Aim: To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. Materials & methods: Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group. Cancerous tissue gene expression profiles were detected by chip technology. Valuable biomarkers were screened by bioinformatic analysis. Immunohistochemical analysis was performed to characterize the pattern of HOXB8 and KLK11 expression. HOXB8 and KLK11 signal probe values were analyzed using receiver operating characteristic analysis. Results: There were differentially expressed genes in the two groups. HOXB8 and KLK11 proteins were observed in the nucleus and on the outside of the cancer cells, respectively. Their prediction accuracies were 79.9 and 76.7%, respectively. Conclusion: HOXB8 and KLK11 may be classified as valuable biomarkers, as they can predict the effects of FOLFOX4 chemotherapy in primary advanced colorectal cancer patients.
To establish a nomogram to predict long-term survival in non-metastatic colorectal cancer patients.A retrospective analysis was conducted in patients with non-metastatic colorectal cancer who underwent radical surgery in the Department of Colorectal Surgery of Affiliated Union Hospital of Fujian Medical University between January 2000 and December 2014. Univariate and multivariate analyses on disease-free survival (DFS) were performed using the Cox proportional regression model. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the probability for DFS. Concordance index was applied in predictive evaluation of the nomogram and calibration curves were drawn to test the nomogram's prediction and actual observation of the 5-year DFS rate. The predictive ability of nomogram was compared with AJCC-7 staging system.A total of 2 641 patients were identified. The median age was 59.3 years old, and 60.3% of cases were men. The number of patients with TNM stage 0, I(, II( and III( was 96, 505, 923 and 1043, respectively. The most common tumor site was the rectum, accounting for 43.2%. A total of 413 (15.6%) patients underwent neoadjuvant treatment. The most common gross type of tumor was ulcerative type, accounting for 79.5%. The 3- and 5-year DFS rate was 85.8% and 79.8%, respectively. Based on the Cox proportional regression model, the following six factors were independently associated with reduced DFS rate and were selected for the nomogram: older age, higher pathologic T stage, higher pathologic N stage, higher preoperative serum CEA level, infiltrative gross type and perineural invasion. The results of the nomogram showed that the score of T0, T1, T2, T3 and T4 stage was 0, 2.2, 3.9, 4.1 and 6, respectively, and the score of N0, N1 and N2 was 0, 3.8 and 9.3, respectively. For gross type, the score of expanding type, ulcerative type and infiltrative type was 6, 9 and 10, respectively. The score of perineural invasion was 5.2. Higher scores were added to older age and higher CEA level. The total scores were calculated by taking the sum of the points from all predictors. Higher total score was associated with poor DFS. The prognostic nomogram differentiated well and showed a concordance index of 0.718, which was better than AJCC-7 staging system (concordance index=0.683). Also, the calibration of nomogram predictions was good.A nomogram based on 6 independently prognostic factors to predict long-term survival in non-metastatic colorectal cancer patients is established successfully. The nomogram can be conveniently used to facilitate the accurate individualized prediction of DFS rates in patients with non-metastatic colorectal cancer.
To introduce the diagnosis and the treatment of the long-segment bowel stenosis above the anastomosis and bowel obstruction caused by the radiation-induced pelvic wall and bowel fibrosis.Between January 2008 and June 2014, 468 patients with rectal carcinoma underwent sphincter-preserving operation after neoadjuvant chemoradiotherapy in Fujian Medical University Union Hospital. Among 241 patients without postoperative anastomotic leakage, anastomosis stenosis, local recurrence and small bowel obstruction, severe pelvic and bowel fibrosis with obstruction during follow-up was found in 14 patients(SFO group). Associated data of these 14 patients were retrospectively collected. Clinical and image characteristics, and treatment outcomes of these 14 patients were analyzed and compared to those of other 227 patients without fibrosis and obstruction (control group).Compared to control group, SFO group had lower BMI(19.7±2.3 vs. 22.5±3.2, P=0.000), higher ratio of male (92.9% vs. 63.9%, P=0.039) and smoking patients(78.6% vs. 32.2%, P=0.001), shorter preoperative distance from lower edge of tumor to anal verge [(4.9±0.7) cm vs. (5.7±1.4) cm, P=0.043), and longer time from the end of radiation to operation [(9.4±2.3) week vs. (8.1±1.7) week, P=0.024). The largest thickness of the bilateral obturator internus increased significantly after chemoradiotherapy (left side: P=0.030, right side: P=0.020) as compared to pre-chemoradiotherapy on MR image. Patients of SFO group received corresponding treatments according to the status of bowel stricture, and the outcomes were all satisfactory.Reconstructed rectum stricture can be caused by the radiation-induced fibrosis of pelvic wall soft tissue and proximal colon. Severe stricture can be treated with corresponding methods to relieve symptoms.
Identifying key causal genes is critical for unraveling the genetic basis of complex economic traits, yet it remains a formidable challenge. The advent of large-scale sequencing data and computational algorithms, such as transcriptome-wide association studies (TWASs), offers a promising avenue for identifying potential causal genes. In this study, we harnessed the power of TWAS to identify genes potentially responsible for milk production traits, including daily milk yield (MY), fat percentage (FP), and protein percentage (PP), within a cohort of 100 buffaloes. Our approach began by generating the genotype and expression profiles for these 100 buffaloes through whole-genome resequencing and RNA sequencing, respectively. Through comprehensive genome-wide association studies (GWAS), we pinpointed a total of seven and four single nucleotide polymorphisms (SNPs) significantly associated with MY and FP traits, respectively. By using TWAS, we identified 55, 71, and 101 genes as significant signals for MY, FP, and PP traits, respectively. To delve deeper, we conducted protein-protein interaction (PPI) analysis, revealing the categorization of these genes into distinct PPI networks. Interestingly, several TWAS-identified genes within the PPI network played a vital role in milk performance. These findings open new avenues for identifying potentially causal genes underlying important traits, thereby offering invaluable insights for genomics and breeding in buffalo populations.
To explore the efficacy of radiotherapy combined with surgery for locally advanced rectal mucinous adenocarcinoma.Clinical data of patients with locally advanced rectal mucinous adenocarcinoma (T3-4 and/or N+) diagnosed by postoperative pathology from 1992 to 2013 were retrieved from the US Surveillance, Epidemiology, and End Results (SEER) database. Patients with local excision only, tumor biopsy or combined organ excision and incomplete follow-up information were excluded. All the enrolled patients were divided into three groups according to different treatments, including surgery alone (SA) group, preoperative radiotherapy combined with surgery (RT+S) group and surgery combined with postoperative radiotherapy (S+RT) group. The extracted data included basic data of patients and tumor, treatment status, and follow-up results. The χ² test was used to compare the count data. Kaplan-Meier method was used to draw the survival curve and calculate the survival rate. The survival was analyzed and compared by Log-rank test. The R language 2.8.1 was used to match the patients as 1:1 pairing through the propensity score matching (PSM). The matching variables included gender, age at diagnosis, year at diagnosis, ethnicity, degree of tissue differentiation, TNM stage, depth of invasion, making the baseline data of subgroups comparable. The Cox proportional hazard model was used for multivariate analysis of prognostic factors.A total of 2 149 patients with locally advanced rectal mucinous adenocarcinoma were enrolled in the study, including 1 255 males (58.4%) and 894 females (41.6%). There were 706 patients (32.9%) in the SA group, 772 patients (35.9%) in the RT+S group and 671 patients (31.2%) in the S+RT group. In SA, RT+S and S+RT groups, the median overall survival time was 39, 85, and 74 months respectively; the 5-year overall survival (OS) rate was 38.7%, 56.5%, and 55.2% respectively; the median cancer-specific survival (CSS) time was 86, 127, and 111 months respectively, and the 5-year CSS rate was 53.7%, 62.2% and 60.7% respectively. In comparison among the 3 groups, the 5-year OS rate and CSS rate in the SA group were significantly lower than those in the RT+S group and S+RT group (all P<0.001); the 5-year OS rate and CSS rate between RT+S group and S+RT group were not significantly different (P=0.166 and 0.392,respectively). After the baseline data of subgroups were corrected through PSM, the 5-year OS rate and CSS rate in the SA group (n=375) were significantly lower than those in the RT+S group (n=375)(OS:40.1% vs. 54.5%, P<0.001; CSS:54.3% vs. 63.3%, P=0.023). The 5-year OS rate and CSS rate in the SA group (n=403) were also lower than those in the S+RT group (n=403) (OS:37.4% vs. 54.7%,P<0.001;CSS:51.6% vs. 61.0%,P=0.031). The 5-year OS rate and CSS rate between RT+S group (n=363) and S+RT group (n=363) were not significantly different (OS:51.7% vs. 55.5%, P=0.789; CSS:57.7% vs. 60.5%, P=0.484). Cox multivariate analysis showed that radiotherapy (HR=0.845, 95%CI: 0.790 to 0.903, P=0.001) was an independent prognostic factor for OS of locally advanced rectal mucinous adenocarcinoma; radiotherapy (HR=0.907, 95% CI: 0.835 to 0.985, P=0.021) was also an independent prognostic factor affecting CSS in patients with locally advanced rectal mucinous adenocarcinoma.As compared with surgery alone, surgery combined with preoperative or postoperative radiotherapy is beneficial to the long-term survival of patients with locally advanced rectal mucinous adenocarcinoma.
Objective To detect global gene expression in colorectal cancer patients with simultaneous liver metastases (mCRC) and screen a valuable biomarker model to predict the sensitivity of FOLFOX4 chemotherapy.Methods There are totally 30 cases from primary mCRC patients who have undergone FOLFOX4 chemotherapy were collected.Their chemotherapy effects were evaluated and the patients were divided into chemotherapy sensitive group (13 cases) and non-sensitive group (17 cases).Cancerous tissue gene expression profiles were detected by using chip technology.Two groups with differentially expressed genes based on gene expression profiles were screened by cluster analysis and significance analysis of microarrays (SAM).Thirty differentially expressed genes were screened out which had | Score(d)|≥2 and Fold Change≥2 or ≤0.5.The differentially expressed gene probe signals were transformed into log ratio values using Biweight algorithm to calculate area under curve (AUC),sensitivity,and specificity.The most predictable and accurate differential expression genes would be selected to value the efficiency of chemotherapy.Results The first seven predictive ability genes,NKX2-3,FXYD6,transforming growth factor beta1 induced transcript 1 (TGFB1I1),ACTG2,ANPEP,KLK11 and homeobox B8 (HOXB8) combined into a prediction model with the forecasting accuracy being 93.3％.Conclusion The combined seven genes prediction model may be classified as valuable and important model for assessing chemotherapy sensitivity of mCRC patients who will receive FOLFOX4 chemotherapy.
Key words:
Colorectal cancer; FOLFOX4; Chemotherapy sensitivity; Gene expression profile
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