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To improve the early detection of gastric cancer (GC), there is a growing need for novel and efficient biomarkers. We aimed to evaluate diagnostic value of thioredoxin reductase 1 (TXNRD1), which was found to be over expressed in various malignancies. We found that TXNRD1 has a higher expression level in GC tissues compared with adjacent normal tissues, and high TXNRD1 expression was significantly associated with poor outcomes of GC patients. Next, a total of 1446 cases were collected, with 896 cases in GC, 322 in benign gastric disease and 228 in healthy controls. We noticed plasma thioredoxin reductase (TrxR) level in GC [8.4 (7.1, 9.7) U/ml] was significantly higher than that in benign disease [6.1 (5.4, 7.2) U/ml] or healthy controls [3.7 (1.7, 5.6) U/ml]. Receiver operating characteristic analysis showed that the optimal cutoff value of TrxR activity for GC diagnosis was set at 5.75 U/ml with an area under the curve of 0.945. Moreover, a combined panel of TrxR and routine tumor markers could further elevate the diagnostic efficacy compared to a single biomarker. Finally, by measuring pre- and post-treatment TrxR activity and routine tumor markers, we found the change trend of them was broadly consistent, and plasma TrxR activity was significantly decreased in patients treated with platinum/fluorouracil-based therapy. Our findings recommend plasma TrxR activity combined with tumor markers as effective diagnostic tools for GC patients. As well, plasma TrxR has the potential to monitor therapeutic efficacy.

The burden of breast cancer (BC) has exacerbated over decades. Paclitaxel resistance is responsible for increasing BC treatment burden. Nuclear receptor binding SET domain-containing protein 1 (NSD1) is positively correlated with a poor prognosis in patients with BC. This study investigates the function of NSD1 in paclitaxel-resistant (PR) BC cells. The high levels of NSD1 and Wnt10b in PR BC cell lines (MCF-7/PR) or MCF-7 parental cells were determined by RT-qPCR. Western blotting was conducted to measure the levels of NSD1 protein, apoptosis-associated proteins, Wnt10b protein, H3K36me2 protein, H3K27me3 protein, and signal pathway-associated proteins in MCF-7/PR cells or MCF-7 cells or

Introduction At present, the prognosis of HER2-positive advanced gastric cancer is extremely poor, and some patients fail to benefit from first-line Herceptin treatment, thus facing difficulties in choosing second-line drugs. Case Report Here, we report a 61-year-old male patient with HER2-positive advanced gastric cancer who is primarily resistant to Herceptin and has poor therapeutic effect. Management & Outcome Afterwards, the OncoVeeTM-MiniPDX-guided anticancer method was used to screen drugs for second-line treatment, which resulted in liquefaction and necrosis of the patient's lesions and improved liver function indicators, as well as rapid relief of the patient's clinical symptoms. Discussion In the treatment of the Herceptin-resistant patient with advanced gastric cancer, OncoVeeTM-MiniPDX method screened drugs and brought clinical benefits.

Breast cancer (BC) is regarded as the major cause of cancer-associated deaths in women. Paclitaxel exerts a critical impact on the chemotherapy of BC, but the resistance to paclitaxel becomes a great obstacle in treating the disease. It is reported that noncoding RNA nuclear receptor binding SET domain protein 1 (NSD1) plays a significant role in drug resistance; however, the special role of NSD1 in paclitaxel-resistant BC is unclear. Human BC cell line MCF-7 was used to establish paclitaxel-resistant BC cells (MCF-7/PR). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) displayed that NSD1 and F-box and leucine-rich repeat protein 11 (FBXL11) were highly expressed in BC tissues. Western blotting was utilized for protein level assessment. Cell counting kit-8 (CCK-8), Transwell, wound healing assays, and animal experiments were conducted to examine the influence of NSD1 or FBXL11 on the malignant behaviors of BC in vitro and in vivo, respectively. Transfected MCF-7/PR cells were injected subcutaneously into BALB/c nude mice with or without treatment of paclitaxel. The nuclear factor kappa B (NF-kB) activity was evaluated by the luciferase reporter assay. Results showed that NSD1 knockdown inhibited the epithelial-mesenchymal transition (EMT), migration and invasiveness of BC in vitro, which was rescued by FBXL11 overexpression. Furthermore, NSD1 silencing promoted paclitaxel sensitivity of paclitaxel-resistant BC cells and suppressed tumor growth and paclitaxel resistance in vivo. NSD1 knockdown reduced NF-kB activity, while FBXL11 inhibition markedly increased NF-kB activity. Collectively, NSD1 facilitates the EMT, migration and invasion in paclitaxel-resistant BC cells via regulating NF-kB and FBXL11.

Gastric cancer (GC) is the third leading cause of cancer-associated mortality globally. Although the diagnosis and therapeutic strategies for GC have improved, the prognosis for advanced gastric cancer (AGC) remains poor. Hence, the present study sought to design a zebrafish model established by microinjecting human MGC-803 GC cell line for studying personalized molecular-targeted cancer therapy. Apatinib, a novel molecular-targeted agent, was evaluated for its in vivo efficacy through a comparison among the control groups (no treatment) and subject groups (treatment). Newly formed vessel length and tumor volume were measured in all of the groups for further study. The length of newly formed vessels was obviously shortened after apatinib treatment in the zebrafish model established in this study. Meanwhile, apatinib exhibited the best antitumor growth effect with dose and time dependence by suppressing AKT/GSK3α/β signaling, which may be the mechanism underlying the profound antitumor clinical effect of apatinib. The data indicated that apatinib therapy exerts an anti-angiogenesis effect and it can be recommended as a proper antitumor growth therapy for GC patients. Additionally, zebrafish models could be designed as a potential practical tool to explore new anti-GC cancer drugs.

Background: Circulating tumor cells and serum tumor markers have been found significant in predicting outcome for several malignancies. However, their role in gastric cancer is not fully clarified. We conducted a retrospective study to explore the prognostic value of circulating tumor cells and their applicability in assessing the treatment efficacy in gastric cancers. Methods: From September 2015 to December 2018, 116 patients with newly pathologically diagnosed gastric adenocarcinoma were enrolled. At both baseline and two courses after chemotherapy, the data of circulating tumor cells and serum tumor markers, such as CEA, CA72-4, CA19-9, CA50, and CA242, were collected. The relationships between the change trend of circulating tumor cells and the treatment efficacy were analyzed after chemotherapy, with a paired t-test. Univariate and multivariable analysis were used to find prognostic factors for overall survival (OS). Results: We found there is a significant difference between the circulating tumor cells-positive and circulating tumor cells-negative before and after therapy (mOS 12.6 vs. 31.6 months, PConclusion: Generally, circulating tumor cells provide a novel tool to evaluate the outcomes of gastric cancer patients. Since the change of circulating tumor cells was highly related to treatment response, it may be an auxiliary to assess the effect of chemotherapy, leading an earlier adjustment of following regimens.

Due to the lack of definitive hormone receptors, triple negative breast cancer (TNBC) patients receive little clinical benefit from endocrine or molecular targeted therapies, leading to a highly aggressive disease with a high recurrence rate and poor prognosis. In the past decades, chemotherapy has been the mainstay of treatment for TNBC, with taxane/anthracyclines as the representative regimen. However, increasing irreversible cardiotoxicity of anthracyclines and drug-resistance had to be noticed. Gradually, platinum-based chemotherapy has become a topic of interest for researchers. Based on the accumulating studies on platinum-containing regimens for TNBC patients, we will summarize the progress of relevant clinical trials focusing on platinum monotherapy (e.g., cisplatin, carboplatin and oxaliplatin) or in combination with other therapeutic modalities (e.g., other chemotherapeutic agents, molecular targeted therapies and immunotherapy). To further evaluate patient response to platinum and screen for the optimal population to benefit from platinum, we will also analyze current potential biomarkers, such as breast cancer susceptibility genes (BRCA1/2), homologous recombination repair deficiency (HRD), tumor infiltrating lymphocytes (TILs), TP53 family and other emerging indicators (e.g., intrinsic subtype, cyclin-dependent kinase 2 (CDK2) expression, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9)).

Triple-negative breast cancer (TNBC), a subtype of breast cancer, is defined as lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression. Compared with other subtypes in breast cancer, TNBC is more likely to recur and metastasize, with a lower survival rate. Due to the absence of definitive targets, there was limited novel therapeutic interventions and chemotherapy remained the primary treatment in the past decades. Following the development of immune checkpoint inhibition (ICI) in solid tumors and validation of the immunogenicity in TNBC, immunotherapy has attracted more and more attentions. On basis of accumulating clinical studies, we reviewed the current progress targeting different immune checkpoints in several-lines treatment for TNBC, including programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) inhibitor, and other novel immunotherapeutic approaches (e.g., individualized peptide vaccine, cancer-testis antigen (CTA), new antigen vaccine, RNA vaccine and chimeric antigen receptor modified T cells (CAR-T)). In order to improve the survival outcome of TNBC populations, we further discussed potential predictive biomarkers for immunotherapy (e.g., PD-L1 expression, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), microsatellite instability (MSI)/mismatch repair (MMR) deficiency) and challenges in the future treatment of TNBC.

Supplemental material, sj-pdf-1-jbm-10.1177_1724600820981972 for Circulating tumor cells: A surrogate to predict the effect of treatment and overall survival in gastric adenocarcinoma by Yinxing Zhu, Nan Chen, Manman Chen, Xiaowen Cui, Han Yang, Xuedan Zhu, Jiali Dai, Yang Gong, Dongying Gu, Xinying Huo, Huanhuan Huang and Cuiju Tang in The International Journal of Biological Markers

Objective: To investigate the role and functions of FAM225A in gastric cancer. Methods: The expressions of FAM225A, miR-206, ADAM12 and epithelial-mesenchymal transition (EMT)-related genes were detected by quantitative real-time PCR and Western blot. Functional experiments including cell counting kit-8, colony formation, wound-healing, and Transwell assays were conducted to analyze the biological characteristics of gastric cancer cells in different groups. Bioinformatics, dual-luciferase reporter assay and Pearson correlation coefficients were performed for determining the regulatory relationship of lncRNA-miRNA-mRNA. In vivo nude mouse xenografts and immunohistochemistry were used to verify the results in vitro. Results: In gastric cancer, FAM225A and ADAM12 expressions were up-regulated, while miR-206 expression was down-regulated. Opposite to the regulatory effects of overexpressed FAM225A, blocking FAM225A expression reduced cell viability, migration, invasion and number of cell clones, increased E-Cadherin expression, inhibited N-Cadherin and Vimentin expressions, and ultimately promoted tumor growth. MiR-206 inhibitor partially offset the effects of siFAM225A. Moreover, FAM225A competitively bound to miR-206 to up-regulate ADAM12 expression. Overexpressed ADAM12 partially reversed the effect of miR-206 mimic on the biological characteristics of gastric cancer cells and EMT-related proteins. Conclusion: Our research revealed that FAM225A-miR-206-ADAM12 axis may be a potential pathway for regulating gastric cancer.

Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E2)‐induced paclitaxel resistance and that E2 could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E2 could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel‐resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down‐regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel‐resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.

Antibody-drug conjugates (ADC), a combination of cytotoxic drugs and antibodies, have emerged as a rising star in cancer therapy. Disitamab vedotin (RC48), a novel ADC targeting human epidermal growth factor receptor 2 (HER2), is currently being explored in a variety of malignancies. Compared with conventional HER2-targeting agents, RC48 is characterized by a wider therapeutic window and less toxicity to normal tissues. In this review, we will analyze the structural elements and mechanisms of RC48. Besides, we provide a landscape on the progression of RC48 in common malignancies, focusing on RC48 in gastric or gastroesophageal junction cancer, and a brief overview of urothelial, breast and other cancers (e.g., gynecological cancer, biliary tract cancer, non-small cell lung cancer and myometrial invasive bladder cancer). Finally, we will also discuss future challenges in the development of RC48 and future directions to improve efficacy.

Background Long noncoding RNAs (lncRNAs) are an important class of functional regulators involved in human cancers development, including gastric cancer (GC). Studying aberrantly expressed lncRNAs may provide us with new insights into the occurrence and development of gastric cancer by acting as oncogenes or tumor suppressors. In this study, we aim to examine the expression pattern of lncRNA HAGLROS in GC and its clinical significance as well as its biological role in tumor progression. Methods Bioinformatics analysis and qRT-PCR were performed to detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or loss of function approaches were used to investigate the biological functions of HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony formation assay and nude mouse xenograft model. Wound healing and Transwell assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA-seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to measure molecular mechanisms. Results are shown as means ± S.D. and differences were tested for significance using Student’s t-test (two-tailed). Results We screened out HAGLROS, whose expression was significantly increased and correlated with outcomes of GC patients by publicly available lncRNAs expression profiling and integrating analyses. Exogenous down-regulation of HAGLROS expression significantly suppressed the cell proliferation, invasion and migration. Mechanistic investigations showed that HAGLROS was a direct target of transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR expression and increased autophagy-related genes ATG9A and ATG9B expression. Further investigation showed that HAGLROS regulated mTOR signals in two manners. In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling pathway which was known to be an important negative signal of autophagy. Here activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. Conclusion The present study demonstrates that HAGLROS overexpression contributes to GC development and poor prognosis and will be a target for GC therapy and further develop as a potential prognostic biomarker. Electronic supplementary material The online version of this article (10.1186/s12943-017-0756-y) contains supplementary material, which is available to authorized users.

Molecular targeted therapy of cancer has always been the focus of clinicians. Among those therapeutic targets, the human epidermal growth factor receptor-2 (HER-2) signaling pathway is one of the most popular targets for translational research in cancer. However, unlike prospect in breast cancer, HER-2 inhibitor trastuzumab is the only molecular targeted drug approved by US Food and Drug Administration (FDA) for the first-line treatment of HER-2 positive advanced gastric cancer. On this basis, a variety of novel HER2- targeted drugs for gastric cancer are under development, and related clinical researches are in full swing, including small molecular kinase inhibitors (e.g., afatinib, neratinib, pyrotinib), antibody-drug conjugates (e.g., DS-8201a, RC48-ADC) and other novel therapies (e.g., ZW25, CAR-T, BVAC-B). In this study, we will summarize the recent advances in anti-HER-2 agents, potential mechanisms of resistance to HER2-targeted therapy in HER2-positive gastric cancer. We will also discuss the future prospects of potential strategies to overcome anti-HER-2 resistance and development of novel anti-HER-2 approaches for the treatment of HER2-positive gastric cancer patients.

Wei Xu,1,* Meng Kuang,1,2,* Yang Gong,1 Chunxiang Cao,3 Jinfei Chen,1 Cuiju Tang1 1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, Liyang People’s Hospital, Liyang, Jiangsu, 3Nanjing Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, People’s Republic ofChina *These authors contributed equally to this work and share first authorship Background: The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%–80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC. Methods: PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included. Results: Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73–0.97), progression-free survival (HR, 0.69; 95% CI, 0.59–0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28–2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm. Conclusion: Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population. Keywords: meta-analysis, FOLFOXIRI, FOLFIRI, colorectal cancer, chemotherapy

Rationale: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. Patient concerns: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. Diagnoses: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. Interventions: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. Outcomes: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. Lessons: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.

Genome-wide association studies have identified genes in the transforming growth factor-β (TGFβ) signaling pathway that are responsible for regulating carcinogenesis. We searched for single-nucleotide polymorphisms (SNPs) located within 3′-untranslated regions (3′-UTRs) that might affect the ability of miRNAs to bind genes in the TGFβ pathway for further analysis. We used TaqMan technology to genotype these SNPs in a population-based case–control study of 1147 colorectal cancer patients and 1203 matched controls in a Chinese population. The rs1590 variant of TGFBR1 exhibited a significant association with colorectal cancer risk. Compared with individuals carrying the rs1590 TT genotype, individuals carrying the GT/GG genotypes had a decreased risk of colorectal cancer [odd ratio (OR) = 0.82, 95% confidence interval (CI) = 0.68–0.97], which was more evident among older individuals with a family history of cancer. Luciferase assays confirmed that the rs1590 T allele altered the capacity of miR-532-5p to bind TGFBR1. Based on these findings, the rs1590 variant in the 3′-UTR of TGFBR1 may contribute to the susceptibility to colorectal cancer, predominantly by altering miR-532-5p binding.

Background and Aim Single nucleotide polymorphisms (SNPs) located in long noncoding RNA CASC8 gene may influence the process of splicing and stability of messenger RNA conformation, resulting in the modification of its interacting partners. Genome-wide association studies have identified the SNP rs10505477 and SNP rs1562430 in CASC8 were associated with risk of the colorectal cancer (CRC) and breast cancer, respectively. Methods In the present study, we genotyped the 940 surgically resected gastric cancer patients to explore the association between these two SNPs (e.g. rs10505477 and rs1562430) and survival of gastric cancer in a Chinese population. Results We found that the patients carrying rs10505477 GG genotype survived for a longer time than those with the GA and AA genotypes (log-rank P = 0.030). The similar result was also found in the dominant model (GA/AA vs GG, HR = 1.32, 95% CI = 1.08–1.63, log-rank P = 0.008). This risk effect was more pronounced among patients with tumor size ≤ 5 cm, diffuse-type gastric cancer, lymph node metastasis, no distant metastasis, and TNM stage III and IV. Furthermore, the area under the curve at five years was dramatically increased from 0.619 to 0.624 after adding the rs10505477 risk score to the traditional clinical risk score (TNM stage and lymph node metastasis). However, there was no association be found between the rs1562430 and the survival of gastric cancer. Conclusion These findings suggested the SNP rs10505477 may contribute to the survival of gastric cancer and be a potential prognostic biomarker of gastric cancer.

A number of previous studies have demonstrated that the HFE H63D polymorphism is associated with increased risk of incidence multiple types of cancer, including colorectal cancer, breast cancer, liver cancer, pancreatic cancer, and gynecological malignant tumors. However, the clinical outcomes were inconsistent. Therefore, this meta-analysis was conducted to summarize the effect of the H63D variant on the incidence of solid tumor. PubMed and EMBASE databases were searched for articles associating the HFE H63D polymorphism with cancer risk. The relationships were evaluated by calculating the pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 28 studies, including 7728 cancer cases and 11,895 controls, were identified. Statistically significant associations were identified between the HFE H63D polymorphism and solid cancer risk (CG vs CC, OR = 1.14, 95%CI = 1.07-1.23, P < 0.001; GG vs CC, OR = 1.28, 95%CI = 1.06-1.55, P = 0.010; CG/GG vs CC, OR = 1.16, 95%CI = 1.08-1.24, P < 0.001; GG vs CC/CG, OR = 1.24, 95%CI = 1.02-1.49, P = 0.027). In the subgroup analysis, we illustrated the effect of the H63D polymorphism on hepatocellular carcinoma and pancreatic cancer risk, particularly in the Asian and African subgroups; however, this was not observed in gynecological malignant tumors. In summary, this analysis provided strong evidence that the HFE H63D polymorphism may play a critical role in the increased aggressiveness of hepatocellular carcinoma and pancreatic cancer.

Published data regarding the association between the cytosolic serine hydroxymethyltransferase (SHMT1) C1420T (Leu474Phe) polymorphism and solid tumor risk have shown inconclusive results. To derive a more precise estimation of the relationship, we performed a meta-analysis of 23 published studies that included 14,409 cancer cases and 16,996 controls. A comprehensive search was conducted to identify all eligible studies of the SHMT1 rs1979277 polymorphism and solid tumor risk. The pooled odds ratios (ORs) and the 95% confidence intervals (95%CIs) were calculated using a fixed- or random-effects model. Heterogeneity was represented by PH; publication bias and sensitivity analysis were also explored. Overall, no significant associations were found for any genetic models tested. However, upon stratification by cancer type, a significant decreased risk of breast cancer risk was identified in the homozygote comparison (OR = 0.79, 95%CI = 0.65-0.97 for TT versus CC). An analysis stratified by ethnicity and source of controls revealed an obvious decrease in risk among Asian groups in all genetic models, and among population-based controls only in the homozygote comparison and recessive model. Therefore, our meta-analysis suggested that the SHMT1 C1420T polymorphism was associated with decreased risk of breast cancer. Significant protective effects were found among Asian populations, but not in Caucasian groups. Due to some minor limitations, our findings should be confirmed by further studies.

Whether S-1 could replace 5-Fluorouracil (5-Fu) or not in the treatment of advanced gastrointestinal (GI) cancer (including advanced gastric cancer [AGS] and metastatic colorectal cancer [mCRC]) in Asian patients has been controversial. This meta-analysis was performed to compare the activity, efficacy and toxicity of S-1-based versus 5-Fu-based chemotherapy in those Asian patients. Randomized controlled trials (RCTs) were identified by electronic search of Pubmed. Relevant abstracts were manually searched to identify relevant trials. A total of 2182 patients from eight RCTs were included, and our results demonstrated that S-1-based chemotherapy significantly improved overall survival (OS) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–1.00) and overall response rate (ORR) (odds ratio [OR], 1.72; 95% CI, 1.09–2.70), but no significant progression-free survival (PFS) benefit was found between arms (HR, 0.87; 95% CI, 0.72–1.06). Subgroup analyses revealed that S-1-based chemotherapy significantly improved OS and ORR in subgroups of patients with non-platinum containing regimens (P = 0.041; P = 0.034) and patients with no prior chemotherapy history (P = 0.025; P = 0.016). Statistically significant improvements of PFS and ORR in the S-1-based chemotherapy were observed in the subgroup of patients with AGC (P < 0.001; P = 0.005). S-1-based chemotherapy was characterized by significantly higher incidences of diarrhea, fatigue and thrombocytopenia, and a lower incidence of nausea. This analysis provided strong evidence for survival benefits of S-1, and S-1-based chemotherapy could be considered to replace 5-Fu-based therapy for the treatment of advanced GI cancer in Asian patients.

The FAS, FAS ligand (FASL), and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the survival of gastric cancer are unknown. In this study, we investigated the association of four polymorphisms (FAS −1377G > A, −670A > G, FASL −844C > T, and CASP8 −652 6N ins > del) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan–Meier method, Cox proportional hazards models and the log-rank test. Our results revealed that individuals with CASP8 −652 6N ins/del + del/del genotypes had a decreased risk of death compared with those with ins/ins genotype (log-rank P = 0.005; hazard ratio = 0.75, 95% confidence interval = 0.62–0.92). The protective effect of the del allele was further confirmed in subgroups of patients with tumor size ≤5 cm (0.66, 0.50–0.86) and T2 depth invasion (0.59, 0.37–0.94), but no significant association was observed in the subgroups of lymph node metastasis (0.67, 0.47–0.97), and distance metastasis (0.73, 0.60–0.90). Our findings suggest that, if validated in different independent populations, the CASP8 −652 6N ins > del polymorphism may serve as a promising genetic marker for gastric cancer prognosis. Environ. Mol. Mutagen. 55:421–427, 2014. © 2014 Wiley Periodicals, Inc.

UNLABELLED A genome-wide association study revealed that a single nucleotide polymorphism, CLPTM1L - rs401681 (G>A), located at the 5p15.33 locus was significantly associated with increased risk of various cancers; however, its association with lung cancer is currently inconclusive. In order to explore the relationship between this polymorphism and lung cancer risk more precisely, we performed a meta-analysis of eight eligible studies involving 9935 cases and 11,261 controls. The pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed- or random-effect models. Results indicated that this polymorphism was significantly associated with lung cancer risk in all genetic models (GA vs GG: OR = 0.88, 95%CI = 0.83-0.94; AA vs GG: OR = 0.81, 95%CI = 0.70-0.93; AA/GA vs GG: OR = 0.86, 95%CI = 0.81-0.91; AA vs GA/GG OR = 0.86, 95%CI = 0.76-0.99). An analysis stratified by ethnicity and source of controls revealed a significantly decreased risk among European groups and population-based studies in all genetic models, and among Asian populations only in the dominant model comparison. Additionally, in a subgroup analysis by histology type, the CLPTM1L rs401681 polymorphism was found to significantly decrease the risks of both adenocarcinoma and squamous cell carcinoma of the lung in all genetic models. In conclusion, our study indicated that the CLPTM1L - rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations. Due to some minor limitations, our findings should be confirmed in further studies.

Polymorphisms of the DNA repair gene X-ray repair cross-complementing protein 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln have been shown to alter the DNA repair activity and to be associated with genetic susceptibility to several types of cancer. We indentified genotypes of 944 surgically resected gastric cancer (GC) patients by the SNaPshot method to investigate the association of these polymorphisms with clinical progression and outcomes of GC in a Chinese population. The XRCC1 codon 280 His carriers (Arg/His+His/His) held a significantly lower risk of distant metastasis in the dominant model (Pearson chi-square test P=0.019). A weak association of these cases with reduced risk of lymph node metastasis was also found (Pearson chi-square test P=0.051). Individuals carrying at least one Trp allele of XRCC1 codon 194 had an increased risk of death compared with those with Arg/Arg homozygotes in diffuse-type GC (adjusted hazard ratio=1.34, 95% confidence interval=1.05-1.71). Our findings demonstrated that the genetic variant Arg280His in XRCC1 may contribute to cancer progression and that XRCC1 Arg194Trp variants may act as a favorable prognostic indicator of resected GC, particularly among the diffuse-type GC. Larger studies are needed to verify our results in different populations.

Recently, the need for maintenance chemotherapy arose as a result of the significantly improved survival of patients with metastatic colorectal cancer (mCRC) without increasing adverse events. Currently used maintenance regimens are fluoropyrimidines, bevacizumab, and the combination of fluoropyrimidine with bevacizumab. A new combination with bevacizumab and erlotinib, a tyrosine kinase inhibitor of the epithelial growth factor receptor, has shown synergistic effects in preclinical tests and promising results in some clinical trials. Whether bevacizumab combined with erlotinib vs. bevacizumab alone as maintenance therapy will further improve the clinical outcomes in patients with mCRC is controversial. We conducted this meta-analysis to compare the survival benefit and safety of these two regimens in patients with mCRC. We searched PubMed, EMBASE, and the Central Registry of Controlled Trials of the Cochrane Library up to August 2016. We also searched the Proceedings of the American Society of Clinical Oncology (1986 to August 2016). Abstracts were manually searched to identify relevant trials. A total of three randomized controlled trials with 682 patients met the inclusion criteria. Our results demonstrated that bevacizumab combined with erlotinib significantly improved overall survival (hazard ratio 0.78; 95 % confidence interval 0.66–0.93; p = 0.006) and progression-free survival (hazard ratio 0.79; 95 % confidence interval 0.68–0.92; p = 0.002). Significantly more grade 3 rash, diarrhea, infection total, and fatigue were observed in the bevacizumab combined with erlotinib arm, which were controllable and reversible. Based on current evidence, the addition of erlotinib to bevacizumab as maintenance therapy significantly increases overall survival and progression-free survival with an increased but manageable toxicity in patients with mCRC. It should be considered as a treatment option for these patients under the premise of a reasonable selection of the target population.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide and is highly resistant to chemotherapy. Yes-associated protein (YAP) is the downstream effector of the Hippo signaling pathway, which is frequently overexpressed in many types of cancers. Amplification of the YAP gene and overexpression of YAP in HCC have previously been reported to contribute to hepatocyte malignant transformation and tumor progression. In this study, we aimed to investigate the potential role of YAP in HCC chemoresistance. Overexpression of YAP resulted in resistance against doxorubicin-induced apoptosis in HCC cell lines, whereas suppression of the endogenous YAP expression by RNA interference demonstrated the reverse effect. Western blotting revealed that, following exposure to doxorubicin, YAP-overexpressing cells exhibited decreased cleaved PARP, increased phosphorylation of Akt and ERK1/2, and elevated Bcl-xL expression in comparison to the vector control. Inhibition of YAP expression sensitized HCC cells to doxorubicin, by exhibiting increased cleaved PARP, decreased levels of phosphorylated Akt, phosphorylated ERK1/2 and Bcl-xL expression. In addition, pretreatment with the MEK1/2 inhibitor U0126 but not the PI3-K inhibitor LY294002 significantly enhanced doxorubicin-induced apoptosis and decreased Bcl-xL expression in YAP-overexpressing HCC cells. Our data provide evidence that overexpression of YAP plays an important role in conferring doxorubicin resistance to HCC, which is at least partially mediated by YAP-induced activation of the MAP kinase pathway. Targeting YAP may be a promising adjunct for overcoming doxorubicin resistance in HCC.

In order to make a comprehensive assessment of the potential association between two genetic variants in the IL-10 gene promoter, -1082 A>G (rs1800896) and -592 C>A (rs1800872), and colorectal cancer (CRC) risk, we conduced a meta-analysis of seven epidemiological studies, which included 1469 colorectal cancer cases and 2566 controls. Neither of the two polymorphisms had any association with increased CRC risk in overall population [for rs1800896: odds ratio (OR) = 0.90, 95% confidence interval (95%CI) = 0.76-1.06 in the dominant model and for rs1800872: OR = 1.06, 95%CI = 0.91-1.23 in the dominant model]. In subgroup analysis of the rs1800896 polymorphism, the results did not change when the analyses were restricted to individual studies, or those fulfilling Hardy-Weinberg equilibrium, or according to the source of controls. For rs1800872, however, when stratifying by the source of controls, the A allele had a significant increased risk of CRC among studies with population-based controls in the codominant model (AC vs CC: OR = 1.30, 95%CI = 1.04-1.63) and dominant model (AA/AC vs CC: OR = 1.25, 95% CI = 1.01-1.55). Based on this meta-analysis, we conclude that the IL-10 rs1800872 polymorphism could be a risk factor for CRC development among European populations. However, we found no association between the IL-10 rs1800896 polymorphism and CRC risk. Further studies, either with larger sample size or involving other SNPs and haplotypes of the IL-10 gene, are necessary to clarify the contribution of IL-10 genetic variations in colorectal carcinogenesis.

e18569Background: Gastric cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence clinical...

A large number of randomized controlled trials involving chemotherapy in the management of advanced colorectal cancer were conducted. 5-FU/LV in combination with irinotecan (IRI) or oxaliplatin (OXA) was used. The aim of the meta-analysis was to compare and evaluate the effectiveness and safety of the two therapeutic approaches for patients with advanced colorectal cancer. A literature search, study selection and assessment, data collection, and analysis were undertaken by two reviewers according to the Cochrane Handbook for Systematic Reviews of Interventions. Randomized controlled trials (RCTs) or quasi-RCTs comparing IRI versus OXA, in combination with 5-FU/LV in the treatment of advanced colorectal cancer were performed. Seven studies involving 2,107 patients met the inclusion criteria. The OXA + 5-FU/LV regimen showed a significant increase in survival by lower hazard ratios (HR) [HR 1.28; 95% CI (1.13-1.45)] and was associated with lower toxicities. The OXA + 5-FU/LV regimen was superior or equal to the IRI + 5-FU/LV regimen in prolonging time to progression and median survival. The IRI + 5-FU/LV regimen resulted in higher hazard ratios in nausea vomiting/emesis and diarrhea [HR 1.99, 95% CI (1.19-3.31); HR 1.83, 95% CI (1.38-2.44)] and lower hazard ratios in paresthesia, sensory neuropathy, and thrombocytopenia [HR 0.09, 95% CI (0.03-0.23); HR 0.04 95% CI (0.01-0.13); HR 0.19 95% CI (0.05-0.64)] than the OXA + 5-FU/LV regimen. Compared with IRI, OXA is more appropriate for the treatment of advanced colorectal cancer when combined with 5-FU/LV. OXA + 5-FU/LV should be considered as the first-line standard of care for advanced CRC patients.

To observe the effects of p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency (PWL), histology and the spinal levels of IL-1β and TNF-α were detected. All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs (12.12 ± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days) were significant higher than that of controls (9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days), P < 0.05. Meanwhile, intrathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting intracellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.

UNLABELLED Breast cancer (BC) is the most widespread cause of cancer-related deaths in women. Many published studies have assessed the association between the glutathione S-transferase P1 (GSTP1) rs1695 polymorphism and BC risk. However, the effect of the GSTP1 rs1695 polymorphism on BC risk has remained controversial. Therefore, this meta-analysis was conducted to obtain a comprehensive estimation of this association. A total of 20,615 cases and 20,481 controls from thirty-six case-control trials were extracted from an online literature survey. The meta-analysis indicated that the GSTP1 rs1695 A>G polymorphism did not contribute to the susceptibility of BC when the overall population was considered. However, intriguingly, this polymorphism was significantly associated with increased risk of BC in Asian women [GG vs AA: odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.06-1.88, P = 0.02; AG vs AA: OR = 1.08, 95%CI = 1.00-1.16, P = 0.05; GG/AG vs AA: OR = 1.11, 95%CI = 1.04-1.19, P = 0.00]. Moreover, a subgroup analysis based on the source of control groups showed a marked increase in BC susceptibility in hospital-based control subjects (GG vs AA: OR = 1.28, 95%CI = 1.10-1.48, P= 0.00; GG vs AG/AA OR = 1.22, 95%CI = 1.06-1.41, P = 0.00; GG/AG vs AA: OR = 1.10, 95%CI = 1.02-1.18, P = 0.00). In conclusion, our study indicated that the GSTP1 rs1695 A>G polymorphism was correlated with elevated BC risk in Asian women. Our results must be validated with further research.

OBJECTIVE Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed meta-analysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone. METHODS STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ(2) test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed. RESULTS Four randomized controlled trials including 878 Asian patients were analyzed. In total meta-analysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256). CONCLUSION This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.

The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679–0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size &gt, 5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size &gt, 5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.

Recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese population has identified two novel single nucleotide polymorphisms (SNPs) rs11066280 and rs2074356 on C12orf51 gene. We hypothesized that SNPs rs11066280 and rs2074356 could influence gastric cancer survival outcomes. We genotyped the SNPs rs11066280 and rs2074356 in 940 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs11066280 and survival of gastric cancer. However, in the stratification analysis of histology, we found that the rs11066280 TA/AA genotypes were associated with a poor survival of intestinal-type gastric cancer (log-rank P = 0.041, hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.02–1.93), Moreover, this hazardous effect was more prominent among patients with tumor size > 5 cm, no distant metastasis, chemotherapy and drinking. No significant association was observed between rs2074356 and the survival of gastric cancer. C12orf5 rs11066280 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the intestinal-type gastric cancer.

Single nucleotide polymorphisms (SNPs) located in long noncoding RNA CASC8 gene may influence the process of splicing and stability of messenger RNA conformation, resulting in the modification of its interacting partners. Genome-wide association studies have identified the SNP rs10505477 and SNP rs1562430 in CASC8 were associated with risk of the colorectal cancer (CRC) and breast cancer, respectively.In the present study, we genotyped the 940 surgically resected gastric cancer patients to explore the association between these two SNPs (e.g., rs10505477 and rs1562430) and survival of gastric cancer in a Chinese population.We found that the patients carrying rs10505477 GG genotype survived for a longer time than those with the GA and AA genotypes (log-rank P = 0.030). The similar result was also found in the dominant model (GA/AA vs GG, HR = 1.32, 95% CI = 1.08-1.63, log-rank P = 0.008). This risk effect was more pronounced among patients with tumor size ≤ 5 cm, diffuse-type gastric cancer, lymph node metastasis, no distant metastasis, and TNM stage III and IV. Furthermore, the area under the curve at five years was dramatically increased from 0.619 to 0.624 after adding the rs10505477 risk score to the traditional clinical risk score (TNM stage and lymph node metastasis). However, there was no association be found between the rs1562430 and the survival of gastric cancer.These findings suggested the SNP rs10505477 may contribute to the survival of gastric cancer and be a potential prognostic biomarker of gastric cancer.

Objectives Genome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis. Methods We genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer. Results Our findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P = 0.028 for AC versus AA/CC, hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.03–1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients. Conclusions In conclusion, we demonstrate that MAP3K1 rs889312 is closely correlated with outcome among diffuse-type gastric cancer. This raises the possibility for rs889312 polymorphisms to be used as an independent indicator for predicting the prognosis of diffuse-type gastric cancer within the Chinese population.

The FAS, FAS ligand (FASL), and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the survival of gastric cancer are unknown. In this study, we investigated the association of four polymorphisms (FAS -1377GA, -670AG, FASL -844CT, and CASP8 -652 6N insdel) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. Our results revealed that individuals with CASP8 -652 6N ins/del+del/del genotypes had a decreased risk of death compared with those with ins/ins genotype (log-rank P=0.005; hazard ratio=0.75, 95% confidence interval=0.62-0.92). The protective effect of the del allele was further confirmed in subgroups of patients with tumor size ≤ 5 cm (0.66, 0.50-0.86) and T2 depth invasion (0.59, 0.37-0.94), but no significant association was observed in the subgroups of lymph node metastasis (0.67, 0.47-0.97), and distance metastasis (0.73, 0.60-0.90). Our findings suggest that, if validated in different independent populations, the CASP8 -652 6N insdel polymorphism may serve as a promising genetic marker for gastric cancer prognosis.

Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.