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens, and relative expression levels of COL4A3/ß-actin were measured using a quantitative reverse transcription-PCR (Taqman) system. COL4A3 expression was detectable in all tumors. There were no significant differences in COL4A3 levels by gender, age, performance status, weight loss, or tumor stage. The overall response rate was 45.8 %. There were no significant associations between COL4A3 expression and response. Median overall survival was significantly longer in patients with low COL4A3 expression tumors compared to patients with high expression tumors. COL4A3 expression, Eastern Cooperative Oncology Group performance status, and presence of weight loss were significant prognostic factors for survival in a Cox proportional hazards multivariable analysis. These data suggest that COL4A3 expression is a predictive factor for survival after CDDP/Gem therapy in advanced NSCLC. Although there was a trend toward decreased response with high COL4A3 mRNA levels, this difference failed to reach statistical significance. This result may reflect the impact of Gem and the requirement for COL4A3 expression for CDDP/Gem synergism or may be attributable to the relatively small patient sample size in this study. Prospective studies of COL4A3 as a predictive marker for activity of CDDP-based regimens in NSCLC are warranted.