Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis

Objective： Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis. The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis. Methods： Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer （CT≥2M0）. We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy, and examined the relationship between peritoneal dissemination （P） and cytology results （CY）. Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis. Multivariate logistic regression analysis and receiver-operator characteristic （ROC） analysis were performed in training set to find out risk factors ofintra-abdominal metastasis, and then validate it in testing set. Results： Out of 249 cM0 patients, 51 （20.5%） patients with intra-abdominal metastasis were identified by diagnostic laparoscopy, including 20 （8.0%） P1CY1, 17 （6.8%） POCY1 and 14 （5.6%） P1CY0 patients. In the training set, multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography （CT） scan ≥21 mm and tumor-occupied 〉2 portions of stomach are predictive factors of metastasis. In the testing set, when diagnostic laparoscopy was performed on patients who had one or two of these risk factors, the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0% and 32.1%, respectively. Conclusions： According to our results, depth of tumor invasion and tumor-occupied portions of stomach are predictive factors ofintra-abdominal metastasis.

Dual effect of WISP-1 in diverse pathological processes

Wnt-1 inducible signaling pathway-1（WISP-1）, also known as CCN-4, belongs to the connective tissue growth factor（CTGF） family. WISP-1 is primarily expressed in embryonic stem cells and is involved in adult organ development. WISP-1 participates in many cellular processes, including proliferation, differentiation, apoptosis and adhesion. In addition, WISP-1 plays an important role in diverse pathophysiological processes, such as embryonic development, inflammation, injury repairs and cancers. Recent studies showed that WISP-1 was highly correlated with tumor progression and malignant transformation, whereas it played an oncogenic role in colorectal cancer,cholangiocarcinoma, hepatocellular carcinoma and breast cancer. However, interestingly, WISP-1 exerts a tumorsuppressing role in lung and prostate cancers. WISP-1 promotes cell proliferation, adhesion, motility, invasion,metastasis and epithelial-to-mesenchymal transition via particular signaling pathways. In this review, we discussed the structure, expression profile, functions, clinical significance and potential mechanisms of WISP-1 in cancer and non-neoplastic diseases.

MAGI1 inhibits migration and invasion via blocking MAPK/ERK signaling pathway in gastric cancer

Objective： To explore the association of membrane-associated guanylate kinase inverted 1（MAGI1） with gastric cancer（GC） and the related molecular mechanisms.Methods： The reverse transcription-polymerase chain reaction（RT-PCR） and immunohistochemistry（IHC）were utilized to measure the MAGI1 expression level in GC tissues. Quantitative real-time PCR and Western blotting were used to ensure the MAGI1 expression in GC cell lines. Small hairpin RNA（sh RNA） was applied for knockdown of endogenous MAGI1 in GC cells. MTT assay and colony formation assay, scratch wounding migration assay and transwell chamber migration assay, as well as transwell chamber invasion assay were employed respectively to investigate the GC cell proliferation, migration and invasion in MAGI1-knockdown and control GC cells. The potential molecular mechanism mediated by MAGI1 was studied using Western blotting and RT- PCR.Results： RT-PCR and IHC verified MAGI1 was frequently expressed in matched adjacent noncancerous mucosa compared with GC tissues and the expression of MAGI1 was related to clinical pathological parameters. Functional assays indicated that MAGI1 knockdown significantly promoted GC cell migration and invasion. Further mechanism investigation demonstrated that one pathway of MAGI1 inhibiting migration and invasion was mainly by altering the expression of matrix metalloproteinases（MMPs） and epithelial-mesenchymal transition（EMT）-related molecules via inhibiting MAPK/ERK signaling pathway.Conclusions： MAGI1 was associated with GC clinical pathological parameters and acted as a tumor suppressor via inhibiting of MAPK/ERK signaling pathway in GC.

Germline mutations in hereditary diffuse gastric cancer

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Among which, about 1%–3% of gastric cancer patients were characterized by inherited gastric cancer predisposition syndromes, knowing as hereditary diffuse gastric cancer（HDGC）. Studies reported that CDH1 germline mutations are the main cause of HDGC. With the help of rapid development of genetic testing technologies and data analysis tools, more and more researchers focus on seeking candidate susceptibility genes for hereditary cancer syndromes. In addition, National Comprehensive Cancer Network（NCCN） guidelines recommend that the patients of HDGC carrying CDH1 mutations should undergo prophylactic gastrectomy or routine endoscopic surveillances. Therefore, genetic counseling plays a key role in helping individuals with pathogenic mutations make appropriate risk management plans. Moreover, experienced and professional genetic counselors as well as a systematic multidisciplinary team（MDT） are also required to facilitate the development of genetic counseling and benefit pathogenic mutation carriers who are in need of regular and standardized risk management solutions. In this review, we provided an overview about the germline mutations of several genes identified in HDGC, suggesting that these genes may potentially act as susceptibility genes for this malignant cancer syndrome. Furthermore, we introduced information for prevention, diagnosis and risk management of HDGC. Investigations on key factors that may have effect on risk management decision-making and genetic data collection of more cancer syndrome family pedigrees are required for the development of HDGC therapeutic strategies.

TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance

Immune checkpoint blockade(ICB)offers a new opportunity for treatment for gastric cancer(G.C.).Understanding the upstream regulation of immune checkpoints is crucial to further improve the efficacy of ICB therapy.Herein,using the CRISPR-Cas9-based genome-wide screening,we identified TRIM28 as one of the most significant regulators of PD-L1,a checkpoint protein,in G.C.cells.