Identifying local associations in biological time series: algorithms, statistical significance, and applications.

Local associations refer to spatial-temporal correlations that emerge from the biological realm, such as time-dependent gene co-expression or seasonal interactions between microbes. One can reveal the intricate dynamics and inherent interactions of biological systems by examining the biological time series data for these associations. To accomplish this goal, local similarity analysis algorithms and statistical methods that facilitate the local alignment of time series and assess the significance of the resulting alignments have been developed. Although these algorithms were initially devised for gene expression analysis from microarrays, they have been adapted and accelerated for multi-omics next generation sequencing datasets, achieving high scientific impact. In this review, we present an overview of the historical developments and recent advances for local similarity analysis algorithms, their statistical properties, and real applications in analyzing biological time series data. The benchmark data and analysis scripts used in this review are freely available at http://github.com/labxscut/lsareview.

Regularized survival learning and cross-database analysis enabled identification of colorectal cancer prognosis-related immune genes.

Colon adenocarcinoma is the most common type of colorectal cancer. The prognosis of advanced colorectal cancer patients who received treatment is still very poor. Therefore, identifying new biomarkers for prognosis prediction has important significance for improving treatment strategies. However, the power of biomarker analyses was limited by the used sample size of individual database. In this study, we combined Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases to expand the number of healthy tissue samples. We screened differentially expressed genes between the GTEx healthy samples and TCGA tumor samples. Subsequently, we applied least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis to identify nine prognosis-related immune genes: ANGPTL4, IDO1, NOX1, CXCL3, LTB4R, IL1RL2, CD72, NOS2, and NUDT6. We computed the risk scores of samples based on the expression levels of these genes and divided patients into high- and low-risk groups according to this risk score. Survival analysis results showed a significant difference in survival rate between the two risk groups. The high-risk group had a significantly lower overall survival rate and poorer prognosis. We found the receiver operating characteristic based on the risk score was showed to accurately predict patients' prognosis. These prognosis-related immune genes may be potential biomarkers for colorectal cancer diagnosis and treatment. Our open-source code is freely available from GitHub at https://github.com/gutmicrobes/Prognosis-model.git.

Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): short-term outcomes of a multicentre randomised controlled trial.

BACKGROUND: Robotic surgery for rectal cancer is gaining popularity, but evidence on long-term oncological outcomes is scarce. We aimed to compare surgical quality and long-term oncological outcomes of robotic and conventional laparoscopic surgery in patients with middle and low rectal cancer. Here we report the short-term outcomes of this trial. METHODS: This multicentre, randomised, controlled, superiority trial was done at 11 hospitals in eight provinces of China. Eligible patients were aged 18-80 years with middle (>5 to 10 cm from the anal verge) or low (≤5 cm from the anal verge) rectal adenocarcinoma, cT1-T3 N0-N1 or ycT1-T3 Nx, and no evidence of distant metastasis. Central randomisation was done by use of an online system and was stratified according to participating centre, sex, BMI, tumour location, and preoperative chemoradiotherapy. Patients were randomly assigned at a 1:1 ratio to receive robotic or conventional laparoscopic surgery. All surgical procedures complied with the principles of total mesorectal excision or partial mesorectal excision (for tumours located higher in the rectum). Lymph nodes at the origin of the inferior mesenteric artery were dissected. In the robotic group, the excision procedures and dissection of lymph nodes were done by use of robotic techniques. Neither investigators nor patients were masked to the treatment allocation but the assessment of pathological outcomes was masked to the treatment allocation. The primary endpoint was 3-year locoregional recurrence rate, but the data for this endpoint are not yet mature. Secondary short-term endpoints are reported in this article, including two key secondary endpoints: circumferential resection margin positivity and 30-day postoperative complications (Clavien-Dindo classification grade II or higher). The outcomes were analysed according in a modified intention-to-treat population (according to the original assigned groups and excluding patients who did not undergo surgery or no longer met inclusion criteria after randomisation). This trial was registered with ClinicalTrials.gov, number NCT02817126. Study recruitment has completed, and the follow-up is ongoing. FINDINGS: Between July 17, 2016, and Dec 21, 2020, 1742 patients were assessed for eligibility. 502 patients were excluded, and 1240 patients were enrolled and randomly assigned to receive either robotic surgery (620 patients) or laparoscopic surgery (620 patients). 69 patients were excluded (34 in the robotic surgery group and 35 in the laparoscopic surgery group). 1171 patients were included in the modified intention-to-treat analysis (586 in the robotic group and 585 in the laparoscopic group). Six patients in the robotic surgery group received laparoscopic surgery and seven patients in the laparoscopic surgery group received robotic surgery. 22 (4·0%) of 547 patients in the robotic group had a positive circumferential resection margin as did 39 (7·2%) of 543 patients in the laparoscopic group (difference -3·2 percentage points [95% CI -6·0 to -0·4]; p=0·023). 95 (16·2%) of patients in the robotic group had at least one postoperative complication (Clavien-Dindo grade II or higher) within 30 days after surgery, as did 135 (23·1%) of 585 patients in the laparoscopic group (difference -6·9 percentage points [-11·4 to -2·3]; p=0·003). More patients in the robotic group had a macroscopic complete resection than in the laparoscopic group (559 [95·4%] of 586 patients vs 537 [91·8%] of 585 patients, difference 3·6 percentage points [0·8 to 6·5]). Patients in the robotic group had better postoperative gastrointestinal recovery, shorter postoperative hospital stay (median 7·0 days [IQR 7·0 to 11·0] vs 8·0 days [7·0 to 12·0], difference -1·0 [95% CI -1·0 to 0·0]; p=0·0001), fewer abdominoperineal resections (99 [16·9%] of 586 patients vs 133 [22·7%] of 585 patients, difference -5·8 percentage points [-10·4 to -1·3]), fewer conversions to open surgery (10 [1·7%] of 586 patients vs 23 [3·9%] of 585 patients, difference -2·2 percentage points [-4·3 to -0·4]; p=0·021), less estimated blood loss (median 40·0 mL [IQR 30·0 to 100·0] vs 50·0 mL [40·0 to 100·0], difference -10·0 [-20·0 to -10·0]; p<0·0001), and fewer intraoperative complications (32 [5·5%] of 586 patients vs 51 [8·7%] of 585 patients; difference -3·3 percentage points [-6·3 to -0·3]; p=0·030) than patients in the laparoscopic group. INTERPRETATION: Secondary short-term outcomes suggest that for middle and low rectal cancer, robotic surgery resulted in better oncological quality of resection than conventional laparoscopic surgery, with less surgical trauma, and better postoperative recovery. FUNDING: Shenkang Hospital Development Center, Shanghai Municipal Health Commission (Shanghai, China), and Zhongshan Hospital Fudan University (Shanghai, China).

Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.

BACKGROUND: Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. METHOD: A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. RESULTS: A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. CONCLUSION: Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

Comparison of long-term outcomes after laparoscopic-assisted and open colectomy for splenic flexure cancer.

PURPOSE: This study aimed to use propensity score matching (PSM) to compare long-term outcomes after laparoscopicassisted and open colectomy for splenic flexure cancer (SFC). METHODS: Clinical and follow-up data from 189 SFC patients undergoing colectomy at our hospital between January 2009 and January 2016 were retrospectively analyzed. According to the surgical approach employed, the patients were categorized into a laparoscopy group and an open group. The patients were matched at a ratio of 1:1 using PSM, with the match variables including gender, body mass index, clinical stage, and American Society of Anesthesiologists (ASA) score. Sixty-two patients in each group were ultimately included in this study and their short- and long-term outcomes were compared. RESULTS: In contrast to the open group, the laparoscopy group had less intraoperative blood loss, faster postoperative recovery, and shorter hospitalization duration. On day 30 after surgery, there was no statistically significant difference in the incidence of minor or major complications between the two groups. The intraoperative mortality and mortality within 30 days after surgery were all 0% in the two groups. There was no statistically significant difference in pathological results between the two groups. There was no statistically significant difference in the tumor recurrence, 5-year overall survival (OS), and 5-year disease-free survival (DFS) rates between the two groups. CONCLUSION: Laparoscopic-assisted colectomy for SFC had the same long-term outcome as open colectomy.

Detection of K-ras Mutations in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR-TK) Inhibitor in Patients with Metastatic Colorectal Cancer.

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors are useful in treating different advanced human cancers; however, their clinical efficacy varies. This study detected K-ras mutations to predict the efficacy of EGFR-TK inhibitor cetuximab treatment on Chinese patients with metastatic colorectal cancer (mCRC). A total of 87 patients with metastatic colorectal cancer were treated with cetuximab for 2-16 months, in combination with chemotherapy between August 2008 and July 2012, and tissue samples were used to detect K-ras mutations. The data showed that K-ras mutation occurred in 27/87 (31%). The objective response rates and disease control rate in K-ras wild type and mutant patients were 42% (25/60) versus 11% (3/27) (p<0.05) and 60% (36/60) versus 26% (7/27) (p<0.05), respectively. Patients with the wild-type K-ras had significantly higher median survival times and progression-free survival, than patients with mutated K-ras (21 months versus 17 months, p=0.017; 10 months versus 6 months, p=0.6). These findings suggest that a high frequency of K-ras mutations occurs in Chinese mCRC patients and that K-ras mutation is required to select patients for eligibility for cetuximab therapy. Further prospective studies using a large sample size are needed to confirm these preliminary findings.