Chemoresistance is a major cause of treatment failure and high mortality in advanced gastric cancer (AGC). Currently, the mechanism of chemoresistance remains unclear, and there is no biomarker to accurately predict the efficacy of chemotherapy. In the present study, we established human gastric cancer (GC) cell lines resistant to 5-fluorouracil (5FU), paclitaxel (TA), or cisplatin (DDP) by gradient drug treatment and generated a novel monoclonal antibody 5B2 targeting heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) overexpressed in chemoresistant GC cells. Overexpressing HNRNPC in GC cells promoted chemoresistance, and knockdown of HNRNPC by small interfering RNA (siRNA) reversed chemoresistance. By utilizing available datasets, we demonstrated that high level of HNRNPC transcript indicated poor overall survival (OS) and free of progression (FP). HNRNPC expression was negatively correlated with OS of GC patients treated with 5FU-based drugs and with time to progression (TTP) of GC patients treated with CF regimen. These data suggest the potential usefulness of HNRNPC as a prognostic and therapeutic marker of GC.

Gastric cancer is one of the most common human cancers and ranks the second in the global cancer-related mortality. The clinical outcome of patients with advanced gastric cancer (AGC) is markedly dependent on their response to the chemotherapy. Paclitaxel plus capecitabine, as a first-line regimen, is widely administrated in AGC patients, but more than a half of the patients have a poor response, possibly due to their resistance to the treatment. Therefore, it is important to identify potential responders to improve the efficacy of the chemotherapy. In the present study, we used an isobaric tag approach for relative and absolute quantification combined with ESI-QUAD-TOF/MS to identify potential predictive biomarkers for the chemotherapy. We found 211 serum proteins, and confirmed 17 candidates that were differentially present in the progression of disease (PD) group and the partial response (PR) group to the treatment of paclitaxel plus capecitabine. In further validation of the 17 candidates in the set of 12 PD and 12 PR AGC patients, we identified a higher level of AMBP (Alpha-1-Microglobulin/Bikunin Precursor) in the sera of PD patients than of the PR patients assayed by ELISA (9.13 ± 0.45 vs. 8.11 ± 0.26 μg/mL, p = 0.06) and by the Western blotting (relative gray value 396.4 ± 39.1 vs. 275.0 ± 34.76, p = 0.03), respectively. The receiver operating characteristics curve showed 75% sensitivity and 75% specificity of AMBP in AGC patients treated with the chemotherapy. Our data indicated that the high level of serum AMBP could predict the poor response of the AGC patients treated with the paclitaxel-capecitabine chemotherapy, which could be used as a potential biomarker to identify patients who would benefit from this chemotherapeutic regimen.

Background: Rearranged during transfection (RET) rearrangement has been identified as one of the crucial oncogenic drivers in non-small cell lung cancer (NSCLC). Recently, two highly selective RET inhibitors have been approved by the US Food and Drug Administration and demonstrated remarkable responses.However, the clinical characteristics, outcomes and optimal diagnostic method of RET-rearrangements are not well understood. This study sought to evaluate the prevalence and characteristics of RET rearrangement, identify an effective diagnostic method for it, and correlate its presence with outcomes.Methods: A total of 9,431 Chinese NSCLCs from two cancer centers who have undertaken targeted DNA-NGS were enrolled and 167 RET-positive cases were screened. Non-canonical RET rearrangements were confirmed by targeted RNA-NGS. If material was sufficient, positive cases were analyzed by fluorescence in situ hybridization (FISH) (n=30) and immunohistochemistry (IHC) (n=57). Clinicopathologic characteristics, molecular profiling and treatment outcomes of RET rearrangement were evaluated.Results: The prevalence of RET rearrangement was 1.52% (138/9,101) in unfiltered cases and 8.79%(29/330) in EGFR/KRAS/BRAF/ALK-negative cases. RET rearrangement was common in females, never smokers, and lung adenocarcinoma patients. Additionally, 40.3% of stage IV RET-rearranged NSCLC patients developed brain metastases. TP53 was the most common concurrent mutation, and 8 patients harbored concurrent driver oncogenic alterations, including EGFR (N=5), KRAS (N=2), and ALK (N=1).Non-canonical fusion partners were identified in 13.8% (23/167) of cases by DNA-based NGS, and RNAbased NGS identified 3 new partners (EPS8, GOLGA5, and TNIP1). The concordance of FISH and NGS was 83.3% (25/30), while the concordance of IHC and NGS was only 28.1% (16/57). Both IHC and FISH demonstrated lower sensitivity for NCOA4-/other-RET fusions. The CCDC6-RET subgroup had significantly ^ ORCID: 0000-0001-9588-4096. longer progression-free survival than the KIF5B-RET subgroup, both after chemotherapy (23 vs. 9.7 months; P=0.014).Conclusions: RET rearrangement occurs in 1.52% of Chinese NSCLCs and has identifiable clinicopathologic characteristics. RET IHC has a low sensitivity, disavowing its use in routine practice.While NGS and FISH has good performance in identifying RET rearrangement. Both IHC and FISH demonstrated lower sensitivity for NCOA4-/others-RET fusions. Clinical benefit with chemotherapy is different between CCDC6-RET and KIF5B-RET fusion patients, optimal treatment should be considered when selecting therapies for patients with RET-rearranged lung cancers.

Sarsaparilla, also known as Smilax Glabra Rhizome (SGR), was shown to modulate immunity, protect against liver injury, lower blood glucose and suppress cancer. However, its effects on cancer cell adhesion, migration and invasion were unclear. In the present study, we found that the supernatant of water-soluble extract from SGR (SW) could promote adhesion, inhibit migration and invasion of HepG2, MDA-MB-231 and T24 cells in vitro, as well as suppress metastasis of MDA-MB-231 cells in vivo. Results of F-actin and vinculin dual staining showed the enhanced focal adhesion in SW-treated cells. Microarray analysis indicated a repression of TGF-β1 signaling by SW treatment, which was verified by real-time RT-PCR of TGF-β1-related genes and immunoblotting of TGFBR1 protein. SW was also shown to antagonize TGF-β1-promoted cell migration. Collectively, our study revealed a new antitumor function of Sarsaparilla in counteracting invasiveness of a subset of cancer cells by inhibiting TGF-β1 signaling.

No abstract