Altered mitochondrial function contributes greatly to pathogenesis and progression of colorectal cancer. In this study, we report a functional pool of Src homology 2 domain-containing F (SHF) in mitochondria controlling the response of colorectal cancer cells to radiation therapy. We found that elevated expression of SHF in cancer cells is essential for promoting mitochondrial function by increasing mitochondrial DNA copy number, thus reducing the sensitivity of colorectal cancer cells to radiation. Mechanistically, SHF binds to mitochondrial DNA and promotes POLG/SSBP1-mediated mitochondrial DNA synthesis. Importantly, SHF loss-mediated radiosensitization was phenocopied by depletion of mitochondrial DNA. Thus, our data demonstrate that mitochondrial SHF is an important regulator of radioresistance in colorectal cancer cells, identifying SHF as a promising therapeutic target to enhance radiotherapy efficacy in colorectal cancer.

Mitochondrial respiration and metabolism play a key role in the pathogenesis and progression of colon adenocarcinoma (COAD). Here, we report a functional pool of FKBP4, a co-chaperone protein, in the mitochondrial intermembrane space (IMS) of colon cancer cells. We found that IMS-localized FKBP4 is essential for the maintenance of mitochondrial respiration, thus contributing to the sensitivity of COAD cells to 5-fluorouracil (5-FU). Mechanistically, FKBP4 interacts with COA6 and controls the assembly of the mitochondrial COA6/SCO1/SCO2 complex, thereby governing COA6-regulated biogenesis and activity of mitochondrial cytochrome c oxidase (complex IV). Thus, our data reveal IMS-localized FKBP4 as a novel regulator of 5-FU sensitivity in COAD, linking mitochondrial respiration to 5-FU sensitivity in COAD.

Colon cancer cells rely on mitochondrial respiration as major source of energy for supporting their proliferation and invasion, thus promoting colon cancer malignancy and progression. In this study, we comprehensively investigated the prognostic significance of mitochondria-related genes in colon cancer and identified the hub genes that control colon cancer cell mitochondrial respiration and proliferation. We first systematically evaluated the prognostic significance of differentially expressed mitochondria-related genes in colon cancer specimens. Furthermore, a protein–protein interaction network was constructed to explore the hub genes. Eventually, five hub genes were identified, namely, POLG, FASTK, MRPS5, AARS2, and VARS2. Functional analyses showed that all these five hub genes are essential for maintaining mitochondrial respiration and proliferation of colon cancer cells. Mechanistic studies revealed the roles of these five hub genes in modulating mitochondrial DNA expression, that in turn influence mitochondrial respiration. In summary, our study demonstrated that POLG, FASTK, MRPS5, AARS2, and VARS2 may potentially serve as prognostic biomarkers and therapeutic targets for colon cancer.

Background: Microsatellite instability-high (MSI-H) is a special type of human colon adenocarcinoma (COAD) that responds well to immunotherapy.MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are important members of competing endogenous RNAs (ceRNAs) networks, are involved in the tumorigenesis and development of MSI-H COAD.This study aimed to establish a ceRNA network for MSI in COAD to identify targets and prognostic markers that may explain the effects of immunotherapy.Methods: COAD sequencing data were extracted from The Cancer Genome Atlas (TCGA), after which differentially expressed miRNAs, lncRNAs, and mRNAs were determined according to microsatellite status.After building a network based on the ceRNA hypothesis, the relationships between microsatellite status and clinical features were explored.Biological processes in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were analyzed for specific miRNAs, lncRNAs, and mRNAs.Survival analysis was used to identify potential biomarkers.Results: Based on the inclusion criteria, a total of 363 COAD samples were obtained from TCGA.Strict screening criteria were used to identify differentially expressed RNAs in the MSI-H and microsatellite-stable groups, with 82 miRNAs, 1,280 lncRNAs, and 2121 mRNAs obtained (fold change >2, false discovery rate <0.01).Based on the RNA interaction mechanism, a miRNA-lncRNA-mRNA network was constructed, through which a subnetwork composed of 5 miRNAs was discovered.hsa-miR-31-5p, hsa-miR-302a-3p, hsa-miR-302b-3p, hsa-miR-302d-3p, hsa-miR-3619-5p and the RNAs interaction with them have the potential to become novel targets to change the effect of existing immunotherapy.GO and KEGG analyses showed that these differentially expressed miRNAs, lncRNAs, and mRNAs may play key roles in tumorigenesis, tumor development, and drug efficacy, with natural killer cells potentially becoming the next emerging targets for immunotherapy enhancement.Moreover, survival analysis identified 10 lncRNAs as potential survival markers.Conclusions: This study identified novel immunotherapy targets and revealed potential biomarkers for COAD according to microsatellite status.

Mitochondria, as the only metabolic organelles which exist independently of the cell nucleus with DNA, play an important role in the development and progression of colorectal cancer. There are many researches about the relationship between colorectal cancer and mitochondrial DNA (mtDNA) emerge in endlessly. As the starting site of transcription and replication, displacement loop region (D-loop) region becomes one of the hot spots among these researches. In this paper, we reviewed the progress research about the correlation between mutations, polymorphisms, methylation, microsatellite instability and copy number changes of D-loop region and colorectal cancer. Some studies have shown that the presence of tumor D-loop mutations are associated with poor prognosis and can be used as a predictor of postoperative adjuvant chemotherapy in patients with stage Ⅲ colorectal cancer. The frequent haplotypes of secondary haplotypes of nucleotide 16290T and the frequent haplotypes of nucleotide 16298T in hypervariable region 1 (HV1) are associated with the high survival rates of colorectal cancer, and the polymorphism at position 16 290 is identified as independent predictors of colorectal cancer prognosis. The demethylation of the D-loop region may be involved in the regulation of mtDNA copy number and nicotinamide adenine dinucleotide dehydrogenase subunit 2 (ND-2) expression, and its microsatellite instability is associated with drug resistance and poor prognosis of the fluorouracil-based adjuvant chemotherapy. Due to D-loop region as an important transcriptional initiation region of mtDNA, the in-depth and comprehensive study will help us understand its role in the pathogenesis and progression of colorectal cancer, and further provide guidance for clinical diagnosis and treatment.

In the era of precision medicine, establishing a patient-derived cell model is crucial, whether in vitro or in vivo. Compared to the traditional cell lines, patient-derived primary cells represent precise genetic features from specific patients, but poor proliferative activity of human primary cells restricts their popular application. Conditional reprogramming (CR) is a new cell culture technique to achieve rapid growth of patient-derived cells in vitro, making it possible to identify the individual difference and screen drugs sensitivity. In this review, we will summarize the application and limitation of CR in tumor and inflammatory-related diseases, indicating the prospect of this technique for preclinical research.

Colorectal cancer (CRC) is one of the most commonly diagnosed tumors among human worldwide. Angiogenesis and tumor-associated macrophage (TAM) recruitment are closely associated with CRC development. Nevertheless, the mechanisms revealing CRC progression are still not fully understood. 5′-Nucleotidase domain containing 2 (NT5DC2), a member of the NT5DC family, modulates various cellular events to mediate tumor growth, and thus serves as a disgnostic biomarker. Here, we explored the potential of NT5DC2 on tumor progression in CRC. We first found that NT5DC2 expression was significantly up-regulated in CRC tissues and cell lines. CRC patients with higher NT5DC2 expression showed poor overall survival. Furthermore, CRC cell lines stably transfected with shNT5DC2 lentivirus plasmids exhibited markedly reduced cell proliferation, migration and invasion compared with the negative control group. Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) expression levels were remarkably reduced in CRC cells with NT5DC2 deletion, along with evidently reduced tube formation in the HUVECs cultured in the collected conditional medium. The expression levels of CC chemokine ligand 2 (CCL2) and its receptor CCR2 were found to be greatly down-regulated in CRC cells transfected with shNT5DC2. Moreover, NT5DC2 knockdown markedly suppressed the activation of protein kinase-B/nuclear transcription factor κB (AKT/NF-κB) signaling in CRC cells. Furthermore, we found that NT5DC2 deletion obviously reduced the TAM recruitments through suppressing CCL2/CCR2 and AKT/NF-κB signaling pathways. Intriguingly, our in vitro experiments demonstrated that VEGF reduction was necessary for shNT5DC2-inhibited cell proliferation, migration, invasion, angiogenesis and TAM recruitment. In vivo studies also confirmed that NT5DC2 knockdown effectively reduced the tumor growth and VEGF expression in a xonegraft mouse model with CRC. Lung metastasis of CRC cells was also hindered by NT5DC2 deletion in vivo. Collectively, our results indicated a previously unrecognized NT5DC2/VEGF/CCL2 axis involved in CRC development and metastasis.

Study purpose: Previously, we had a pilot study to evaluate the feasibility of a stool DNA test of methylated Syndycan-2 (SDC2) for colorectal cancer (CRC) detection. The purpose of this continuing investigation was to assess the performance of this test in a multicenter hospital-based setting. Methods: Each participant was required to undergo both a stool DNA test and a reference colonoscopy. The stool DNA test assesses the methylation status of a single target of SDC2 gene. Results of real-time methylation-specific PCR were dichotomized as positive and negative by a prespecified cut-off value. The main evaluation indexes were sensitivity, specificity, and kappa value, which was used to assess the diagnostic consistency between stool DNA test and colonoscopy. Tests were performed in blinded fashion and processed independently of the colonoscopic results. Results: Among the 1110 participants from three hospitals included for analysis, 359 and 38 had CRC and advanced adenomas, respectively, according to colonoscopy findings. The sensitivity of the stool DNA test was 83.8% for CRC and 42.1% for advanced adenomas. For CRC at early stage confined to bowel wall (I to II), the sensitivity was 87.0%. Detection rate for CRC did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender (P=0.041). The specificity of the stool DNA test was 98.0% among participants with nonadvanced colorectal neoplasia, non-neoplastic disorders, or negative results on colonoscopy. Diagnostic consistency for CRC assessed by kappa value was 0.84, indicating that the agreement in outcome between the stool DNA test and colonoscopy was excellent. Conclusion: Noninvasive stool DNA test using methylated SDC2 as a molecular marker was a sensitive and accurate method for CRC detection. Citation Format: Jianping Wang, Side Liu, Hui Wang, Lei Zheng, Changchun Zhou, Guoxin Li, Rongkang Huang, Huaiming Wang, Chujun Li, Xinjuan Fan, Xinhui Fu, Xinying Wang, Hongliang Guo, Jie Guan, Yanlai Sun, Xilin Song, Zengjun Li, Dianbin Mu, Jujie Sun, Xianglin Liu, Yan Qi, Feng Niu, Chunhua Chen, Xiaolin Wu, Xianshu Wang, Xianrang Song, Hongzhi Zou. A multicenter clinical study of stool DNA test of methylated syndecan-2 for colorectal cancer detection [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4611.

Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8–95.4), 85.9% (95% CI 84.7–87.1), and 78.8% (95% CI 77.0–80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count < 6 per 50 high-power fields [HPFs]) + 1.442 (tumor mitotic count between 6 and 10 per 50 HPFs) + 2.026 (tumor mitotic count > 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

Background and Aims Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. Methods Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. Results Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I–II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. Conclusion Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. Chinese Clinical Trial Registry Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

e15515 Background: Apatinib, a small molecule tyrosine kinase inhibitor, has been approved to use in patients with advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after at least two systemic chemotherapy regimens in China. This study aims to observe the efficacy and safety of apatinib in real word clinical practice and preliminarily explore the characteristics of population with more clinical benefit. Methods: This study included patients with non-operative or advanced gastric cancer confirmed by histopathology or cytology, and did not intervene the regimen which was entirely determined by the clinicians and patients. Results: From April 16, 2018 to January 12, 2019, 732 patients enrolled, and all patients had been followed up at least once. Total 342 patients were eligible for efficacy evaluation. Among them, 43 patients achieved partial response (PR), 209 patients achieved stable disease (SD) and 90 patients experienced progression disease (PD). The overall response rate (ORR) was 12.55%, and the disease control rate was 73.6%. The mPFS have not yet reached. For patients ≥65 years, the ORR was 26.32%, and for patients < 65 years, ORR was 8.33%. For patients with non-signet ring cell carcinoma and signet ring cell carcinoma, the ORRs were 15.22% and 6.0%. For patients with and without organ metastasis, the ORRs were 15.25% and 3.75% respectively. The PFS analysis showed that, Combined chemotherapy and age > 65 may predict longer PFS. The OS analysis showed that, ECOG 0-1, combined chemotherapy, AFP positive and male predict longer OS. The overall incidence of adverse events was 84%. The most common adverse events were hypertension (28.8%), fatigue (22.4%), hand-foot syndrome (17.3%), anorexia (12.8%) and nausea (10.5%). Conclusions: Apatinib showed promising antitumor activity in patients with non- operable or advanced Gastric Cancer in this real word study. The prolonging survival benefits maybe could be attenuated by age <65, without organ metastasis, ECOG score >1, treatment regimen, normal AFP, and pathological diagnosis of non-signet ring cell carcinoma. Clinical trial information: ChiCTR1800015701.

Long non-coding RNAs (lncRNAs) have been shown to participate in cancer progression. In the present study, we explored the potential roles of lncRNA-PVT1 in the development process of colorectal cancer (CRC) via miR-455. We found that PVT1 is up-regulated in human CRC tissues compared to adjacent normal tissues. A functional study showed that the silencing of PVT1 expression by siRNAs inhibited cell proliferation, migration and invasion, whereas the overexpression of PVT1 accelerated cell proliferation, migration and invasion in vitro. A mechanistic study indicated PVT1 regulated the growth of CRC tumors by acting as a competing endogenous RNAs (ceRNA) and negatively regulated miR-455. Furthermore, we discovered that RUNX2, a functional transcription factor in CRC, up-regulated PVT1 expression. Therefore, our study suggested that the RUNX2/PVT1/miR-455 regulatory axis plays an important role in CRC tumorigenesis and may be a therapeutic target for the treatment of CRC.

Gastrointestinal cancer (GIC) is a worldwide public health problem with a high mortality rate. Mitochondrial DNA (mtDNA) mutations in the displacement loop (D‑loop) region are quite common in various types of primary human cancers; however, their role in the pathogenesis of GIC is controversial. In the present study, tumor and para‑tumor tissues were selected from 18 patients with gastric cancer (GC), 21 patients with colon cancer (CC) and 30 patients with rectal cancer (RC). The mtDNA D‑loop was analyzed by sequencing and reverse transcription‑quantitative polymerase chain reaction. Furthermore, DNA oxidative damage and DNA repair functioning were detected by immunohistochemistry. The results demonstrated that increased mtDNA deletion was not evident in GIC; however, significant DNA oxidative damage was significant in RC by detecting 8‑hydroxyguanine expression. In addition, over‑activated DNA repair was identified in CC and RC through the detection of 8‑oxo‑20‑deoxyguanosine glycosylase 1 expression. The mtDNA D‑loop had a specific mutation hotspot region, and the level of mtDNA D‑loop mutations was correlated with the progression of the GIC. The mutations of the mtDNA D‑loop were primarily homoplasmic in GIC and often transitioned at pyrimidine sites. Mitochondrial microsatellite instability, including the formation of poly‑cytidine stretches, was common in GIC. These results demonstrate the occurrence of mtDNA D‑loop mutations in GIC in Chinese patients and support the correlation of these mutations with carcinoma progression. Over‑activated DNA repair function possibly repairs the GIC mtDNA lesions.

Background: The role of radiaotion therapy in resectable gastric cancer patients without distant metastases remains controversial.This retrospective analysis was performed to identify whether resectable gastric cancer patients without distant metastases might benefit from radiation.Results: The results of the Kaplan-Meier analysis and log-rank test showed that a total of 3309 patients had a MST of 29.0 months, a 1-year survival rate of 74.7%, and a 3-year survival rate of 45.5%.Among them, the MST of the "RPS" group and the "RAS" group were significantly longer compared with that of the "No Radiation" group (32.7vs 32.9 vs 25.3 months, P < 0.05).The 1-year survival rates were 83.7%, 83.5% and 65.6% for the "RPS", "RAS" and "No radiation" groups, respectively (P < 0.05) and the 3-year survival rates were 52.6%, 63.6% and 44.9%, respectively (P < 0.05).The multivariate Cox proportional hazard regression analysis showed that radiation was an independent prognostic factor.Materials and Methods: A total of 5744 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer without distant metastases from 2010 to 2013 were included.Patients were divided into three groups as follows: patients who underwent radiation after surgery ("RAS" group), patients who underwent radiation prior to surgery ("RPS" group) and patients who did not undergo radiation ,only surgery performed ("No radiation'"group).Conclusions: This retrospective analysis demonstrated that "RPS" or "RAS"alone were independent prognostic factors for survival improvement in selected gastric cancer patients without distant metastases.

Objective: To investigate the effect of Δ40p53, an alternative spliced isoform of p53 lacking the N-ter minus, on the pro-apoptotic function of p53. Methods: The wild-type p53 was ectopically expressed in HCT116-p53(-/-) (endogenous Δ40p53 expression), HCT116-p53(+ /+) (wild-type p53) and H1299 (p53-null) cells by adenoviral delivery, while Δ40p53 plasmid were transfected into these cells to overexpress Δ40p53. The levels of Δ40p53 and p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR. The expression of related proteins was deter mined by Western blotting. The interaction of p53 and Δ40p53 was observed by co-immunoprecipitation assay. Calcein-AM/propidium iodide (PI) staining and flow cytometry were used to detect the apoptotic rate of tested cells in each group. Results: HCT116-p53(-/-) cells expressed endogenous Δ40p53 isoform. Neither transcription nor protein expression of wild-type p53 was interfered by the increased expression of Δ40p53. Full length p53 and Δ40p53 could bind to each other. Calcein-AM/PI staining showed that the apoptotic rates of H1299-Control, HCT116-p53(-/-) -Control, H1299+ p53, HCT116-p53(-/-)+ p53, H1299+ oxaliplatin (Oxa), HCT116-p53(-/-)+ Oxa, H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups were (2.50±0.47)%, (2.40±0.32)%, (5.20±0.58)%, (4.10±0.18)%, (22.40±1.73)%, (19.30±1.11)%, (29.90±1.15)% and (39.30±2.26)%, respectively. It was statistically significant between H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups (t=3.721, P=0.0205). Moreover, the apoptotic rates of H1299-Control, H1299+ Δ40p53, H1299+ p53, H1299+ p53+ Δ40p53, H1299+ Oxa, H1299+ Δ40p53+ Oxa, H1299+ p53+ Oxa and H1299+ p53+ Δ40p53+ Oxa groups were (2.60±0.35)%, (2.20±0.17)%, (4.80±0.49)%, (4.90±1.10)%, (20.30±1.10)%, (19.60±1.45)%, (27.90±1.39)%, (35.20±1.43)%, respectively. Furthermore, flow cytometry assay showed that the apoptotic rates of above cells were (2.70±0.32)%, (2.20±0.24)%, (4.60±0.48)%, (3.90±0.67)%, (19.30±1.11)%, (17.70±0.66)%, (28.30±2.76)% and (37.50±1.51)%, respectively. H1299+ p53+ Δ40p53+ Oxa cells showed higher cell apoptosis than H1299+ p53+ Oxa cells (t=2.930, P=0.042). Conclusion: Δ40p53 isoform can bind to full-length p53, and enhance its pro-apoptotic function in tumor cells.

OBJECTIVE:To summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.METHODS:Clinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.RESULTS:Among 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.CONCLUSIONS:The choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.

患者 男性,59岁,因"前胸部疼痛"于2016年2月在山东省肿瘤医院行胸部上腹部CT检查,结果示右肺磨玻璃密度灶,考虑肺癌;胃壁略厚,腹腔淋巴结肿大,不除外转移,见图1a-1b.遂于2015年2月15日入院治疗.内镜检查见距门齿46~51 cm胃体小弯胃角巨大溃疡,见图2a;活检病理为腺癌,见图2b. 胸部PET-CT检查示右上肺病变,考虑为肺癌;胃癌,腹腔淋巴结转移,见图4. 患者家属拒绝行右肺肿物穿刺活检.诊断为原发性右肺癌(cT2N0M0),原发性胃腺癌(cT4N2M0).考虑患者肺癌及胃癌双原发,肺癌病理难以取得,胃癌会诊建议先行化疗.

Objective To study the relationship between CD11b+/ CD66b-phenotype myeloid cells and colon cancer progression and liver metastasis. Methods The transcription level, protein translation levels of CD11b, chemokine C-C motif ligand 2(CCL2)and chemokine C-C motif receptor type 2(CCR2) in colonic carcinoma tissues, colorectal cancer tissues and liver metastasis were detected by real-time PCR, Western blotting and immunohistochemistry. The co-immunoprecipitation method was used to detect the relationship between CCL2 and CCR2. Results The expression of CD11b mRNA in colorectal carcinoma and liver metastasis was higher than that in normal tissues (P<0.05). The level of CCL2 mRNA transcription and protein expression in liver metastasis was significantly higher than that in normal colonic tissues and colon cancer tissues (P<0.05). The level of CCR2 mRNA transcription and protein expression in the three were no significant difference (P>0.05). Chemokine ligand CCL2 and chemokine receptor CCR2 can be combined with each other. Conclusion CD11b phenotype myeloid cell is extensive infiltration in colon cancer and liv-er metastasis of colon cancer tissue,and possibly can promote the progression of colon cancer and liver metastasis of co-lonic carcinoma by mediating with CCL2-CCR2 axis.

OBJECTIVE:To study the correlation between the phosphorylation of keratin 18 (K18) and the autophagy and apoptosis of HCT116 cells under the effect of oxaliplatin (OXA) and investigate its possible mechanism.METHODS:HCT116 cells were transfected with empty plasmid, wild-type K18 expression plasmid and 33, 52 phosphorylation site mutated K18 (Ser33/52A) expression plasmid separately, and all cells were then treated with 60 μmol/L OXA, followed by supplementation of autophagy inhibitor 3-methyladenine (3-MA) or autophagy inducer rapamycin. FITC-conjugated annexin V and propidium iodide (PI) double staining combined with flow cytometry, calcein-AM/PI staining were used to analyze the effects of K18 and its mutants on cell apoptosis; Western blotting was performed to detect the expressions of K18 phosphorylation, autophagy related proteins microtubule associated protein 1 light chain 3 (LC3) and beclin-1.RESULTS:Transfection of Ser33/52A plasmid significantly reduced the level of K18 phosphorylation. After treated with OXA, the apoptosis rate of K18 plasmid transfected group was significantly higher than that of empty plasmid transfected group, while the apoptosis rate of Ser33/52A plasmid transfected HCT116 cells was significantly lower than that of empty plasmid or K18 plasmid transfected group. Compared with empty plasmid group, the autophagy of K18 plasmid transfected group was significantly promoted, while the autophagy in Ser33/52A plasmid transfected group was significantly inhibited.CONCLUSION:K18 overexpression enhanced the autophagy in HCT116 cells and increased its sensitivity to OXA. The decrease of K18 ser33 and ser52 phosphorylation inhibited autophagy and decreased apoptosis of HCT116 cells.