Left-sided Colon Cancer Patients Research Articles

Differences of RAS/BRAF mutations between ISCC and RSCC in a Chinese population.

e15636 Background: According to the location and different clinical manifestations, colon cancer can be divided into left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC). There are significant differences in morphology, molecular biology, and drug sensitivity between these two type. In addition, colorectal cancer is associated with the mutation of many essential tumor suppressor genes, such as proto-oncogene (KRAS), serine/threonine protein kinase (BRAF), etc. At that point, this study retrospectively analyzed the RAS/BRAF mutation landscape and studied the gene expression differences between RAS/BRAF-mutant and wild-type patients respectively in LSCC and RSCC, to provide some reference for potential treatment plans. Methods: We retrospectively profiled the somatic mutations of 497 patients with colon cancer from the General Hospital of Southern Theatre Command and the TCGA database using 808-gene-panel target-capture next-generation sequencing. Tumor mutation burdens (TMB) were calculated using an Acornmed panel with 808 cancer-related genes. Results: Among 415 LSCC, 48.7% (n = 202) patients harbored RAS mutations, of which 183 carried KRAS mutations and 19 had NRAS mutations. Five main subtypes of KRAS mutation were detected including G12D (28.7%), G12V (17.5%), G13D (13.2%), A146T(8.5%), G12C (7.9%). 3% (11) of LSCC patients were found to have BRAF mutation, including BRAF V600E(63.6%), D594G(18.2%), G466E(9.1%), K601E(9.1%). We explored differentially expressed genes between RAS/BRAF-mutant and wild-type patients. The top5 mutant genes found only in LSCC RAS/BRAF-mutant cohort include JAK2(3%), TERT(2%), MSH6(2%), KMT2A(1%), NOTCH1(1%). In contrast, genes found only in LSCC patients with RAS/BRAF wild type include LATS2(2%), SMARCA4(2%), CBL(1%), SLX4(1%), CDKN2A(1%). Among 82 RSCC, 50% (41) patients harbored RAS mutations, of which 39 carried KRAS mutations and 2 carried NRAS mutations. 9% (39) of RSCC patients were found BRAF mutation, and the BRAF V600E was the only subtype found in the RSCC. In terms of differentially expressed genes, the top5 mutant genes found only in RAS/BRAF-mutant RSCC include NSD1(6%), ASXL2(4%), BARD1(4%), PPP2R1A(4%), SPRED1(4%), while genes found only in RAS/BRAF wild-type RSCC include ERBB2(17.6%), DICER1(11.8%), EP300(11.8%), ARID2(9%), BRIP1(9%).The TMB of RAS/BRAF wild-type RSCC patients was 33.2 mut/Mb, significantly higher than that of RAS/BRAF wild-type LSCC patients (7.0 mut/Mb, P = 0.01). Conclusions: RAS mutation and subtype were almost the same in LSCC and RSCC cohorts. BRAF mutation mainly occurred in RSCC, and the mutation subtype in RSCC was found only V600E, but we found three other BRAF subtypes D594G, G466E, and K601E in the LSCC cohort. Considering the differential expression genes in RAS/BRAF-mutant and wild-type cohorts in RSCC and LSCC patients, there may be more options for genetic targets in the future for LSCC and RSCC treatment.

New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Development and validation of a new stage-specific nomogram model for predicting cancer-specific survival in patients in different stages of colon cancer: A SEER population-based study and external validation.

The effects of laterality of the primary tumor on survival in patients in different stages of colon cancer are contradictory. We still lack a strictly evaluated and validated survival prediction tool, considering the different roles of tumor laterality in different stages. A total of 101,277 and 809 colon cancer cases were reviewed using the Surveillance, Epidemiology, and End Results database and the First Affiliated Hospital of Xi 'an Jiaotong University database, respectively. We established training sets, internal validation sets and external validation sets. We developed and evaluated stage-specific prediction models and unified prediction models to predict cancer-specific survival and compared the prediction abilities of these models. Compared with right-sided colon cancers, the risk of cancer-specific death of left-sided colon cancer patients was significantly higher in stage I/II but was markedly lower in stage III patients. We established stage-specific prediction models for stage I/II and stage III separately and established a unified prediction model for all stages. By evaluating and validating the validation sets, we reported high prediction ability and generalizability of the models. Furthermore, the stage-specific prediction models had better predictive power and efficiency than the unified model. Right-sided colon cancer patients have better cancer-specific survival than left-sided colon cancer patients in stage I/II and worse cancer-specific survival in stage III. Using stage-specific prediction models can further improve the prediction of cancer-specific survival in colon cancer patients and guide clinical decisions.

The impact of inflammatory markers on prognosis of stage II colon cancers depends on tumour sidedness.

Accumulating evidence has reported a high correlation between inflammatory markers and oncological outcomes in colorectal cancer. In the present study, we aimed to assess the prognostic values of five inflammatory markers in stage II colon cancer patients with different tumour locations. The consecutive stage II colon adenocarcinoma patients undergoing curative resection were analysed retrospectively. ROC curves and the area under the curve (AUCs) via bootstrap method were used to analyse the prognostic impact of various inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and prognostic nutrition index (PNI). A total of 768 patients were enrolled for analysis. In univariate analysis, right-sided colon cancer (RCC) patients have significantly higher mean levels of all inflammatory markers than left-sided colon cancer (LCC) patients. In multivariate analyses, high NLR in LCC (P= 0.025) and low PNI in both RCC (P= 0.049) and LCC (P= 0.027) were significantly associated with a worse OS while none of the inflammatory markers was found to have a significant impact on DFS or CSS. The profiles and prognostic impact of inflammatory markers are significantly different between stage II RCC and LCC patients. Researchers should take sidedness into consideration when addressing survival analysis of inflammatory markers.

Tumour genotypes account for survival differences in right- and left-sided colon cancers.

We sought to identify genetic differences between right- and left-sided colon cancers and using these differences explain lower survival in right-sided cancers. A retrospective review of patients diagnosed with colon cancer was performed using The Cancer Genome Atlas, a cancer genetics registry with patient and tumour data from 20 North American institutions. The primary outcome was 5-year overall survival. Predictors for survival were identified using directed acyclic graphs and Cox proportional hazards models. A total of 206 right- and 214left-sided colon cancer patients with 84 recorded deaths were identified. The frequency of mutated alleles differed significantly in 12 of 25genes between right- and left-sided tumours. Right-sided tumours had worse survival with a hazard ratio of 1.71 (95% confidence interval 1.10-2.64, P=0.017). The total effect of the genetic loci on survival showed five genes had a sizeable effect on survival: DNAH5, MUC16, NEB, SMAD4, and USH2A. Lasso-penalized Cox regression selected 13 variables for the highest-performing model, which included cancer stage, positive resection margin, and mutated alleles at nine genes: MUC16, USH2A, SMAD4, SYNE1, FLG, NEB, TTN, OBSCN, and DNAH5. Post-selection inference demonstrated that mutations in MUC16 (P=0.01) and DNAH5 (P=0.02) were particularly predictive of 5-year overall survival. Our study showed that genetic mutations may explain survival differences between tumour sites. Further studies on larger patient populations may identify other genes, which could form the foundation for more precise prognostication and treatment decisions beyond current rudimentary TNM staging.

Comparison of Resected Malignant Tumors of the Right- and Left-Sided Colon—Is There a Difference?

Embryological, anatomical, and immunological differences between the right-sided and left-sided colons are well known, but the difference in oncological behavior of colon tumors has only recently become the main subject of studies. Published articles propose that there is a difference not only in symptoms, but also in survival. Our aim was to analyze the clinicopathological and oncological differences among our patients who had been operated for colon cancer in our department. We examined the historical data of our patients who underwent colon resection for malignancy between 1st of January 2016 and 31st of December 2018. Tumor markers, histological results, postoperative complications, and oncological therapies were investigated. The primary outcome was overall survival. We analyzed our patients’ survival data with Kaplan–Meier log-rank test and Cox regression analysis. In our study, 267 patients were enrolled. One hundred thirty-three (49.8%) patients had right-sided colon cancer; 134 (50.2%) patients had left-sided colon cancer. Patients with right-sided colon cancer were significantly more likely to have mucinous adenocarcinoma (p = 0.037). No significant differences were revealed in overall survival between right-sided colon cancer and left-sided colon cancer patients (p = 0.381). Additional subgroup analysis showed that there were no significant differences in overall survival for laterality neither in the metastatic group (p = 0.824) nor in the non-metastatic group (p = 0.345). Based on the conflicting previous study results, our findings repeatedly highlight that the relationship between tumor location in the colon and overall survival is not straightforward.

The establishment of a hub differential gene model to predict prognosis in stage II and III right- and left-sided colon cancer patients.

BackgroundIt is now recognized that the symptoms of colon cancer differ according to whether the tumor is located on the left or right side of the patient. The results of the present study point to the differences in the tissue and embryonic origins of left- and right-sided colon cancer that cause the variations in molecular typing. The research purpose of this study is to establish a core differential gene scoring model and proved its effect.MethodsWe downloaded transcriptome data and clinical information from The Cancer Genome Atlas (TCGA). A total of 243 patients in stages II and III were grouped according to the colon cancer site. Then we screened for differential transcriptome products. The corresponding differential gene were performing a corresponding protein interaction analysis. We used 12 algorithms in Cytoscape to calculate the hub genes and a total of 37 hub genes were obtained finally. We extracted the first principal component value (PC1) of the hub genes to evaluate the effectiveness of screening. Cox regression analysis was performed for the differential genes. Finally, we performed a prognostic analysis on right-sided colon cancer patients using the BST2 gene, PC1 and relevant clinical information.ResultsAfter screening for differentially expressed genes, 37 hub genes were obtained with appropriate algorithms. PC1 showed differences in hub genes between left- and right-sided colon cancer patients. BST2 and 31 other genes were identified as significant by Cox regression analysis and were significantly mutated in patients with right-sided colon cancer. Finally, we selected the BST2 gene and relevant clinical information as the prognostic factors to build a scoring model. The prediction effect of the model was satisfied.ConclusionsWe constructed a prognostic model based on BST2, PC1, and other relevant clinical information and proved its good effect.

The Long-Term Recurrence Rate and Survival of Obstructive Left-Sided Colon Cancer Patients: A Stent as A Bridge to Surgery Versus Emergency Surgery

The Long-Term Recurrence Rate and Survival of Obstructive Left-Sided Colon Cancer Patients: A Stent as A Bridge to Surgery Versus Emergency Surgery

Discovering the molecular differences between right- and left-sided colon cancer using machine learning methods

BackgroundIn recent years, the differences between left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have received increasing attention due to the clinicopathological variation between them. However, some of these differences have remained unclear and conflicting results have been reported.MethodsFrom The Cancer Genome Atlas (TCGA), we obtained RNA sequencing data and gene mutation data on 323 and 283 colon cancer patients, respectively. Differential analysis was firstly done on gene expression data and mutation data between LCC and RCC, separately. Machine learning (ML) methods were then used to select key genes or mutations as features to construct models to classify LCC and RCC patients. Finally, we conducted correlation analysis to identify the correlations between differentially expressed genes (DEGs) and mutations using logistic regression (LR) models.ResultsWe found distinct gene mutation and expression patterns between LCC and RCC patients and further selected the 30 most important mutations and 17 most important gene expression features using ML methods. The classification models created using these features classified LCC and RCC patients with high accuracy (areas under the curve (AUC) of 0.8 and 0.96 for mutation and gene expression data, respectively). The expression of PRAC1 and BRAF V600E mutation (rs113488022) were the most important feature for each model. Correlations of mutations and gene expression data were also identified using LR models. Among them, rs113488022 was found to have significance relevance to the expression of four genes, and thus should be focused on in further study.ConclusionsOn the basis of ML methods, we found some key molecular differences between LCC and RCC, which could differentiate these two groups of patients with high accuracy. These differences might be key factors behind the variation in clinical features between LCC and RCC and thus help to improve treatment, such as determining the appropriate therapy for patients.

The incidence and risk factors of sessile serrated adenomas in left side colon cancer patients after curative surgery

Sessile serrated adenomas (SSAs) are precursors of colorectal cancer (CRC). However, there are limited data on detection rates of this premalignant lesion during colonoscopy surveillance in patients with a history of left side colonic resection for cancer. We aimed to identify the incidence and risk factors of SSAs in post-left side colectomy patients.We retrospectively reviewed the medical records of patients who had undergone left side colectomy for colon and rectal cancer between September 2009 and September 2016 and had at least 1 follow-up colonoscopy. Patient baseline characteristics, SSA diagnoses and characteristics, and colonoscopy information were collected.In total, 539 patients were enrolled. At the first follow-up (mean duration 11.5 months), 98 SSAs were identified (22.2%). At the second follow-up (mean duration 25.8 months), 51 SSAs were identified in 212 patients (24.0%). Multivariate analysis showed that alcohol intake (hazard ratio [HR] 1.524; 95% confidence interval [CI] .963–2.411, P = .041), excellent bowel preparation (HR 2.081; 95% CI 1.214–3.567, P = .049), and use of a transparent cap (HR 1.702; 95% CI 1.060–2.735, P = .013) were associated with higher SSA incidence in the first surveillance colonoscopy, while body mass index (BMI) ≥ 25.0 (HR 1.602; 95% CI 1.060–2.836) was associated with a significantly increased risk of SSAs in the second surveillance.Considering the endoscopic appearance of SSAs, adequate bowel preparation and use of transparent caps during postoperative surveillance colonoscopy can increase the diagnosis rate. Modification of alcohol intake and BMI may reduce the incidence of SSAs in left side colon cancer patients.

Temporal Trends of Sex Disparity in Incidence and Survival of Colorectal Cancer: Variations by Anatomical Site and Age at Diagnosis.

PurposeThe incidence of colorectal cancer (CRC) varies by age, sex, and anatomical subsite. Few studies have examined the temporal trends of age-specific sex disparity in incidence and survival by age at diagnosis and anatomical site.Patients and MethodsThe study was performed on all incident cases of CRC, using data derived from the nationwide Swedish Cancer Register between 1960 and 2014, including right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer. Male-to-female age-standardized incidence rate ratio (IRR) and male-to-female five-year survival rate ratio (SRR) were calculated as the main indicators. Furthermore, we performed joinpoint regression analyses to estimate average annual percentage change.ResultsThe overall male-to-female IRR was 1.05 for RCC, 1.31 for LCC, and 1.66 for rectal cancer. Male-to-female IRR increased steadily for RCC by an average of 0.4% per year until the mid-1990s and then decreased gradually by an average of 1.0% per year. LCC patients showed an increase of 0.6% per year since the mid-1970s. For rectal cancer, a non-significant random fluctuation was noted during the study period. The temporal trends of male-to-female IRR varied by age at diagnosis. The male-to-female SRR was 0.87 for RCC, 0.88 for LCC, and 0.86 for rectal cancer, which remained relatively stable during the study period.ConclusionSex disparity of CRC is age-, period-, and anatomical subsite-dependent. Further studies are needed to investigate the underlying contributing factors.

Tumor sidedness influences prognostic impact of lymph node metastasis in colon cancer patients undergoing curative surgery

This study aimed to evaluate prognostic impacts of the number of lymph nodes (LNs) examined and LN ratio on cancer-specific mortality after surgery in patients with right-sided colon cancer (RCC) or left-sided colon cancer (LCC) using the Surveillance, Epidemiology, and End Results database. Number of LNs examined and LN ratio were treated as categorical and/or continuous. Competing risks proportional hazards regressions adjusted by propensity score were performed. All included patients had stage I, II, or III disease, and 45.1% of them had RCC. RCC and LCC patients with high level of LNs examined had better prognosis after segmental resection or hemicolectomy. RCC and LCC patients with higher LN ratio had worse prognosis regardless of surgery. Survival benefit of having high level of LNs examined was observed in RCC patients with stage I, II, or III disease, but only in LCC patients with stage II disease. Both higher LN ratio and high level of LN were negative prognostic factors for cancer-specific mortality in stage III patients regardless of tumor sidedness. In conclusion, RCC patients in various conditions had worse or comparable prognosis compared to their LCC counterparts, which reflected the severity of LN metastasis.

Joint effect of pre-operative anemia and perioperative blood transfusion on outcomes of colon-cancer patients undergoing colectomy.

BackgroundBoth pre-operative anemia and perioperative (intra- and/or post-operative) blood transfusion have been reported to increase post-operative complications in patients with colon cancer undergoing colectomy. However, their joint effect has not been investigated. The purpose of this study was to evaluate the joint effect of pre-operative anemia and perioperative blood transfusion on the post-operative outcome of colon-cancer patients after colectomy.MethodsWe identified patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database 2006–2016 who underwent colectomy for colon cancer. Multivariate logistic regression analysis was employed to assess the independent and joint effects of anemia and blood transfusion on patient outcomes.ResultsA total of 35,863 patients—18,936 (52.8%) with left-side colon cancer (LCC) and 16,927 (47.2%) with right-side colon cancer (RCC)—were identified. RCC patients were more likely to have mild anemia (62.7%) and severe anemia (2.9%) than LCC patients (40.2% mild anemia and 1.4% severe anemia). A total of 2,661 (7.4%) of all patients (1,079 [5.7%] with LCC and 1,582 [9.3%] with RCC) received a perioperative blood transfusion. Overall, the occurrence rates of complications were comparable between LCC and RCC patients (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.95–1.07; P = 0.750). There were significant joint effects of anemia and transfusion on complications and the 30-day death rate (P for interaction: 0.010). Patients without anemia who received a transfusion had a higher risk of any complications (LCC, OR = 3.51; 95% CI = 2.55–4.85; P < 0.001; RCC, OR = 3.74; 95% CI = 2.50–5.59; P < 0.001), minor complications (LCC, OR = 2.54; 95% CI = 1.63–3.97; P < 0.001; RCC, OR = 2.27; 95% CI = 1.24–4.15; P = 0.008), and major complications (LCC, OR = 5.31; 95% CI = 3.68–7.64; P < 0.001; RCC, OR = 5.64; 95% CI = 3.61–8.79; P < 0.001), and had an increased 30-day death rate (LCC, OR = 6.97; 95% CI = 3.07–15.80; P < 0.001; RCC, OR = 4.91; 95% CI = 1.88–12.85; P = 0.001) than patients without anemia who did not receive a transfusion.ConclusionsPre-operative anemia and perioperative transfusion are associated with an increased risk of post-operative complications and increased death rate in colon-cancer patients undergoing colectomy.

Circulating Tumor Cells in Right- and Left-Sided Colorectal Cancer.

Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells (CTC) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- (LCC) compared to right-sided (RCC) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.

Impact of primary colorectal Cancer location on the KRAS status and its prognostic value

BackgroundColorectal cancer (CRC) originating from the right-sided or left-sided colon is distinct clinicopathological entity. The KRAS status and its prognostic value in CRC remain controversial. This study aimed to investigate the association of KRAS status with clinicopathological features and prognostic value in CRC.Methods178 colon cancer and 145 rectal cancer patients were enrolled. KRAS mutation test was performed on paraffin-embedded tumor samples using PCR methods. The colon cancer was divided into right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Studies that reported the association of KRAS mutation with CRC clinical features and prognosis in databases were searched prior to 2018. The data of the present study was combined with the data of published studies using meta-analysis methods.ResultsNo significant difference between colon cancer and rectal cancer regarding the KRAS status. The KRAS mutation was much frequent in RCC than in LCC (p = 0.010). 17 studies with 11,385 colon cancer patients were selected, the pooled results of our data and previous published data showed that KRAS mutation was more frequent in RCC compared with in LCC (p < 0.01); KRAS mutation was not associated with the prognosis in RCC patient; however, KRAS mutation indicated a poor prognosis in LCC patients compared with KRAS wild type (p < 0.01).ConclusionKRAS status has no difference between colon cancer and rectal cancer. KRAS mutation was more frequent in RCC than in LCC, and associated with a poor prognosis in LCC patients, but not in RCC patients.

Does the Different Locations of Colon Cancer Affect the Oncologic Outcome? A Propensity-Score Matched Analysis.

PurposeWe evaluate the prognostic value of primary tumor location for oncologic outcomes in patients with colon cancer (CC).MethodsCC patients treated with curative surgery between 2009 and 2012 were classified into 2 groups: right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Recurrence-free survival (RFS) and overall survival (OS) were examined based on tumor stage. Propensity scores were created using eight variables (age, sex, T stage, N stage, histologic grade, presence of lymphovascular invasion/perineural invasion, and microsatellite instability status).ResultsOverall, 2,329 patients were identified. The 5-year RFSs for RCC and LCC patients were 89.7% and 88.4% (P = 0.328), respectively, and their 5-year OSs were 90.9% and 93.4% (P = 0.062). Multivariate survival analyses were carried out by using the Cox regression proportional hazard model. In the unadjusted analysis, a marginal increase in overall mortality was seen in RCC patients (hazard ratio [HR], 1.297; 95% confidence interval [CI], 0.987–1.704, P = 0.062); however, after multivariable adjustment, similar OSs were observed in those patients (HR, 1.219; 95% CI, 0.91–1.633; P = 0.183). After propensity-score matching with a total of 1,560 patients, no significant difference was identified (P = 0.183). A slightly worse OS was seen for stage III RCC patients (HR, 1.561; 95% CI, 0.967–2.522; P = 0.068) than for stage III LCC patients. The 5-year OSs for patients with stage III RCC and stage III LCC were 85.5% and 90.5%, respectively (P = 0.133).ConclusionAlthough the results are inconclusive, tumor location tended to be associated with OS in CC patients with lymph node metastasis, but it was not related to oncologic outcome.

Plasma metabolomic profiling distinguishes right-sided from left-sided colon cancer

BackgroundMany studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. MethodsIn this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis. ResultsMetabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5′-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC. ConclusionsIdentified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.

Correlation between K-ras gene mutation and clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites

Objective To analyze the correlation between K-ras gene mutation and clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites. Methods The clinical and pathological records of 69 patients who were pathologically confirmed as colorectal cancer and tested K-ras gene status at Wuxi People's Hospital Affiliated to Nanjing Medical University between May 2007 and August 2017 were adopted. The correlation between clinicopathological characteristics and prognosis of colorectal cancer patients with different primary sites and K-ras gene mutation status were retrospectively analyzed. And the patients were visited to adopt the prognosis data and perform the Kaplan-Meier survival analysis. Results The K-ras mutation rate was 50.7% (35/69), including 40.0% (12/30) in left-side colon cancer, 73.3% (11/15) in right-side colon cancer and 50.0% (12/24) in rectal cancer. The mutation rate of K-ras gene in patients ≥ 60 years old [61.5% (24/39) vs. 36.7% (11/30), χ2 = 4.197, P = 0.041] or serum CA19-9 raising up abnormally was conspicuously high [65.6% (19/29) vs. 37.5% (15/40), χ2 = 5.486, P = 0.019]. Other clinicopathological characteristics, such as gender, lesion location, histological classification, TNM stage, serum CEA expression, clinical features had no correlation with K-ras gene mutation status (all P > 0.05). And no relationship was found between prognosis and overall survival of colorectal cancer patients with different primary sites and K-ras gene mutation status (χ2 = 0.001, P = 0.997; χ2 = 0.583, P = 0.445). In general, the 5-year survival rate of left-side colon cancer patients was highest (76.9%), followed by rectal cancer (69.7%), and right-side colon cancer was lowest (31.3%). The primary site of colorectal cancer was related to the overall survival of patients (χ2 = 11.004, P = 0.004). Conclusions K-ras gene mutation in colorectal cancer is closely related to age and serum CA19-9 levels of the patients. The prognosis of left-side colon cancer is best, rectal cancer second, and right-side colon cancer poorest. Whether K-ras gene mutation is the prognostic factor of colorectal cancer is not clear. Testing the K-ras gene status and serum tumor index expression, distinguish the primary site and age group will provide the theory basis and promote the clinical targeted therapy and improve the survival of colorectal cancer patients. Key words: Intestinal neoplasms; Genes, ras; Pathology, clinical; Prognosis

Clinicopathological differences and survival outcomes with first-line therapy in patients with left-sided colon cancer and rectal cancer: Pooled analysis of 2879 patients from AGITG (MAX), COIN, FOCUS2, OPUS, CRYSTAL and COIN-B trials in the ARCAD database

PurposePatients with left-sided colon tumours have better survival and respond differently to biologics compared with patients with right-sided tumours. Left-sided colon tumours and rectal cancers are often grouped together. Herein, we examined the clinicopathological differences and outcomes between left-sided colon and rectal cancers. Patients and methodsData from 2879 metastatic colorectal cancer patients enrolled on six first-line clinical trials during 2004–2010 were pooled. Patients were included if the primary tumour origin was clearly defined. Progression-free survival (PFS) and overall survival (OS) were compared in the two groups after adjusting for patient and tumour characteristics, metastatic sites and the first-line regimen. ResultsIn total, 1374 patients with metastatic left-sided colon cancer and 1505 patients with metastatic rectal cancers were evaluated. Left-sided colon cancer patients were more likely to be female (40.1% versus 32.6%; P < 0.0001) and older (31.0% ≥ 70 years versus 25.8%; P = 0.0033) compared with rectal cancers patients. Patients with left-sided colon cancer had higher rates of liver metastases (80.9% versus 72.3%, P < 0.0001) but lower rates of lung metastases (34.2% versus 53.8%, P < 0.0001). KRAS mutations were slightly less frequent among left-sided tumours (34.8% versus 40.5%; P = 0.0103). Patients with left-sided tumours had approximately similar PFS (median 7.4 versus 6.9 months; hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.87–1.03; P = 0.1998) and OS (median 17.4 versus 16.6 months; HR 0.99, 95% CI 0.91–1.07; P = 0.7597) compared with rectal cancer patients. ConclusionThe site of tumour origin within the left side was not prognostic of outcomes. Moreover, neither bevacizumab nor cetuximab impacted, differently, the findings of the comparisons in outcomes between patients with left-sided colon tumours or rectal cancers.

Different Anatomical Subsites of Colon Cancer and Mortality: A Population-Based Study.

Background In terms of incidence and pathogenesis, right-sided colon cancer (RCC) and left-sided colon cancer (LCC) exhibit several differences. However, whether existing differences could reflect the different survival outcomes remains unclear. Therefore, we aimed to ascertain the role of location in the prognosis. Methods We identified colon cancer cases from the Surveillance, Epidemiology, and End Results database between 1973 and 2012. Differences among subsites of colon cancer regarding clinical features and metastatic patterns were compared. The Kaplan-Meier curves were conducted to compare overall and disease-specific survival in relation to cancer location. The effect of tumour location on overall and cancer-specific survival was analysed by Cox proportional hazards model. Results A total of 377,849 patients from SEER database were included in the current study, with 180,889 (47.9%) RCC and 196,960 (52.1%) LCC. LCC was more likely to metastasize to the liver and lung. Kaplan-Meier curves demonstrated that LCC patients had better overall and cancer-specific survival outcomes. Among Cox multivariate analyses, LCC was associated with a slightly reduced risk of overall survival (HR, 0.92; 95% CI, 0.92-0.93) and cancer-specific survival (HR, 0.92; 95% CI, 0.91-0.93), even after adjusted for other variables. However, the relationship between location and prognosis was varied by subgroups defined by age, year at diagnosis, stage, and therapies. Conclusions We demonstrated that LCC was associated with better prognosis, especially for patients with distant metastasis. Future trails should seek to identify the underlying mechanism.