Clinical application of combined detection of SARS-CoV-2-specific antibody and nucleic acid.

BACKGROUND: The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM: To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS: We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS: Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups (P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION: Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

Eukaryotic initiation factor 5A2 and human digestive system neoplasms.

Eukaryotic initiation factor 5A2 (eIF5A2), as one of the two isoforms in the family, is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer. Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers. Accumulated evidence shows that eIF5A2 initiates tumor formation, enhances cancer cell growth, increases cancer cell metastasis, and promotes treatment resistance through multiple means, including inducing epithelial-mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Expression of eIF5A2 in cancer correlates with poor survival, advanced disease stage, as well as metastasis, suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target. This review focuses on the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in cancer, especially in human digestive system neoplasms.

Factors associated with early recurrence after curative surgery for gastric cancer.

AIM: To characterize patterns of gastric cancer recurrence and patient survival and to identify predictors of early recurrence after surgery. METHODS: Clinicopathological data for 417 consecutive patients who underwent curative resection for gastric cancer were retrospectively analyzed. Tumor and node status was reclassified according to the 7(th) edition of the American Joint Committee on Cancer tumor-node-metastasis classification for carcinoma of the stomach. Survival data came from both the patients' follow-up records and telephone follow-ups. Recurrent gastric cancer was diagnosed based on clinical imaging, gastroscopy with biopsy, and/or cytological examination of ascites, or intraoperative findings in patients who underwent reoperation. Predictors of early recurrence were compared in patients with pT1 and pT2-4a stage tumors. Pearson's χ (2) test and Fisher's exact test were used to compare differences between categorical variables. Survival curves were constructed using the Kaplan-Meier method and compared via the log-rank test. Variables identified as potentially important for early recurrence using univariate analysis were determined by multivariate logistic regression analysis. RESULTS: Of 417 gastric cancer patients, 80 (19.2%) were diagnosed with early gastric cancer and the remaining 337 (80.8%) were diagnosed with locally advanced gastric cancer. After a median follow-up period of 56 mo, 194 patients (46.5%) experienced recurrence. The mean time from curative surgery to recurrence in these 194 patients was 24 ± 18 mo (range, 1-84 mo). Additionally, of these 194 patients, 129 (66.5%) experienced recurrence within 2 years after surgery. There was no significant difference in recurrence patterns between early and late recurrence (P < 0.05 each). For pT1 stage gastric cancer, tumor size (P = 0.011) and pN stage (P = 0.048) were associated with early recurrence of gastric tumors. Patient age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage gastric cancer (P < 0.05 each). CONCLUSION: Age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy are independent factors influencing early recurrence of pT2-4a stage gastric cancer.

Overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) correlates with cell aggressiveness and poor survival in gastric cancer.

Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer.

[Effects of eukaryotic translation initiation factor 5A2 down-regulation by small interfering RNA on aggressiveness of MKN28 human].

OBJECTIVE: To investigate the effects of eukaryotic translation initiation factor 5A2 (EIF5A2) down-regulation by small interfering RNA (siRNA) on aggressiveness of human gastric cancer cell and its potential mechanisms. METHODS: The expressions of EIF5A2 in human gastric cancer cell lines (MKN28 and HGC27) and immortalized gastric mucosal epithelial cells (GES-1) were measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. EIF5A2 gene in MKN28 cells was silenced by RNA interference and the inhibitory effect was evaluated by both qRT-PCR and Western blotting. Cell proliferation was assessed by CCK-8 assay. Cell migration and invasion were assessed by Transwell assay. The possible downstream targets of EIF5A2, such as CyclinD1, CyclinD3, matrix metallopeptidase-9 (MMP-9), E-cadherin, vimintin, C-myc, and metastasis-associated protein 1 (MTA1) expression levels, were examined by Western blotting. RESULTS: High expressions of EIF5A2 were found in MKN28 cells and human gastric adenocarcinoma tissues. Both EIF5A2 mRNA and protein expression in MKN28 cells were significantly down-regulated by siRNA#1 and siRNA#2, especially siRNA#1. Knockdown of EIF5A2 caused an apparent suppression of MKN28 cell proliferation (all P<0.01), migration (P<0.001), and invasion (P<0.001). After the knockdown of EIF5A2 in MKN28 cells, E-cadherin levels were upregulated, whereas vimentin, Cyclin D1, Cyclin D3, C-myc and MTA1 levels were downregulated. CONCLUSION: Knockdown of EIF5A2 may inhibit MKN28 cell proliferation by downregulating the CyclinD1 and CyclinD3 and suppressing the cell migration and invasion by inhibiting MTA1, C-myc and epithelial-mesenchymal transition.

Laparoscopic-endoscopic cooperative surgery for gastric submucosal tumors.

AIM: To assess the feasibility, safety, and advantages of minimally invasive laparoscopic-endoscopic cooperative surgery (LECS) for gastric submucosal tumors (SMT). METHODS: We retrospectively analyzed 101 consecutive patients, who had undergone partial, proximal, or distal gastrectomy using LECS for gastric SMT at Peking Union Medical College Hospital from June 2006 to April 2013. All patients were followed up by visit or telephone. Clinical data, surgical approach, pathological features such as the size, location, and pathological type of each tumor; and follow-up results were analyzed. The feasibility, safety and effectiveness of LECS for gastric SMT were evaluated, especially for patients with tumors located near the cardia or pylorus. RESULTS: The 101 patients included 43 (42.6%) men and 58 (57.4%) women, with mean age of 51.2 ± 13.1 years (range, 14-76 years). The most common symptom was belching. Almost all (n = 97) patients underwent surgery with preservation of the cardia and pylorus, with the other four patients undergoing proximal or distal gastrectomy. The mean distance from the lesion to the cardia or pylorus was 3.4 ± 1.3 cm, and the minimum distance from the tumor edge to the cardia was 1.5 cm. Tumor pathology included gastrointestinal stromal tumor in 78 patients, leiomyoma in 13, carcinoid tumors in three, ectopic pancreas in three, lipoma in two, glomus tumor in one, and inflammatory pseudotumor in one. Tumor size ranged from 1 to 8.2 cm, with 65 (64.4%) lesions < 2 cm, 32 (31.7%) > 2 cm, and four > 5 cm. Sixty-six lesions (65.3%) were located in the fundus, 21 (20.8%) in the body, 10 (9.9%) in the antrum, three (3.0%) in the cardia, and one (1.0%) in the pylorus. During a median follow-up of 28 mo (range, 1-69 mo), none of these patients experienced recurrence or metastasis. The three patients who underwent proximal gastrectomy experienced symptoms of regurgitation and belching. CONCLUSION: Laparoscopic-endoscopic cooperative surgery is feasible and safe for patients with gastric submucosal tumor. Endoscopic intraoperative localization and support can help preserve the cardia and pylorus during surgery.

Benefits of intra-operative systemic chemotherapy during curative surgery in patients with locally advanced gastric cancer.

BACKGROUND: There is little information on the impact of intra-operative systemic chemotherapy on gastric cancer. The aim of this study was to identify prognostic factors in patients with locally advanced gastric cancer and undergoing curative resection, with a focus on evaluating survival benefits and tolerance of intra-operative systemic chemotherapy. METHODS: We retrospectively analyzed clinicopathological data for 264 consecutive patients who underwent curative resection for gastric cancer at Peking Union Medical College Hospital from January 2002 to January 2007. Survival curves were plotted using the Kaplan-Meier method and compared using log-rank tests. Univariate and multivariate analyses were performed with the Cox proportional hazard model. RESULTS: Patients who received intra-operative systemic chemotherapy had higher 5-year overall survival and 5-year disease-free survival rates (P = 0.019 and 0.010, respectively) than patients who did not receive intra-operative systemic chemotherapy. In the subgroup analysis, systemic intra-operative chemotherapy benefited the 5-year overall survival and disease-free survival rates for patients with cancer of stage pTNM IB-IIIB, but not stage pTNM IIIC. Patients who received intra-operative systemic chemotherapy in combination with post-operative chemotherapy had higher 5-year overall survival and 5-year disease-free survival rates (P = 0.046 and 0.021, respectively) than patients who only received postoperative chemotherapy. However, the difference in these rates between patients who received only intra-operative systemic chemotherapy and patients who only received curative surgery was not statistically significant (P = 0.150 and 0.170, respectively). Multivariate analyses showed that intra-operative systemic chemotherapy was a favorable prognostic factor for the overall survival and disease-free survival rates (P = 0.048 and 0.023, respectively). No grade 4 toxicities related to intra-operative systemic chemotherapy were recorded within the 4 weeks after surgery. CONCLUSION: Intra-operative systemic chemotherapy during curative surgery may benefit patients with stage pTNM IBIIIB gastric cancer in terms of both overall survival and disease-free survival.

[Research advances in molecular pathogenesis of thyroid cancer].

Thyroid cancer is the one of the most common endocrine tumors. The biological behaviors and prognoses of the thyroid cancer of different histological types remarkably differ. The highly invasive thyroid cancer responds poorly to traditional therapies. Recent research advances in the molecular mechanisms of the pathogenesis of thyroid cancer have revealed the roles of many genetic and epigenetic variations such as gene mutation, abnormal gene amplification, and abnormal gene methylation in the development of thyroid cancer, which provides new insights in the molecular diagnosis, prognosis, and target therapy of the thyroid cancer.

[Effect of enteral nutrition via jejunostomy catheter on quality of life in gastric cancer patients who have undergone gastrectomy].

OBJECTIVE: To study the effect of enteral nutrition via jejunostomy catheter on the quality of life in gastric cancer patients who have undergone gastrectomy. METHODS: We retrospectively analyzed clinical data of 104 consecutive patients who had undergone curative resection for gastric cancer in Peking Union Medical College Hospital in 2011.All data were obtained from a prospectively maintained database of gastric cancer.The quality of life was compared between jejunostomy tube group(n=49)and tube-free group(n=55). RESULTS: The two groups were matched in gender,age,tumor size,tumor location,histological type,pTNM stage,type of surgery,body mass index(BMI),quality of life scales,and cycles of postoperative adjuvant chemotherapy(all P>0.05).Also,the global health status(P=0.154),physical function score(P=0.321),role function score(P=0.492),and fatigue symptom score(P=0.845)were not significantly different between these two groups one month after surgery.Three and 6 months after the surgery,patients in the jejunostomy tube group had significantly higher overall health status scores( P<0.001,P=0.038),physical function scores(P=0.004,P=0.005),and role function scores(P=0.002,P=0.038)and significantly lower fatigue symptom scores(P=0.020,P=0.043)when compared to patients from tube-free group. CONCLUSION: Enteral nutrition via jejunostomy catheter can improve the quality of life of gastric cancer patients who have undergone gastrectomy.

Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway.

Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NFκB signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NFκB signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NFκB signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.

[Expression of doublecortin-like kinase 1 in human gastric cancer and its correlation with prognosis].

OBJECTIVE: To investigate the expression of doublecortin-like kinase 1(DCLK1)in gastric cancer and its prognostic significance. METHODS: The expression of DCLK1 was examined by immunohistochemical staining of paraffin-embedded tumor specimens from 122 patients who underwent curative gastrectomy for gastric cancer at Peking Union Medical College Hospital between July 2002 and December 2006. Survival curves were described by the Kaplan-Meier method and compared by the Log-rank test. Univariate and multivariate analysis was performed with the Cox proportional hazard model. RESULTS: The expression of DCLK1 in tumor cells was significantly upregulated in 51 of 122 patients. High expression of DCLK1 in tumor cells was strongly correlated with pN stage(P=0.029)and lymphovascular invasion(P=0.029). Kaplan-Meier analysis revealed that patients with DCLK1 high expression had a significantly lower 5-year overall survival(OS)rate than that of patients with DCLK1 low expression(39. 0% vs. 65. 8%, P=0.001), as well as a significantly lower 5-year disease-free survival(DFS)rate(37. 0% vs. 64. 5%, P=0.001). Univariate and multivariate analyses showed that DCLK1 expression(both P=0.036)was an independent factor for predicting OS and DFS rate. CONCLUSIONS: High expression of DCLK1 in gastric cancer cells is associated with pN stage and lymphovascular invasion. It may be a predictor for poor survival in patients undergoing surgery for gastric cancer.