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Circular RNAs (circRNAs) generated by back-splicing of precursor mRNAs (pre-mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis.circRNA microarray was performed with three pairs of tumor and non-tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull-down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH).Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial-mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl-CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis.These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.

The survival benefit of adjuvant radiotherapy in T4 colon cancer (CC) remains controversial, with conflicting results reported in the literature. This study aimed to explore the relationship between pretreatment carcinoembryonic antigen (CEA) level and overall survival (OS) of pT4N+ CC patients treated with adjuvant radiotherapy. Data of pT4N+ CC patients who received curative surgery between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was OS, and subgroup analysis was conducted according to pretreatment CEA level. A total of 8763 patients were eligible for our study. In the CEA-normal group, 151 patients received adjuvant radiotherapy, while 3932 patients did not. In the CEA-elevated group, 212 patients received adjuvant radiotherapy, while 4468 patients did not. In general, adjuvant radiotherapy was associated with better OS in pT4N+ CC patients (HR = 0.846, 95% CI = 0.733–0.976, P = 0.022 ). Intriguingly, only patients with an elevated pretreatment CEA level gained a survival benefit from adjuvant radiotherapy (HR = 0.782; 95% CI = 0.651–0.939; P = 0.008 ) while those with a normal pretreatment CEA level did not (HR = 0.907; 95% CI = 0.721–1.141; P = 0.403 ). Multivariable Cox regression analysis demonstrated that adjuvant radiotherapy was an independent protective factor in pT4N+ CC patients with an elevated pretreatment CEA level. Pretreatment CEA levels could serve as a potential biomarker to screen pT4N+ CC patients who would benefit from adjuvant radiotherapy.

Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log‐rank test and multivariate Cox regression analysis according to EMT‐related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high‐risk patients who need an intensive follow‐up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.

Tumor size has an effect on decision making for the treatment rectal cancer. Transanal local excision can be selected to remove rectal cancer with favorable histopathological features. It is generally recognized that the risk of lymph node involvement and distant metastases increases as the tumor enlarges. However, the majority of the studies classified patients into two groups using concrete value as a cutoff point. The coarse classification was not sufficient to reveal a correlation between the tumor size and lymph node status or distant metastases across the full range of sizes examined. Between 1988 and 2015, a total of 77,746 patients were diagnosed with first primary rectal cancer who had not received neoadjuvant therapy. These subjects were identified using the Surveillance, Epidemiology and End Results (SEER) database. The association between tumor size, lymph node status, distant metastases and cancer-specific mortality was investigated. Tumor size was examined as a continuous (1-30 mm) and categorical variable (11 size groups; 10-mm intervals). A non-linear correlation between increasing tumor size and the prevalence of lymph node involvement was observed, while a near-positive correlation between tumor size and distant metastases was presented. In addition, the 5-year and 10-year rates of rectal cancer-specific mortality were increased as the tumor enlarged. For small tumors (under 30 mm), a positive correlation was noted between tumor size and lymph node involvement. The clinical value of the tumor size should be reevaluated by exact classification.

Previous studies developed prognostic signatures largely depended on transcriptome profiles. The purpose of our present study was to develop a proteomic signature to optimize the evaluation of prognosis of colon cancer patients. The proteomic data of colon cancer patient cohorts were downloaded from The Cancer Proteome Atlas (TCPA). Patients were randomized 3:2 to train set and internal validation set. Univariate Cox regression and lasso Cox regression analysis were performed to identify the prognostic proteins. A four-protein signature was developed to divide patients into a high-risk group and low-risk group with significantly different survival outcomes in both train set and internal validation set. Time-dependent receiver-operating characteristic at 1 year demonstrated that the proteomic signature presented more prognostic accuracy [area under curve (AUC = 0.704)] than the American Joint Commission on Cancer tumor-node-metastasis (AJCC-TNM) staging system (AUC = 0.681) in entire set. In conclusion, we developed a proteomic signature which can improve prognostic accuracy of patients with colon cancer and optimize the therapeutic and follow-up strategies.

Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

The prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported.A total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response).Of the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients' prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2).TRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.

Preoperative chemoradiation followed by surgery has been recommended as a standard treatment for patients with stage II/III rectal cancer. However, the optimal sequencing of radiotherapy for metastatic rectal cancer remains unclear. Between 2004 and 2014, patients diagnosed with metastatic rectal cancer who underwent the resection of primary site and received radiotherapy were retrospectively selected using the Surveillance, Epidemiology, and End Results (SEER) database. The propensity score matching analyses were used to lessen the effects of confounding factors including age, sex, race, marital status, serum carcinoembryonic antigen level, histologic type, differentiation status, tumor size, T stage, N stage and resection of the distant lesions. The cancer-specific survival (CSS) were compared based on the sequencing of radiotherapy. Ultimately, 686 matched pairs were formed for comparison of preoperative versus postoperative radiotherapy. The 5-year CSS estimates were 33.4% (95% CI: 28.9%-37.9%) and 26.8% (95% CI: 22.7%-30.9%) for patients underwent preoperative radiotherapy followed by resection of primary lesion and postoperative radiotherapy after surgery, respectively. Patients underwent preoperative radiotherapy had better CSS as compared to patients received postoperative radiotherapy (p

So far, many existing evidences indicate that microRNAs (miRNA) are closely associated with the tumorigenesis and progression of various tumors. It has been reported that miR-1301-3p is abnormally expressed in several malignant tumors. However, the role of miR-1301-3p in gastric cancer (GC) remains unclear and is worth studying. Through qRT-PCR, the expression of miR-1301-3p and SIRT1 were detected in GC tissues and cells. The cell proliferation and cell cycle were measured through CCK-8 assay and clone formation assay. Dual luciferase reporter assay was used to determine the target of miR-1301-3p. Though tumorigenesis assay, we monitored the effect of miR-1301-3p on GC cell growth in vivo. miR-1301-3p was upregulated in GC tissues and cells in our study. Overexpression of miR-1301-3p accelerated GC cell proliferation, cell cycle progression and tumorigenesis. Notably, altering the expression miR-1301-3p caused deregulation of Cyclin D1, CDK4, c-Myc and P21. Furthermore, SIRT1 was the direct target of miR-1301-3p by luciferase reporter assay. After transfecting with miR-1301-3p inhibitor, we found that knockdown of SIRT1 could enhance the ability of proliferation. Our results identify miR-1301-3p as a novel potential therapeutic target that is associated with the tumorigenesis and progression of gastric cancer.

Background Stage IV colorectal cancer (CRC) patients are heterogeneous with distinctive clinicopathologic features and prognosis. Radical resection of primary tumor and distant metastases is associated with improved survival outcomes in metastatic CRC. The value of palliative primary tumor resection is controversial. The present study explored which subgroups benefited more from primary tumor resection in metastatic CRC. Methods Between 2004 and 2015, patients with metastatic CRC were identified using the surveillance, epidemiology, and end results (SEER) database. Uni- and multivariable Cox regression analysis were performed to identify factors associated with decreased cancer-specific mortality. The subgroups were divided based on the independent prognostic factors. Results Age, marital status, race, serum CEA, histologic type, differentiation, tumor location, surgery of primary or metastatic lesion, site of metastases, number of metastatic sites, chemotherapy and radiotherapy were identified as independent prognostic factors. Patients with non-white race, normal serum CEA, non-signet ring cell carcinoma, well or moderate differentiation, surgery of metastases, isolated liver metastasis, single metastasis, receiving chemotherapy or radiotherapy presented more survival benefit from primary tumor resection. Conclusion Subgroup of metastatic CRC optimizes decision-making and selected patients will benefit more from primary tumor resection.

A metabolic disorder is considered one of the hallmarks of cancer. Multiple differentially expressed metabolic genes have been identified in colon cancer (CC), and their biological functions and prognostic values have been well explored. The purpose of the present study was to establish a metabolic signature to optimize the prognostic prediction in CC. The related data were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, and Gene Expression Omnibus (GEO) combined with GSE39582 set, GSE17538 set, GSE33113 set, and GSE37892 set. The differentially expressed metabolic genes were selected for univariate Cox regression and lasso Cox regression analysis using TCGA and GTEx datasets. Finally, a seventeen-gene metabolic signature was developed to divide patients into a high-risk group and a low-risk group. Patients in the high-risk group presented poorer prognosis compared to the low-risk group in both TCGA and GEO datasets. Moreover, gene set enrichment analyses demonstrated multiple significantly enriched metabolism-related pathways. To sum up, our study described a novel seventeen-gene metabolic signature for prognostic prediction of colon cancer.

BackgroundBased on a prognostic scoring system (P score) proposed by us recently, this retrospective large population-based and propensity score-matched (PSM) study focused on predicting the survival benefit of adjuvant CT in stage II disease.MethodsPatients diagnosed with stage II colon cancer (N = 73397) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 1988 and December 31, 2005 and divided into the CT and non-CT groups. PSM balanced the patient characteristics between the CT and non-CT groups.ResultsThe magnitude of CSS improvement among patients treated with adjuvant CT was significantly associated with the P score, score 8 [hazard ratio (HR) = 0.580, 95% confidence interval (CI) = 0.323–1.040, P = 0.067] was associated with a much higher increased CSS benefit among patients treated with adjuvant CT as compared to score 2* (*, including scores 0, 1, and 2; HR = 1.338, 95% CI = 1.089–1.644, P = 0.006).ConclusionsHigh P scores were demonstrated to be associated with superior survival benefit of adjuvant CT. Therapy decisions of adjuvant CT in stage II colon cancer could be tailored on the basis of tumor biology, patient characteristics and the P score.

Epigenetic factors play a critical role in carcinogenesis by imparting a distinct feature to the chromatin architecture. The present study aimed to develop a novel epigenetic signature for evaluating the relapse-free survival of colon cancer patients. Public microarray datasets were acquired from the Gene Expression Omnibus databases: GSE39582, GSE17538, GSE33113, and GSE37892 set. Patients from GSE39582 set were randomized 1:1 into training and internal validation series. Patients were divided into high-risk and low-risk groups in training series based on a set of 11 epigenetic factors (p < .001). The good reproducibility for the prognostic value of the epigenetic signature was confirmed in the internal validation series (p < .001), external validation series (a combination of GSE17538 set, GSE33113 set, and GSE37892 set; p = .018), and entire series (p < .001). Furthermore, a nomogram, which integrated the epigenetic signature, pathological stage, and postoperative chemotherapy, was developed based on the GSE39582 set. The time-dependent receiver operating characteristic curve at 1 year demonstrated that the comprehensive signature presented superior prognostic value than the pathological stage. In conclusion, an epigenetic signature, which could be utilized to divide colon cancer patients into two groups with significantly different risk of relapse, was established. This biomarker would aid in identifying patients who require an intensive follow-up and aggressive therapeutic intervention.

Additional file 2: Figure S2. X-tile analyses of DFS were performed to determine the optimal cut-off valuesfor basophils count.

Additional file 4: Table S1. Comparison of baseline characteristics of the whole cohort by the serum basophil level. Table S2. OS of colorectal cancer after incorporation of serum basophil count level into conventional AJCC TNM staging system.

Additional file 1: Figure S1. Receiver operating characteristic curves for immune/inflammation-relatedbiomarkers in blood routine examination, including basophil, white blood cell (WBC), platelet, neutrophil, lymphocyte, monocyte and eosinophil.

Additional file 3: Figure S3. Kaplan–Meier (a). DFS and (b). OS curves of the serum basophil count level.

Background Accumulating evidence demonstrated immune/inflammation-related implications of basophils in affecting tissue microenvironment that surrounded a tumor, and this study aimed to elucidate the clinical value of serum basophil count level. Methods Between December 2007 and September 2013, 1029 patients diagnosed with stage I–III CRC in Fudan University Shanghai Cancer Center meeting the essential criteria were identified. The Kaplan–Meier method was used to construct the survival curves. Several Cox proportional hazard models were constructed to assess the prognostic factors. A simple predictor (CB classifier) was generated by combining serum basophil count and serum carcinoembryonic antigen (CEA) level which had long been accepted as the most important and reliable prognostic factor in CRC. Results The preoperative basophils count

Aim This study aimed to investigate circumferential resection margin (CRM) as a prognostic factor for long‐term oncologic survival after rectal cancer surgery. Methods Patients diagnosed with malignant rectal cancer between 1 January 2010 and 31 December 2014, from the Surveillance, Epidemiology, and End Results (SEER) program were identified for this study. The patients were divided into five CRM groups to compare the baseline characteristics and assess cancer‐specific survival (CSS): 0‐1 mm, 1.1‐2.0 mm, 2.1‐5.0 mm, 5.1‐10.0 mm, and >10 mm. The main endpoint was CSS. Results Circumferential resection margin ≤1 mm was independently associated with 99% increased risk of cancer‐specific mortality in rectal cancer [hazard ratio (HR) = 1.990, 95% confidence interval (CI) = 1.613‐2.454, P

Qi Liu,1,2 Dakui Luo,1,2 Sanjun Cai,1,2 Qingguo Li,1,2 Xinxiang Li1,2 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Aim: This study focused on improving the American Joint Committee on Cancer TNM staging system and demonstrated an improvement in prognostic accuracy and clinical management of colon cancer using the P–TNM staging system. Patients and methods: Eligible patients (N=56,800) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 2010, and December 31, 2014. The P-stage (P0 or P1) was assigned to each patient based on age at diagnosis, tumor grade, and tumor size. The outcome of interest was cancer-specific survival (CSS). The Cox proportional hazards regression analyses were used to identify independent prognostic factors and analyze the CSS probabilities of patients with colon cancer having different P–TNM stages, respectively. Results: A total of 29,627 patients were assigned to P0-stage and 27,173 patients were assigned to P1-stage. The P1-stage was associated with a 98.1% increased risk of cancer-specific mortality (hazard ratio =1.981, 95% confidence interval =1.891–2.076, P

This study aimed to improve the American Joint Committee on Cancer (AJCC) Tumor Node Metastases (TNM) staging system and demonstrate the improvement in prognostic accuracy and clinical management guidance in colon cancer using the novel prognostic score (P score). Eligible patients were identified using the Surveillance, Epidemiology, and End Results database. A P score (based on age, tumor size, and tumor grade) was assigned to each patient. The Cox proportional hazards regression analyses were performed to identify independent factors associated with prognosis. The Kaplan–Meier survival curves were used to analyze the prognosis of patients with colon cancer with different P scores. The TNM staging system was compared with the P score in stages I–IV by calculating the concordance index. The multivariate Cox analysis indicated that a higher P score was independently associated with a higher risk of cancer-specific mortality. The Kaplan–Meier survival curves showed that the survival benefit gradually increased as the P score decreased. The concordance index rose from 0.5, 0.593, 0.633, and 0.551 of AJCC TNM staging system to 0.709, 0.651, 0.691, and 0.623 of P score in stages I–IV, respectively. The P score was an independent prognostic factor of colon cancer and had a much better prognostic accuracy than the AJCC TNM staging system in all patients with colon cancer. It may help in identifying patients with high-risk stage II colon cancer who were candidates for adjuvant therapy and differentiating patients with stage III colon cancer for adjuvant therapy.

In spite of the unique advantages of minimally invasive treatment, laparoscopic surgery is not recommended in T4 colon cancer patients with the concern of technical feasibility and suboptimal oncologic outcomes. We used the database of our center to reevaluate laparoscopic surgery's value in T4 colon cancer and compared with open surgery in both short- and long-term outcomes.We conducted a retrospective and propensity score-matched study of pathological T4 colon cancer patients who received laparoscopic surgery or open surgery from March 2011 to August 2015.A total of 411 pathological T4 colon cancer patients were identified. Propensity score matching (PSM) resulted in 86 patients in laparoscopic group and 86 patients in open group. Our study showed longer operation time, less blood loss and less length of postsurgical stay compared with open surgeries (167 ± 56 min vs. 111 ± 50.1 min, P 0.001; 72 ± 61.5 mL vs. 113 ± 113.9 mL, P = 0.004; 7.3 ± 2.1 days vs. 7.9 ± 2.1 days, P = 0.046, respectively). 7 (8.2%) patients underwent conversions to open surgery. 5-years of DFS and OS showed no statistic difference between the two groups. The 1-, 3-, and 5-years OS rates were 89.4%, 77.5% and 73.2% for laparoscopic surgery and 95.2%, 82.7% and 73.9% for open surgery (P = 0.618). The 1-, 3-, and 5-years OS rates were 89.5%, 77.2% and 61.7% for laparoscopic surgery and 91.7%, 75.3% and 66.8% for open surgery (P = 0.903).Our analysis demonstrates that there is no statistic difference in short- and long-oncologic outcomes in our center and it is a reliable evidence to support the clinical application of laparoscopic surgery in T4 colon cancer patients. Still, considering the lack of randomized controlled trails, conducting large prospective multi-center population-based studies is not only required, but also pressing.

// Dakui Luo 1, * , Younan Wang 1, * , Xiangkun Huan 1, * , Chi Huang 1, * , Chao Yang 2 , Hao Fan 1 , Zekuan Xu 1 , Li Yang 1 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 2 Liver Transplantation Center of the First Affiliated Hospital and Key Laboratory on Living Donor Liver Transplantation, Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu, China * These authors have contributed equally to this work Correspondence to: Li Yang, email: pwkyangli@163.com Keywords: gastric cancer, TRIM59, synonymous variant, genotype, Chinese population Received: July 13, 2016 Accepted: November 22, 2016 Published: December 21, 2016 ABSTRACT Tripartite motif 59 (TRIM59) is a novel oncogenic driver in gastric cancer (GC) that is implicated in disease progression as well as dismal survival. Genetic variants in peculiar gene are likely candidates for conferring hereditary susceptibility. The role of TRIM59 polymorphism in predicting the risk of malignant diseases and its relevance to TRIM59 expression have not been discussed. Using a HapMap tagSNPs approach, we screened three tag TRIM59 single nucleotide polymorphisms (SNPs) (rs1141023G>A, rs7629A>G, rs11706810T>C) which were genotyped in 602 GC patients and 868 healthy controls. Our study provided convincing result that carries of variant rs1141023A allele markedly increased GC risk (P=0.006). In comparison with the GG homozygotes, the variant GA heterozygotes demonstrated 1.50-fold elevated risk of GC (p=0.014, 95% confidence interval [CI] = 1.09–2.08). Subjects who carried the (GA+AA) genotypes of rs1141023 were associated with remarkable increased GC risk compared with the common genotype (P = 0.013, adjusted OR = 1.50, 95% CI = 1.09–2.05). Further stratified analyses displayed that the relationship between mutant genotype of rs1141023 and GC risk was more profound in male individuals. Intriguingly, there is no significant distinction of TRIM59 mRNA expression between rs1141023GA genotype and GG genotype in 44 normal gastric tissues. Taken together, our results suggest that rs1141023 polymorphism contributes to increased predisposition to GC and thus may be responsible for predicting early GC.

In contrast to normal differentiated cells that depend on aerobicoxidation for energy production, cancer cells use aerobic glycolysis as the main source (Warburg's effect). The M2 splice isoform of pyruvate kinase (PKM2) is the key regulator for the aerobic glycolysis, high expression of PKM2 contributes to the aerobic glycolysis, promotes the growth of tumors. In the present study, we found that PKM2 was highly expressed in gastric cancer (GC) tissues and had a strongly inverse correlation with the expression of microRNA-let-7a (miR-let-7a). Furthermore, we found that the overexpression of miR-let-7a markedly suppressed the proliferation, migration, and invasion of GC cells by down-regulating the expression of PKM2. MicroRNAs (miRNAs) are important regulators play key roles in tumorigenesis and tumor progression. Although previous reports showed that let-7 family members act as tumor suppressors in many cancers. The specific regulatory mechanism of miR-let-7a to PKM2 in gastric cancer is still unclear. In this study, we revealed that miR-let-7a function as the antitumor and gene regulatory effects of PKM2 in GC cells.

// Xiang Ma 1, * , Chi Huang 1, * , Dakui Luo 1, * , Younan Wang 1, * , Ran Tang 1 , Xiangkun Huan 1 , Yi Zhu 2 , Zekuan Xu 1 , Ping Liu 3 , Li Yang 1 1 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2 Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, Nanjing, China 3 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Li Yang, email: pwkyangli@163.com Keywords: gastric cancer, TINCR, polymorphism, genotype Received: February 14, 2016 Accepted: November 06, 2016 Published: November 23, 2016 ABSTRACT Tissue differentiation-inducing non-protein coding RNA (TINCR) is required for normal epidermal differentiation. TINCR is also strongly overexpressed in human gastric cancer (GC) and contributes to carcinogenesis and tumor progression. However, the association between TINCR polymorphisms and the risk of any diseases, such as GC, remains unknown. In the present study, the tag single nucleotide polymorphisms rs8113645, rs2288947, rs8105637, and rs12610531 were analyzed in 602 patients with GC and 602 age- and sex-matched controls. Polymorphisms were genotyped using TaqMan technology. Carriers of variant rs8113645 and rs2288947 alleles indicated reduced risks of GC ( p = 0.003 and 0.037, respectively). A allele genotypes of rs8113645 and G allele genotypes of rs2288947 (rs8113645 GA and AA; rs2288947 AG and GG) were also significantly associated with decreased GC risk ( p < 0.05). Stratification analysis displayed that the correlations between GC risk and variant genotypes of both rs8113645 and rs2288947were more evident in younger individuals, men, nonsmokers, and individuals from rural areas. We also demonstrated that rs8113645 GA+AA genotype carriers had lower TINCR mRNA expression levels compared with common genotype in both normal and GC tissues ( p < 0.05). These results suggest that long non-coding RNA TINCR polymorphisms may be implicated in GC development.

Qi Liu,1,2,* Peng Lian,1,2,* Dakui Luo,1,2 Sanjun Cai,1,2 Qingguo Li,1,2 Xinxiang Li1,2 1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China *These authors contributed equally tothis work Aim: This study assessed the combination of carcinoembryonic antigen (CEA) with the American Joint Committee on Cancer (AJCC) TNM staging system, aiming to improve the AJCC TNM staging system, in terms of prognostic accuracy and clinical management of rectal cancer. Methods: Eligible patients (N=22,132) were selected from the Surveillance, Epidemiology, and End Results database between January 1, 2004, and December 31, 2010. Patients with elevated CEA levels were designated as “C1 stage” and those with normal CEA amounts as “C0 stage”. The outcome of interest was cancer-specific survival (CSS). Cox proportional hazards regression analyses and Kaplan–Meier curves were used to identify independent prognostic factors and analyze the odds of CSS in patients with rectal cancer in different C and TNM stages, respectively. Results: C1 stage was associated with a 61.0% risk increase in cancer-specific mortality (HR=1.610, 95% CI=1.219–1.705, P

Purpose: Gastric adenosquamous carcinoma (ASC) is a rare pathological type with poorly understood clinicopathological features. The purpose of this study is to identify the characteristics of gastric ASC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2000 to 2014), patients with ASC (N=93) or adenocarcinoma (AC) (N=41794) of the stomach were included. The epidemiology, tumor features, treatment, and outcomes between these two groups were compared. Results: The incidences of ASC from 1983 to 2014 [annual percentage change (APC) = -3.5%, 95% confidence interval (CI) -4.9 to -2.1] and AC from 1973-2014 [APC = -1.8%, 95%CI -2.0 to -1.6] decreased over time. Compared to AC cases, patients with ASC were more likely to present poor differentiation (74.2% vs 52.4%) and later summary stage (distant: 46.2% vs 33.6%) or later T stage (T4: 15.1%% vs 9.0%). Besides, the proportion of patients with distant metastasis (33.3% vs 23.9%), and chemotherapy (44.1% vs 34.0%) in ASC group was higher. The Kaplan-Meier analyses showed ASC cases had worse overall survival (OS) (p=0.017) than that of AC after propensity score matching (PSM), but not the cancer-specific survival (CSS) (p=0.849). The further subgroup analyses suggested no statistical significance between gastric ASC patients and AC patients for CSS. The multivariate cox proportional hazard analyses indicated that patients with distant summary stage (HR=2.11, p=0.014), no surgery (HR=2.22, p=0.016), and no/unknown chemotherapy (HR=3.33, p

Background: The present study analyzed the nonbiological factors (NBFs) together with the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system to generate a refined, risk-adapted stage for the clinical treatment of colon cancer. Methods: Eligible patients (N = 28,818) with colon cancer between 1 January 2010 and 31 December 2014, were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves and Cox proportional hazards regression, analyzed the probabilities of cancer-specific survival (CSS) in patients with colon cancer, with different NBF-TNM stages. Results: Insurance status, marital status, and median household income were significant prognostic NBFs in the current study (p &lt, 0.05). The concordance index of NBF-TNM stage was 0.857 (95% confidence interval (CI) = 0.8472&ndash, 0.8668). Multivariate Cox analyses, indicated that NBF1-stage was independently associated with a 50.4% increased risk of cancer-specific mortality in colon cancer (p &lt, 0.001), which increased to 77.1% in non-metastatic colon cancer. NBF0-stage improved in CSS as compared to the NBF1-stage in the respective stages (p &lt, 0.05). Conclusions: The new proposed NBF-stage was an independent prognostic factor in colon cancer. Effect of NBFs on the survival of colon cancer necessitates further clinical attention. Moreover, the incorporation of NBF-stage into the AJCC TNM staging system is essential for prognostic prediction, and clinical guidance of adjuvant chemotherapy in stage II and III colon cancer.

Background: The effect of adjuvant chemotherapy on stage II colon cancer remains constantly controversial. Recently, however, several studies have reported the definite survival benefit of adjuvant chemotherapy (ACT) in T4 disease (stage IIB and IIC) among stage II colon cancer patients. The following study investigates the efficacy of ACT in patients with poorly differentiated stage IIA colon cancer. Methods: The first cohort of eligible patients (N=38384) diagnosed with stage IIA colon cancer was selected from the Surveillance, Epidemiology, and End Results database (SEER) between January 1, 2004, and December 31, 2010. Cox proportional hazards regression analyses and Kaplan-Meier curves were used to evaluate the survival benefit following ACT. Our findings were also evaluated in Fudan University Shanghai Cancer Center (FUSCC) cohort form FUSCC database. Results: In SEER cohort, poorly differentiated or undifferentiated tumor grade was associated with 21.5% increased cancer-specific mortality in patients who did not receive ACT (HR=1.215, 1.004-1.469, P=0.045, using poorly differentiated or undifferentiated ACT as a reference). In FUSCC cohort, poorly differentiated or undifferentiated tumor grade was also associated with increased DFS in patients who received ACT (HR = 0.160, 95% CI = 0.017-1.505, P=0.109, using poorly differentiated or undifferentiated, non-ACT as a reference). In addition, patients with poorly differentiated or undifferentiated tumor who did not receive ACT had a higher risk of distant metastasis and recurrence compared to patients who received ACT (log-rank P=0.027 and 0.119, respectively). Conclusion: ACT decreased the recurrence rate and distant metastasis rate thus improving prognosis for poorly differentiated or undifferentiated stage IIA colon cancer.

Purpose: Radiotherapy (RT) has been reported to effectively palliate many symptoms of patients with metastatic rectal cancer (mRC). The objective of this study was to evaluate the survival benefit of RT in mRC. Methods: A retrospective population-based cohort study was performed using the Surveillance, Epidemiology, and End Results Program (SEER) database. Patient baseline demographic characteristics between the RT and no-RT groups were compared using Pearson chi-square tests. The outcome of interest was cause-specific survival (CSS). Propensity score (PS) matching and Cox proportional hazards regression analyses were performed to evaluate the prognostic power of variables on CSS. Results: A total of 8851 patients with mRC were identified in the SEER database. Multivariable Cox regression analysis showed that RT was a protective factor in mRC (hazard ratio [HR]= 0.702, 95% confidence interval [CI]=0.665-0.741, p