Colon Rectal Cancer Research Articles

The surgical management of large bowel obstruction in patients with left colon and rectal cancer – a retrospective study

The optimal surgical attitude towards obstructed left colon and upper rectal cancer remains elusive, one of the main postoperative endpoints being to avoid the most dreaded complication of this type of procedures - the anastomotic leakage. Material and methods: We conducted a retrospective analysis of all patients with left colon and rectal cancer admitted and having emergency surgery performed in the surgical departments of the University County Hospital of Craiova, Romania, between 2001 and 2018. The timeline analysis showed an increasing interest for single-stage resection and anastomosis in the second decade (2011-2018) compared to the first decade of the study (28% vs. 11.2%). Results: The incidence of anastomotic leak for these types of procedures remained higher than for the two-stage procedure (15% vs. 4.8%), similar to the overall postoperative morbidity (30.3% vs. 20%) and mortality (3% vs. 1.1%). Postoperative morbidity and anastomotic leak rate were statistically higher in the single stage procedure group when compared with the two-stage procedure (p <0.05). Conclusions: Deciding between single-stage resection with anastomosis and a two-stage procedure requires a careful patient selection due to the relatively high risk of anastomotic leak in this specific category of patients.

Awareness about Risk Factors of Colorectal Cancer among Employees at Minia University

Background: Colorectal cancer (CRC) is cancer that begins in the colon or rectum, depending on where it is located, these cancers may also be called colon cancer or rectal cancer, and it is the third most common tumor in Egypt in males after urinary bladder and lymphohematopoietic malignancies and ranks fifth in females following bladder cancers. Aim of the study: The present study aimed to assess awareness about risk factors of colorectal cancer among employees at Minia University. Design: A cross-sectional design was used for this study. Setting: This study was conducted at five faculties in Minia University (Faculty of Medicine, Faculty of Early Childhood Education, Faculty of Tourism and Hotels, Faculty of Science, and Faculty of Nursing) randomly selected. Sample: The study was conducted on 365 employees from the selected faculties to participate in this study over six months from July 2020 to December 2020. Tool of data Collection Data were collected through a structured questionnaire, consisted of two parts: Part I: personal data of employees. Part II: Bowel / colorectal cancer awareness assessment. Results: More than half (56.7 %) of the study participants had poor CRC awareness. Education, family history, occupation, and residence were the significant factors related to participants' awareness (p-value 0.00, 0.006, 0.001, 0.001 respectively). Conclusion: This study concluded that the majority of participants had inadequate awareness about colorectal cancer risk factors. There is a highly statistically significant difference as regards the level of awareness of participants and their level of education, family history of CRC, occupation, and residence. Recommendations: Encourage health practitioners to disseminate information to the general public on safe lifestyles and cancer prevention and conducting further researches to investigate barriers and misconceptions about CRC screening programs.

Current Therapeutic Strategies in BRAF-Mutant Metastatic Colorectal Cancer.

Around 8–12% of patients with advanced colon rectal cancer (CRC) present with BRAF alterations, in particular V600E mutation, which is associated with right-side, poorly differentiated and mucinous type tumors. The presence of BRAF mutation (BRAF-mt) has been identified as a hallmark of poor prognosis and treatment optimization in this patient subgroup is an important goal. Currently, the standard of care is an aggressive strategy involving triplet chemotherapy and anti-VEGF agents, but new therapeutic approaches are emerging. Very promising results have been obtained with targeted therapy combinations, such as anti-BRAF agents plus anti-EGFR agents. Furthermore, around 60% of BRAF-mt patients show a strong association with high microsatellite instability (MSI-H) and immune checkpoint inhibitors could represent the new standard of care for this subgroup. The focus of this review is to summarize current strategies for BRAF-mt CRC treatment and highlight new therapeutic options.

Asbestos Fibers and Ferruginous Bodies Detected by VP-SEM/EDS in Colon Tissues of a Patient Affected by Colon-Rectum Cancer: A Case Study

The aim of this work was to inspect the presence of asbestos fibers in colon tissue from a patient, with history of indirect exposure to asbestos and affected by colon cancer, who underwent surgery. Variable pressure scanning electron microscopy, coupled with energy dispersive spectroscopy (VP-SEM/EDS), was used for identification of inorganic fibers and for their morphological—chemical characterization. Fresh tissue samples from both, healthy area close to the neoplasia and from the neoplastic regions, were separately digested to eliminate the biological matrix. The precipitate was analyzed by VP-SEM/EDS, identifying in samples from healthy tissue asbestos bodies and small asbestos fibers, and in samples from neoplastic tissue long fibers of asbestos, free from covering. A quantification of the asbestos bodies and the free fibers in the two type of specimens is proposed. Moreover, to locate the fibers in the biological medium, histological sections from the colon of the same patient were also examined. Free asbestos fibers appeared concentrated in the tissue bridge between the healthy and the neoplastic areas. Immuno-histochemical investigation performed on the neoplasia seems to exclude a role of microsatellite instability in the carcinogenesis process, suggesting an influence of the fibers.

A steep increase in healthcare seeking behaviour in the last months before colorectal cancer diagnosis

BackgroundTimely recognition of colorectal cancer related symptoms is essential to reduce time to diagnosis. This study aims to investigate the primary healthcare use preceding a colorectal cancer diagnosis.MethodsFrom a cohort of linked cancer and primary care data, patients diagnosed with primary colorectal cancer in the period 2007–2014 were selected and matched to cancer-free controls on gender, birth year, GP practice and follow-up period. Primary healthcare use among colorectal cancer cases before diagnosis was compared with matched cancer-free controls. Mean monthly number of GP consultations and newly prescribed medication was assessed in the year before index date (diagnosis date for cases). Results were stratified by colorectal cancer site: proximal colon cancer, distal colon cancer and rectal cancer.ResultsA total of 6,087 colorectal cancer cases could be matched to four cancer-free controls (N = 24,348). While mean monthly number of GP consultation were stable through the year among cancer-free controls, a statistical significant increase was seen among colorectal cancer cases in the last 4–8 months before diagnosis. Proximal colon cancer cases showed the longest time interval of increased mean monthly number of GP consultations. This increase was largely driven by a consultation for malignant neoplasm colon/rectum. The number patients receiving a newly prescribed medication was stable around 120 per 1,000 persons per month until 8 months before index date for proximal colon cancer cases, 4 months before index date for distal colon cancer cases and 3 months for rectal cancer cases. This increase was mainly driven by the prescription of laxatives drugs.ConclusionAn increase in the healthcare seeking behaviour of colorectal cancer patients prior to diagnosis was seen. The longest period of increased GP consultations and newly prescribed medication was seen among patients diagnosed with proximal colon cancer. This can be explained by the difficultly to diagnose proximal colon cancer given the more subtle signs compared to distal colon cancer and rectal cancer. Therefore, faster diagnosis for this specific tumour subtype may only be possible when clear clinical signs and symptoms are present.

Detection and Clinical Value of Circulating Tumor Cells as an Assisted Prognostic Marker in Colorectal Cancer Patients.

BackgroundCirculating tumor cells (CTCs) are cells that have been shed into the vasculature from a primary tumor and circulate in the bloodstream. It has been suggested that detecting CTCs could help the clinician to detect early metastasis or recurrence more effectively. This trial sets out to assess the detection and clinical value of CTCs as an assisted prognostic marker in patients with colon cancer and rectal cancer.MethodsA prospective cohort of patients with colorectal cancer (CRC) was enrolled from July 2015 to February 2018 in Shanghai Minimally Invasive Surgery Center, Shanghai, China. In this study, 149 patients with CRC were enrolled and underwent surgical treatment. There were 79 cases of colon cancer and 70 cases of rectal cancer, including 93 males and 56 females. To investigate the correlativity and clinical value of CTCs, the patients were statistically analyzed in different subgroups: colon cancer group vs rectal cancer group, and left hemicolon cancer group vs right hemicolon cancer group.ResultsThe results of analysis comparing CTC counts and clinical pathological features in colon and rectal cancer indicated that with increased tumor stage, the number of CTCs also increased, with significant statistical differences. CTC counts in patients with colon and rectal cancer showed positive correlations with TNM staging (P=0.001, 0.013, respectively), T staging (P=0.021, 0.001), N staging (P=0.014, 0.035) and M staging (P=0.018, 0.203). Detection of serum biomarkers in CTC-positive and CTC-negative groups indicated a significantly increasing expression in the CTC-positive group. To confirm the correlations between CTCs and histoembryological differences, analysis was conducted with the patients in two subgroups: left hemicolon cancer group and right hemicolon cancer group. The results showed that the positive rate of CTCs increased in both groups with the increase in tumor stage. The survival analysis indicated that there was a steep gradient in survival in the follow-up period, particularly in the CTC-positive group (P=0.000). Risk assessment curves showed that the change escalated more rapidly in the CTC-positive group. Furthermore, with the increase in T stage, changes in the survival curve and risk curve escalated more rapidly in the CTC-positive group.ConclusionIt was confirmed that in the left hemicolon cancer group, a much higher coincidence rate could be found on CTC-positive rate and clinicopathological features, than in the right hemicolon cancer group. The sensitivity of CTCs may be related to the histoembryological location of the tumor, lymphatic metastasis and the depth of infiltration. Monitoring CTCs may have value in evaluating clinical staging and estimating clinical prognosis.

Socioeconomic gaps over time in colorectal cancer survival in England: flexible parametric survival analysis

BackgroundDespite persistent reports of socioeconomic inequalities in colorectal cancer survival in England, the magnitude of survival differences has not been fully evaluated.MethodsPatients diagnosed with colon cancer (n=68 169) and rectal...

Responsibility of immune microenvironment for poor response to immune checkpoint inhibitors in CRC patients with KRAS mutation.

e15588 Background: The clinical trial Keynote 177 is a breakthrough research in colon rectal cancer (CRC), however, the results of subgroups revealed that immunotherapy did not benefit more than chemotherapy in patients with KRAS mutation. Here we assessed characteristics of tumor immune microenvironment in patients with or without KRAS mutation, to find out the underlying mechanisms that prevent KRAS-mutated CRC patients from benefiting from immunotherapy. Methods: Tumor tissue samples of 77 CRC patients were collected from Janary 2019, several kinds of immune cells including CD8+ T cells, M1/M2 tumor associated macrophages (TAM), CD56bright NK cells and CD56dim NK cells in the tumor tissue were evaluated by multiple fluorescence immunohistochemistry (mIHC), and expression of PD-L1 were detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. In addition, gene mutation was detected by means of next generation squesing (NGS). All these detections were performed in a College of American Pathologists (CAP)-certified and Clinical Laboratory Improvement Amendments (CLIA)-accredited lab for gene mutation analysis (3D Medicines Inc.,Shanghai, China). Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS,Inc.). Results: According to whether KRAS is mutated, these 77 patients were divided into two groups, KRAS wild type (WT) (n = 49) and KRAS mutation group (n = 28). There was no significant difference in the CD8+T cells infiltrated in tumor tissue of KRAS WT and KRAS mutation samples, however, less CD8+ T cells were found in stroma of tumor tissue of KRAS WT samples than in KRAS mutation. What’s more, both the ratio of M1:M2 and CD56dim NK: CD56bright NK cells in the tumor tissues of KRAS WT were significantly higher than in KRAS mutation samples(p &lt; 0.05). No significant difference was found between two groups, while higher MSI-H proportion was found in KRAS mutation group than in KRAS WT (33.4% and 12.5%, respectively). The proportion of positive PD-L1expression (TPS≥1) in both groups is very low, especially, proportion of strong positive (TPS≥50). Conclusions: The different response to immune checkpoint inhibitors therapy for CRC patient with or without KRAS mutation mainly associated with factors of TIME, not only CD8+T cells, but tumor associated macrophages and different sub-population of NK cells should be put into consideration.

Description of asymptomatic cancer patients with COVID-19 infection: Experience of the ACHOCC-19 study in one Latin American country.

e18761 Background: Cancer has been described as a risk factor for worse prognosis in people with Covid-19. However, there are few studies informing on the characteristics of cancer patients that have asymptomatic SARS-cov2 infection. The ACHOCC-19 study included asymptomatic patients. Methods: Analytical cohort study of patients with cancer and SARS-cov2 infection in Colombia. From April 1 to October 31, 2020, we collected data on demographic and clinical variables related to cancer and COVID-19 infection. We describe the characteristics and outcomes of patients who had no symptoms of COVID19. Association between outcomes and prognostic variables was analyzed using logistic regression models. Results: We included 742 patients, of which 205 (27.6%) were asymptomatic. Of these 62.2% were older than 61 years, 66% were women, 1.42% were smokers. The most frequent malignancy was breast cancer (25%), followed by colon-rectum (14.6%), sarcoma/soft tissues (5.66%) and lung cancer (5.19%). Patients were more likely to be asymptomatic if they had fewer comorbidities (0-1 comorbidities: 84% asymptomatic, 2 comorbidities: 10.85%, more than 2 comorbidities: 5.15%). 90.5% lived in urban areas and 53.37% had low income. 35.4% of patients had metastatic disease, 8.7% had progressive cancer, 40% had stable disease or partial response. No patient had an ECOG PS of 4 or more, and only 1.91% had ECOG 3. In logistic regression analysis statistically significant associations for having symptomatic disease included: man, presence of 1, 2 or &gt; 2 comorbidities, ECOG 1,2 or 3 and cancer in progression. On the other hand, the statistically significant ORs for having asymptomatic disease were age between 18 and 30 years old, cancer in remission and receiving non-cytotoxic treatment. Table sumarizes ORs and their respective 95% CIs of the variables adjusted in the logistic regression model. Conclusions: In our stumdy, cancer patients had a higher probability of asymptomatic COVID-19 infection if they were women, between the ages of 18 and 30 years, had cancer in remission , ECOG 0 and no comorbidities. This is the first cohort of patients with cancer and asymptomatic covid 19 with a significant sample size in Latin America.[Table: see text]

The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats.

Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50mg/kg (i.p.) for 24weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group. Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.

SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and includes colon cancer (CC) and rectal cancer (RC). Regarding CC, the development of novel molecular biomarkers for the accurate diagnosis and prognosis, as well as the identification of novel targets for therapeutic intervention, are urgently needed. SRY-related high-mobility group box 9 (SOX9), a transcription factor, is involved in development, and has been associated with the progression of human cancer. However, its underlying clinical and functional effects in CRC have not been fully understood. Therefore, the present study aimed to evaluate the clinical and functional relevance of SOX9 expression in CC. The expression of SOX9 in tumor tissues was evaluated in 97 biopsies from Mexican patients with CC with early-stage I and II disease by immunohistochemistry (IHC). In addition, SOX9 silencing in the HCT116 cell line was performed using specific small interfering RNAs, while downregulation efficiency was verified by reverse transcription-quantitative PCR and immunofluorescence. Spheroid-formation assay was carried out using ultra-low attachment plates. The IHC results showed that SOX9 was upregulated in patients with stage II (91%) and advanced T3 stage (67%) CC. Interestingly, higher SOX9 expression was associated with clinical stage, tumor size and tumor location. Furthermore, increased SOX9 expression was found in relapsed cases with local tumors; however, it was not associated with increased survival probability. Additionally, functional analysis indicated that SOX9 silencing significantly attenuated the sphere-formation capability of HCT116 cells. The present study was the first to evaluate the expression levels of SOX9 in Mexican patients diagnosed with early-stage CC. The aforementioned findings indicated that high SOX9 expression could play an important role in tumorigenesis and be associated with advanced T-stages of clinical-stage II patients, but not with relapse-free survival.

Primary Anastomosis Versus End-Ostomy in Left-Sided Colonic and Proximal Rectal Cancer Surgery in the Elderly Dutch Population: A Propensity Score Matched Analysis

BackgroundPrimary anastomosis (PA) in left-sided colorectal cancer (CRC) surgery in elderly patients is disputed. The aim of our study was to evaluate the differences in postoperative outcomes after left-sided CRC surgery in elderly patients in The Netherlands, comparing patients with PA and those who underwent end-ostomy (EO).MethodPatients aged ≥ 75 years with stage I–III left-sided CRC, diagnosed and surgically treated in 2015–2017 were selected from the Netherlands Cancer Registry (n = 3286). Postoperative outcomes, short-term (30-, 60-, and 90-day) mortality and 3-year overall and relative survival were analyzed, stratified by surgical resection with PA versus EO. Propensity score matching (PSM) and multivariable logistic regression analysis were conducted.ResultsPatients with higher age, higher American Society of Anesthesiologists classification and higher tumor stage, a perforation, ileus or tumor located in the proximal rectum, and after open or converted surgery were more likely to receive EO. No difference in anastomotic leakage was seen in PA patients with or without defunctioning stoma (6.2% vs. 7.0%, p = 0.680). Postoperative hospital stay was longer (7.0 vs. 6.0 days, p < 0.0001) and more often prolonged (19% vs. 13%, p = 0.03) in EO patients. Sixty-day mortality (2.9% vs. 6.4%, p < 0.0001), 90-day mortality (3.4% vs. 7.7%, p < 0.0001), and crude 3-year survival (81.2% vs. 58.7%, p < 0.0001) were significantly higher in EO patients, remaining significant after multivariable and PSM analysis.ConclusionThere are significant differences between elderly patients after left-sided CRC surgery with PA versus EO in terms of postoperative length of stay, short-term survival, 3-year overall survival, and relative survival at disadvantage of EO patients. This information could be important for decision making regarding surgical treatment in the elderly.

Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer: A Population-Based Study.

Location of the primary tumor has prognostic value and predicts the effect of certain therapeutics in synchronous metastatic colorectal cancer. We investigated whether the association between primary tumor resection (PTR) and overall survival (OS) also depends on tumor location. Data on synchronous metastatic colorectal cancer patients from the Netherlands Cancer Registry (n=16,106) and Surveillance, Epidemiology, and End Results (SEER) registry (n=19,584) were extracted. Cox models using time-varying covariates were implemented. Median OS for right-sided colon cancer (RCC), left-sided colon cancer, and rectal cancer was calculated using inverse probability weighting and a landmark point of 6 months after diagnosis as reference. The association between PTR and OS was dependent on tumor location (P<0.05), with a higher median OS of upfront PTR versus upfront systemic therapy in Netherlands Cancer Registry (NCR) of 1.9 (95% confidence interval: 0.9-2.8), 4.3 (3.3-5.6), and 3.4 (0.6-7.6) months in RCC, left-sided colon cancer and rectal cancer, respectively. In SEER data, the difference was 6.0 (4.0-8.0), 8.0 (5.0-10.0), and 10.0 (7.0-13.0) months, respectively. Hazard plots indicate a higher hazard of death 2 to 3 months after PTR in RCC. Upfront PTR is associated with improved survival regardless of primary tumor location. Patients with RCC appear to have less benefit because of higher mortality during 2 to 3 months after PTR.

Association between cigarette smoking and colorectal cancer sidedness: A multi-center big-data platform-based analysis

BackgroundSidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis.MethodsIn the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC.ResultsHistory of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 − 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC.ConclusionsHistory of smoking was associated with LSCRC in a positive dose–response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

Clinicopathological and Molecular Features of Patients with Early and Late Recurrence after Curative Surgery for Colorectal Cancer.

Simple SummaryColorectal cancer patients with early recurrence had advanced pathological node categories, pathological tumor, node, metastasis stages, adjuvant chemotherapy treatment, a worse overall survival rate, more liver metastases and more APC mutations than those with late recurrence. Patients with right-sided colon cancer tended to have early recurrence than those with left-sided colon cancer or rectal cancer. The postrecurrence survival rates were not significantly different between patients with early and late recurrence, which was observed in right-sided colon, left-sided colon and rectum. Multivariate analysis showed that old age, early recurrence, multiple-site recurrence and BRAF and NRAS mutations were independent prognostic factors.Background: Few reports have investigated genetic alterations between patients with early and late recurrence following curative surgery for colorectal cancer (CRC). Methods: A total of 1227 stage I–III CRC patients who underwent curative resection were included retrospectively. Among them, 236 patients had tumor recurrence: 139 had early (<2 years after surgery) and 97 had late (≥2 years after surgery) recurrence. Clinicopathological features and genetic alterations were compared between the two groups. Results: Compared to those with late recurrence, patients with early recurrence were more likely to have advanced pathological node (N) categories; tumor, node, metastasis (TNM) stages; adjuvant chemotherapy treatment; liver metastases; APC mutations; and worse five-year overall survival rates. Patients with right-sided colon cancer were more likely to develop early recurrence than were those with left-sided colon cancer or rectal cancer. Regarding rectal cancer, patients with early recurrence were more likely to be at advanced pathological N categories and TNM stages than those with late recurrence. Multivariate analysis revealed old age, early recurrence, multiple-site recurrence, and BRAF and NRAS mutations to be independent prognostic factors. Conclusion: CRC patients with early recurrence have a worse OS rate and more APC mutations than those with late recurrence.

Distinguishing Rectal Cancer from Colon Cancer Based on the Support Vector Machine Method and RNA-sequencing Data.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several studies have indicated that rectal cancer is significantly different from colon cancer in terms of treatment, prognosis, and metastasis. Recently, the differential mRNA expression of colon cancer and rectal cancer has received a great deal of attention. The current study aimed to identify significant differences between colon cancer and rectal cancer based on RNA sequencing (RNA-seq) data via support vector machines (SVM). Here, 393 CRC samples from the The Cancer Genome Atlas (TCGA) database were investigated, including 298 patients with colon cancer and 95 with rectal cancer. Following the random forest (RF) analysis of the mRNA expression data, 96 genes such as HOXB13, PRAC, and BCLAF1 were identified and utilized to build the SVM classification model with the Leave-One-Out Cross-validation (LOOCV) algorithm. In the training (n=196) and the validation cohorts (n=197), the accuracy (82.1 % and 82.2 %, respectively) and the AUC (0.87 and 0.91, respectively) indicated that the established optimal SVM classification model distinguished colon cancer from rectal cancer reasonably. However, additional experiments are required to validate the predicted gene expression levels and functions.

RNA-Associated Co-expression Network Identifies Novel Biomarkers for Digestive System Cancer.

Cancers of the digestive system are malignant diseases. Our study focused on colon cancer, esophageal cancer (ESCC), rectal cancer, gastric cancer (GC), and rectosigmoid junction cancer to identify possible biomarkers for these diseases. The transcriptome data were downloaded from the TCGA database (The Cancer Genome Atlas Program), and a network was constructed using the WGCNA algorithm. Two significant modules were found, and coexpression networks were constructed. CytoHubba was used to identify hub genes of the two networks. GO analysis suggested that the network genes were involved in metabolic processes, biological regulation, and membrane and protein binding. KEGG analysis indicated that the significant pathways were the calcium signaling pathway, fatty acid biosynthesis, and pathways in cancer and insulin resistance. Some of the most significant hub genes were hsa-let-7b-3p, hsa-miR-378a-5p, hsa-miR-26a-5p, hsa-miR-382-5p, and hsa-miR-29b-2-5p and SECISBP2 L, NCOA1, HERC1, HIPK3, and MBNL1, respectively. These genes were predicted to be associated with the tumor prognostic reference for this patient population.

Next-Generation Sequencing in Clinical Practice: Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

ObjectivesThis study aimed to compare the costs of a next-generation sequencing-based (NGS-based) panel testing strategy to those of a single-gene testing-based (SGT-based) strategy, considering different scenarios of clinical practice evolution.MethodsThree Italian hospitals were analysed, and four different testing pathways (paths 1, 2, 3, and 4) were identified: two for advanced non-small-cell lung cancer (aNSCLC) patients and two for unresectable metastatic colon-rectal cancer (mCRC) patients. For each path, we explored four scenarios considering the current clinical practice and its expected evolution. The 16 testing cases (4 scenarios × 4 paths) were then compared in terms of differential costs between the NGS-based and SGT-based approaches considering personnel, consumables, equipment, and overhead costs. Break-even and sensitivity analyses were performed. Data gathering, aimed at identifying the hospital setup, was performed through a semi-structured questionnaire administered to the professionals involved in testing activities.ResultsThe NGS-based strategy was found to be a cost-saving alternative to the SGT-based strategy in 15 of the 16 testing cases. The break-even threshold, the minimum number of patients required to make the NGS-based approach less costly than the SGT-based approach, varied across the testing cases depending on molecular alterations tested, techniques adopted, and specific costs. The analysis found the NGS-based approach to be less costly than the SGT-based approach in nine of the 16 testing cases at any volume of tests performed; in six cases, the NGS-based approach was found to be less costly above a threshold (and in one case, it was found to be always more expensive). Savings obtained using an NGS-based approach ranged from €30 to €1249 per patient; in the unique testing case where NGS was more costly, the additional cost per patient was €25.ConclusionsAn NGS-based approach may be less costly than an SGT-based approach; also, generated savings increase with the number of patients and different molecular alterations tested.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-020-00249-0.

Clinicopathological and Molecular Features of Colorectal Cancer Patients With Mucinous and Non-Mucinous Adenocarcinoma.

BackgroundThe prognosis of mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma (NMAC) in colorectal cancer (CRC) is controversial, and the molecular differences between them are unclear.MethodsBetween 2000 and 2010, a total of 1,483 CRC patients were included. Among them, 73 patients (4.9%) were diagnosed with MAC. The clinicopathological features and genetic alterations were compared between MAC and NMAC.ResultsAfter propensity score matching to balance age and sex between MAC and NMAC patients, 292 CRC patients (73 MAC and 219 NMAC) were enrolled in the analysis at a 1:3 ratio. In right-sided colon cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, and advanced T category and tumor, node, metastasis (TNM) stage, chemotherapy, and a similar 5-year overall survival (OS) rate compared with patients with NMAC. In left-sided colon cancer and rectal cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, lymphovascular invasion, advanced T and N categories and TNM stages, chemotherapy, and a worse 5-year OS rate than patients with NMAC. Regarding genetic alterations, for NMAC, right-sided colon cancer had more BRAF mutations than left-sided colon cancer and rectal cancer. For MAC, right-sided colon cancer was associated with more microsatellite instability-high tumors and more AKT1 mutations than left-sided colon cancer and rectal cancer.ConclusionThe genetic alterations are distinct between MAC and NMAC in CRC. Tumor location may have an impact on genetic alterations and patient prognosis in MAC and NMAC.

Differential Expression of miR-20a and miR-145 in Colorectal Tumors as Potential Location-specific miRNAs.

MicroRNAs (miRNAs), as tissue specific regulators of gene transcription, may be served as biomarkers for Colorectal Cancer (CRC). This study aimed to investigate the potential role of the cancer-related hsa-miRNAs as biomarkers in Colon Cancer (CC) and Rectal Cancer (RC). A total of 148 CRC samples (74 rectum and 74 colon) and 74 adjacent normal tissues were collected to examine the differential expression of selected ten hsa-miRNAs using quantitative Reverse Transcriptase PCR (qRT-PCR). The significantly elevated levels of miR-21, miR-133b, miR-18a, miR-20a, and miR-135b, and decreased levels of miR-34a, miR-200c, miR-145, and let-7g were detected in colorectal tumors compared to the healthy tissues (P<0.05). Hsa-miR-20a was significantly overexpressed in rectum compared to colon (p =0.028) from a cut-off value of 3.15 with a sensitivity of 66% and a specificity of 60% and an AUC value of 0.962. Also, hsa-miR-145 was significantly overexpressed in colon compared to the rectum (p =0.02) from a cut-off value of 3.9 with a sensitivity of 55% and a specificity of 61% and an AUC value of 0.91. In conclusion, hsa-miR-20a and hsa-miR-145, as potential tissue-specific biomarkers for distinguishing RC and CC, improve realizing the molecular differences between these local tumors.