Background: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. Methods: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. Results: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. Conclusions: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. Trial registration: ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

The multidisciplinary team (MDT) discussion has earned increasing popularity for the delivery of cancer care. However, MDT meeting (MDTM) is time and resource intensive, and some efforts to optimize discussion processes are required. This study aims to investigate the efficiency of electronic list-based MDTM in treatment of gastrointestinal (GI) malignancy. Between January 2015 and December 2016, patients with GI cancers were retrospectively reviewed. Patients permitting an MDTM with our novel technique (eMDT group) were compared with those undergoing a traditional discussion (cMDT group). The efficiency of MDT working, including time cost per meeting or case and overall number of reviewed cases, was checked, with accuracy of clinical staging and other outcomes explored meanwhile. Three thousand six hundred seventy-four patients were included, with 2156 (58.7%) and 1518 (41.3%) cases for eMDT and cMDT groups, respectively. Comparisons in age (P = 0.529), gender (P = 0.844), cancer type (P = 0.218), treatment plan (P = 0.737), and pathological stage (P = 0.098) were not significant between groups. However, the average time cost in both each meeting (149.4 vs. 205.1 min; P < 0.001) and each case (3.1 vs. 6.2 min; P < 0.001) was markedly reduced. Besides, this novel technique was associated with improved accuracy of clinical staging (P = 0.070) and reduced hospital stay (P < 0.001) compared with the traditional approach, with similar incidence of complications observed (P = 0.243). The MDT working based on an intelligent checklist could save considerable time while not affecting treatment of GI malignancies. The improved efficiency also earns an increased capacity of hospital admission and in-patient care.