Intravoxel incoherent motion diffusion-weighted imaging and dynamic contrast-enhanced MRI for predicting parametrial invasion in cervical cancer.

PURPOSE: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients. METHODS: A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters. RESULTS: Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78-27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49-29.10; P = 0.01), f (OR 5.12; 95% CI 1.23-21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19-17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25-19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%. CONCLUSION: The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Short-term Outcomes of Laparoscopy-Assisted vs Open Surgery for Patients With Low Rectal Cancer: The LASRE Randomized Clinical Trial.

Importance: The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. Objective: To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. Design, Setting, and Participants: This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Interventions: Eligible patients were randomized to receive either laparoscopic or open surgery. Main Outcomes and Measures: The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. Results: A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. Conclusions and Relevance: In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT01899547.

Screening and validation of a novel T stage-lymph node ratio classification for operable colon cancer.

BACKGROUND: Lymph node ratio (LNR) has advantages in predicting prognosis compared with American Joint Committee on Cancer (AJCC) pathological N stage. However, the prognostic value of a novel T stage-lymph node ratio (TLNR) classification for colon cancer combining LNR and pathological primary tumor stage (T stage) is currently unknown. METHODS: We included 62,294 patients with stage I-III colon cancer from the Surveillance, Epidemiology, and End Results Program as a training cohort. External validation was performed in 3,327 additional patients. A novel LNR stage was established and combined with T stage in a novel TLNR classification. Patients with similar survival were grouped according to T and LNR stages, with T1LNR1 as a reference. RESULTS: We developed a novel TLNR classification as follows: stages I (T1LNR1-2, T1LNR4), IIA (T1LNR3, T2LNR1-2, T3LNR1), IIB (T1LNR5, T2LNR3-4, T3LNR2, T4aLNR1), IIC (T2LNR5, T3LNR3-4, T4aLNR2, T4bLNR1), IIIA (T3LNR5, T4aLNR3-4, T4bLNR2), IIIB (T4aLNR5, T4bLNR3-4), and IIIC (T4bLNR5). In the training cohort, the novel TLNR classification had better prognostic discrimination (area under receiver operating characteristic curve, 0.621 vs. 0.608, two-sided P<0.001), superior model-fitting ability for predicting overall survival (Akaike information criteria, 561,129 vs. 562,052), and better net benefits compared with the AJCC 8th tumor/node/metastasis classification. Similar results were found in the validation cohort for predicting both overall and disease-free survival. CONCLUSIONS: This novel TLNR classification may provide better prognostic discrimination, model-fitting ability, and net benefits than the AJCC 8th TNM classification, for potentially better stratification of patients with operable stage I-III colon cancer; however, further studies are required to validate the novel TLNR classification.

Diagnostic Value of Combined Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Diffusion Tensor Imaging in Predicting Parametrial Infiltration in Cervical Cancer.

Objective: This study sought to determine the diagnostic value of combined intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) in predicting parametrial infiltration (PMI) in patients with cervical cancer. Materials and Methods: We enrolled 65 patients with cervical cancer confirmed by radical hysterectomy (25 PMI-negative and 40 PMI-positive) who underwent IVIM and DTI pretreatment. The parameters of IVIM (ADC, D, D ∗ , and f) and DTI (average diffusion coefficient (DCavg) and fractional anisotropy (FA)) were recorded by two observers. All parameter differences were tested, and the receiver operating characteristic (ROC) curves were generated to estimate the diagnostic performance of significant metrics and their combinations. Results: Compared to the PMI-negative group, the PMI-positive group had significantly lower D (0.632 ± 0.017 vs. 0.773 ± 0.024, p < 0.001) and lower FA (0.073 ± 0.002 vs. 0.085 ± 0.003, p=0.003). The area under the ROC curve (AUC) of D and FA was 0.801 and 0.726, respectively, and the combination of D and FA improved the AUC to 0.931, with a sensitivity and specificity of 80.0% and 97.5%, respectively. Conclusion: D and FA values could be used to help diagnose PMI in patients with cervical cancer. The combination of IVIM and DTI was more valuable than either option alone.

Diagnosis of Cervical Cancer With Parametrial Invasion on Whole-Tumor Dynamic Contrast-Enhanced Magnetic Resonance Imaging Combined With Whole-Lesion Texture Analysis Based on T2- Weighted Images.

Purpose: To evaluate the diagnostic value of the combination of whole-tumor dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and whole-lesion texture features based on T2-weighted images for cervical cancer with parametrial invasion. Materials and Methods: Sixty-two patients with cervical cancer (27 with parametrial invasion and 35 without invasion) preoperatively underwent routine MRI and DCE-MRI examinations. DCE-MRI parameters (Ktrans, Kep, and Ve) and texture features (mean, skewness, kurtosis, uniformity, energy, and entropy) based on T2-weighted images were acquired by two observers. All parameters of parametrial invasion and non-invasion were analyzed by one-way analysis of variance. The diagnostic efficiency of significant variables was assessed using receiver operating characteristic analysis. Results: The invasion group of cervical cancer demonstrated significantly higher Ktrans (0.335 ± 0.050 vs. 0.269 ± 0.079; p < 0.001), lower energy values (0.503 ± 0.093 vs. 0.602 ± 0.087; p < 0.001), and higher entropy values (1.391 ± 0.193 vs. 1.24 ± 0.129; p < 0.001) than those in the non-invasion group. Optimal diagnostic performance [area under curve [AUC], 0.925; sensitivity, 0.935; specificity, 0.829] could be obtained by the combination of Ktrans, energy, and entropy values. The AUC values of Ktrans (0.788), energy (0.761), entropy (0.749), the combination of Ktrans and energy (0.814), the combination of Ktrans and entropy (0.727), and the combination of energy and entropy (0.619) were lower than those of the combination of Ktrans, energy, and entropy values. Conclusion: The combination of DCE-MRI and texture analysis is a promising method for diagnosis cervical cancer with parametrial infiltration. Moreover, the combination of Ktrans, energy, and entropy is more valuable than any one alone, especially in improving diagnostic sensitivity.

Diagnostic Performance of MR Imaging-based Features and Texture Analysis in the Differential Diagnosis of Ovarian Thecomas/Fibrothecomas and Uterine Fibroids in the Adnexal Area.

RATIONALE AND OBJECTIVES: To investigate the value of MRI-based features and texture analysis (TA) in the differential diagnosis between ovarian thecomas/fibrothecomas (OTCA/f-TCAs) and uterine fibroids in the adnexal area (UF-iaas). MATERIALS AND METHODS: This retrospective study included 16 OTCA/f-TCA and 37 UF-iaa patients who underwent conventional MRI and DWI between August 2014 and September 2018. Three-dimensional TA was performed with T2-weighted MRI. The clinical, MRI-based and texture features were compared between OTCA/f-TCAs and UF-iaas. Multivariate logistic regression analysis was used for filtering the independent discriminative features and constructing the discriminating model. ROCs were generated to analyse MRI-based features, texture features and their combination for discriminating between the two diseases. RESULTS: Six imaging-based features (ipsilateral ovary detection, arterial period enhancement, lesion components, peripheral cysts, "whorl signs", mean ADCs) and six texture features (Histogram-energy, Histogram-entropy, Histogram-kurtosis, GLCM-energy, GLCM-entropy, and Haralick correlation) were significantly different between OTCA/f-TCAs and UF-iaas (p < 0.05). Multivariate analysis of the MRI-based features revealed that arterial period enhancement (OR = 0.104), peripheral cysts (OR = 16.513), and whorl signs (OR = 0.029) were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p < 0.05). Multivariate analysis of the texture features showed that Histogram-energy and GLCM-energy were independent features for discriminating between OTCA/f-TCAs and UF-iaas (p < 0.05). The area under the curve of imaging-based diagnosis was 0.85, and the combination of imaging-based diagnosis and TA improved the area under the curve to 0.87, with higher accuracy, specificity and sensitivity of 86%, 92%, and 84%, respectively (p < 0.05). CONCLUSIONS: MRI-based features can be useful in differentiating OTCA/f-TCAs from UF-iaas. Furthermore, combining imaging-based diagnosis and TA can improve diagnostic performance.

RIG-I: a multifunctional protein beyond a pattern recognition receptor

It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations. While in hepatocellular carcinoma and acute myeloid leukemia, RIG-I acts as a tumor suppressor through either augmenting STAT1 activation by competitively binding STAT1 against its negative regulator SHP1 or inhibiting AKT-mTOR signaling pathway by directly interacting with Src respectively. These new findings suggest that RIG-I plays more diverse roles in various cellular life activities, such as cell proliferation and differentiation, than previously known. Taken together, the function of RIG-I exceeds far beyond that of a pattern recognition receptor.

Diagnostic potential of serum exosomal colorectal neoplasia differentially expressed long non-coding RNA (CRNDE-p) and microRNA-217 expression in colorectal carcinoma.

In this study, we investigated the diagnostic potential of serum exosomal colorectal neoplasia differentially expressed (CRNDE-p) long coding RNA and microRNA-217 in colorectal carcinoma (CRC). We detected high CRNDE-p and low miR-217 levels in exosomes released by multiple CRC cell lines into culture media as well as in sera from CRC xenograft mice and CRC patients. Conversely, we observed lower CRNDE-p and higher miR-217 levels in serum exosomes from post-chemotherapy than from pre-chemotherapy patient samples. The area under curve (AUC) value for the serum exosomal CRNDE-p and miR-217 combination was higher than CRNDE-p or miR-217 alone. Moreover, high CRNDE-p and low miR-217 serum exosomal levels correlated with advanced clinical stages (III/IV), tumor classification (T3/T4), and lymph node or distant metastasis. Thus combined evaluation of serum exosomal CRNDE-p and miR-217 levels show diagnostic and prognostic potential for CRC patients.

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND/AIMS: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. METHODS: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/ß-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of ß-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. RESULTS: In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/ß-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. CONCLUSIONS: The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/ß-catenin signaling through binding miR-217 competitively.

Very Early Colorectal Anastomotic Leakage within 5 Post-operative Days: a More Severe Subtype Needs Relaparatomy.

Early anastomotic leakage (AL), usually defined as leakage within 30 post-operative days, represents a severe entity. However, mounting evidence has indicated that majorities of leakage occur within one week after surgery, making late AL rarity. Here we analyzed 101 consecutive colorectal AL, all of which occurred within 30 post-operative days, during Jan 2013 and Dec 2015 in cancer hospital of Fudan University. AL occurring within 5 post-operative days was defined as very early AL (vE-AL). We evaluated risk factors of vE-AL compared with non-vEAL and correlated with post-leakage peritonitis and need of relaparatomy. We found that AL occurred at median time of 7 days after surgery. 23 cases were vE-AL. Reconstruction of post-peritoneum for mid-low rectal carcinoma significantly reduced incidence of vE-AL compared with non-vE-AL (p = 0.042). Patients with vE-AL was associated with presence of peritonitis (p = 0.031), the latter significantly correlated with increased re-operation rate (p = 6.8E-13). Besides, patients with vE-AL trended to correlate with increased re-operation rate after leakage (p = 0.088). In concludsion, vE-AL occurring within 5 post-operative days represents a severe subtype associated with general peritonitis and need of relaparatomy.

Core value of laparoscopic colorectal surgery.

Since laparoscopy was first used in cholecystectomy in 1987, it has developed quickly and has been used in most fields of traditional surgery. People have now accepted its advantages like small incision, quick recovery, light pain, beauty and short hospital stays. In early times, there are still controversies about the application of laparoscopy in malignant tumor treatments, especially about the problems of oncology efficacy, incision implantation and operation security. However, these concerns have been fully eliminated by evidences on the basis of evidence-basis medicine. In recent years, new minimally invasive technologies are appearing continually, but they still have challenges and may increase the difficulties of radical dissection and the risks of potential complications, so they are confined to benign or early malignant tumors. The core value of the laparoscopic technique is to ensure the high quality of tumor's radical resection and less complications. On the basis of this, it is allowed to pursue more minimally invasive techniques. Since the development of laparoscopic colorectal surgery is rapid and unceasing, we have reasons to believe that laparoscopic surgery will become gold standard for colorectal surgery in the near future.

Laparoscopic vs open abdominoperineal resection in the multimodality management of low rectal cancers.

AIM: To evaluate the safety and feasibility of laparoscopic abdominoperineal resection compared with the open procedure in multimodality management of rectal cancer. METHODS: A total of 106 rectal cancer patients who underwent open abdominoperineal resection (OAPR) were matched with 106 patients who underwent laparoscopic abdominoperineal resection (LAPR) in a 1 to 1 fashion, between 2009 and 2013 at Fudan University Shanghai Cancer Center. Propensity score matching was carried out based on age, gender, pathological staging of the disease and administration of neoadjuvant chemoradiation. Data regarding preoperative staging, surgical technique, pathological results, postoperative recovery and complications were reviewed and compared between the LAPR and OAPR groups. Perineal closure around the stoma and pelvic floor reconstruction were performed only in OAPR, not in LAPR. Therefore, abdominoperineal resection procedure-specific surgical complications including parastomal hernia and perineal wound complications were compared between the open and laparoscopic procedure. Regular surveillance of the two cohorts was carried out to gather prognostic data. Disease-free survival was analyzed using Kaplan-Meier estimate and log-rank test. Subgroup analysis was performed in patients with locally advanced disease treated with preoperative chemoradiation followed by surgical resection. RESULTS: No significant difference was found between the LAPR group and the OAPR group in terms of clinicopathological features. The operation time (180.8 ± 47.8 min vs 172.1 ± 49.2 min, P = 0.190), operative blood loss (93.9 ± 60.0 mL vs 88.4 ± 55.2 mL, P = 0.494), total number of retrieved lymph nodes (12.9 ± 6.9 vs 12.9 ± 5.4, P = 0.974), surgical complications (12.3% vs 15.1%, P = 0.549) and pathological characteristics were comparable between the LAPR and OAPR group, respectively. Compared with OAPR patients, LAPR patients showed significantly shorter postoperative analgesia (2.4 ± 0.7 d vs 2.7 ± 0.6 d, P < 0.001), earlier first flatus (57.3 ± 7.9 h vs 63.5 ± 9.2 h, P < 0.001), shorter urinary drainage time (6.5 ± 3.4 d vs 7.8 ± 1.3 d, P < 0.001), and shorter postoperative admission (11.2 ± 4.7 d vs 12.6 ± 4.0 d, P = 0.014). With regard to APR-specific complications (perineal wound complications and parastomal hernia), there were no significant differences between the two groups. Similar results were found in the 26 pairs of patients administered neoadjuvant chemoradiation in subgroup analysis. During the follow-up period, no port site recurrences were observed. CONCLUSION: Laparoscopic abdominoperineal resection for multidisciplinary management of rectal cancer is safe, and is associated with earlier recovery and shorter admission time in combination with neoadjuvant chemoradiation.

Standard chemotherapy with cetuximab for treatment of colorectal cancer.

AIM: To review and assess the evidence related to cetuximab treatment in metastatic colorectal cancer (mCRC) with regard to KRAS status. METHODS: PubMed, EMBASE, Cochrane database and American Society of Clinical Oncology meeting abstracts were searched for randomized controlled trials (RCTs) reporting the effect of KRAS status on efficacy of chemotherapy regimen with or without cetuximab in mCRC. Baseline information such as sex and age was summarized from the included studies. Hazard ratios of progression-free survival (PFS) and overall survival (OS) as well as objective response based on KRAS status were extracted for analysis. RESULTS: A total of 8 RCTs with 6780 patients were included. The combined analysis showed that cetuximab failed to improve the OS and PFS in patients with mCRC. However, in subgroup analysis, the pooled data showed that addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve OS and PFS in wild-type KRAS mCRC patients, but not in patients with mutant-type KRAS. The addition of cetuximab increased the incidence of adverse events such as diarrhea, rash, skin toxicity/rash, and nausea and vomiting. There was no significant publication bias existing in the included studies. CONCLUSION: The clinical benefit of cetuximab was only confirmed in patients with wild-type KRAS. KRAS status could be considered a biomarker of efficacy of cetuximab.

RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer cell lines.

Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial response of patients to these regimes and the severe peripheral neuropathy toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for oxaliplatin sensitivity to select suitable patients who benefit from these treatments. In present work, 21 CRC cell lines with different sensitivities to oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell lines were correlated to their response to oxaliplatin. Bioinformatics analysis suggested that expression of 58 genes was correlated, negatively or positively, to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly enriched in small molecules biochemistry, Wnt/ß-catenin signaling and EMT pathways. The latter two pathways were predicted to be activated in oxaliplatin-resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their expression levels were actually closely correlated to their response to oxaliplatin, in line with the biocomputation prediction. Taken together, our work might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines and therapeutic targets for combinational therapy with oxaliplatin.

Laparoscopic segmental colectomy for colonic lymphangiomas: a definitive, minimally invasive surgical option.

Colonic lymphangioma is an unusual benign malformation. We herein describe two cases. A 36-year-old woman was admitted with one year of intermittent abdominal pain; colonoscopy, abdominopelvic computed tomography and endoscopic ultrasonography (EUS) revealed enlarged cystic masses at the ascending colon. In another 40-year-old man, colonoscopy and EUS revealed an asymptomatic lobulated cystic mass with four small sessile polyps at the sigmoid colon. Both patients underwent laparoscopic segmental colectomy. Both masses were histologically confirmed as cystic lymphangiomas, and the patients were discharged without complications. The management of colonic lymphangioma depends on the individual situation; close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5 cm in diameter. Surgical intervention can be considered for larger lesions or in patients who develop complication risks. Laparoscopic segmental colon resection may be recommended to excise relatively large submucosal lesions because it is a definitive, minimally invasive intervention with a fast postoperative recovery.

High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer.

OBJECTIVE: This study sought to investigate the role of the long noncoding RNA MALAT1 in the prognosis of stage II/III colorectal cancer (CRC) patients. METHODS: The expression of MALAT1 was evaluated in cancer tissues from 146 stage II/III CRC patients undergoing radical resection and 23 paired normal colonic mucosa samples using quantitative real-time reverse transcriptase PCR. Differences in the expression of MALAT1 between 23 CRC and paired normal colonic mucosa samples were analysed with the Wilcoxon test. Relationships between the expression level of MALAT1, patient clinicopathological parameters and disease-free survival (DFS) and overall survival (OS) were analysed using the univariate Kaplan-Meier method and the multivariate COX regression model. RESULTS: The MALAT1 levels in cancerous tissues were 2.26 times higher than those measured in noncancerous tissues, and this difference was statistically significant (P = 0.0004). Based on their expression level of MALAT1, the patients were divided into a high MALAT1 expression group (n = 73) and a low expression group (n = 73). Patients with tumours harbouring higher expression of MALAT1 showed a significantly worse prognosis with a hazard ratio (HR) of 2.863 (95% CI, 1.659 to 4.943; P < 0.001) for DFS and 3.968 (95% CI, 1.665 to 9.456; P = 0.002) for OS. Furthermore, patients with perineural invasion demonstrated significantly worse DFS (HR = 3.459, 95% CI 2.008 to 5.957; P < 0.001) and OS (HR = 3.750, 95% CI 1.743 to 8.069; P = 0.001) than those without perineural invasion. Multivariate analyses indicated that MALAT1 expression and perineural invasion were two independent prognostic risk factors for patients with CRC. CONCLUSION: The expression of MALAT1 is upregulated in CRC tissues, and a higher expression level of MALAT1 might serve as a negative prognostic marker in stage II/III CRC patients.

Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and ß-arrestin pathways.

The CXC chemokine receptor 7 (CXCR7) has been reported to be involved in cell growth, metastasis and apoptosis in certain cancers. However, the function and molecular mechanisms of CXCR7 in human colorectal cancer (CRC) are still undefined. In the present study, sixty-eight cases of CRC tissues and corresponding adjacent non-cancer tissues (ANCT) were collected, and the expression of CXCR7 was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, CXCR7 gene was silenced by small hairpin RNA-mediated lentiviral vector (Lv-shCXCR7), by transfection into human CRC cells (SW480 and HT-29). The levels of p-ERK, ß-arrestin, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and caspase-3 (CAS-3) were detected by western blotting. Cell proliferative activities and invasive capability were respectively measured by MTT and Transwell assays. Cell apoptosis was analyzed by flow cytometry. The results demonstrated that CXCR7 expression was significantly upregulated in CRC tissues compared with the ANCT (54.4 vs. 36.8%, P=0.041), and correlated with Dukes staging and depth of invasion (P=0.007; P=0.002). Silencing of CXCR7 gene suppressed cell proliferation and invasion, and induced cell apoptosis in CRC cells with decreased expression of p-ERK, ß-arrestin, PCNA and MMP-2 but increased expression of CAS-3. The tumor volumes in the SW480 subcutaneous tumor models treated with Lv-shCXCR7 were significantly smaller than those of the negative control (NC) and PBS groups (P<0.01). In conclusion, our findings indicate that upregulation of CXCR7 expression is associated with tumor invasion, and silencing of the CXCR7 gene represses the development of CRC cells through ERK and ß-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of CRC.

RNA-seq reveals determinants for irinotecan sensitivity/resistance in colorectal cancer cell lines.

Irinotecan is a topoisomerase I inhibitor approved worldwide as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). Although irinotecan showed significant survival advantage for patients, a relatively low response rate and severe adverse effects demonstrated the urgent need for biomarkers searching to select the suitable patients who can benefit from irinotecan-based therapy and avoid the adverse effects. In present work, the irinotecan response (IC50 doses) of 20 CRC cell lines were correlated with the basal expression profiles investigated by RNA-seq to figure out genes responsible for irinotecan sensitivity/resistance. Genes negatively or positively correlated to irinotecan sensitivity were given after biocomputation, and 7 (CDC20, CTNNAL1, FZD7, CITED2, ABR, ARHGEF7, and RNMT) of them were validated in two CRC cell lines by quantitative real-time PCR, several of these 7 genes has been proposed to promote cancer cells proliferation and hence may confer CRC cells resistance to irinotecan. Our work might provide potential biomarkers and therapeutic targets for irinotecan sensitivity in CRC cells.