Advanced Colon Cancer Patients Research Articles

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy in patients with pathological T3-4 locally advanced colon cancer

The safety and effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in pathological T3-4 locally advanced (pT3N+M0 and pT4NxM0) colon cancer (CC) patients with radical resection need further study. Clinical and pathological information of pT3-4 locally advanced CC patients who received radical surgery in our hospital from January 2018 to December 2020 were analyzed. The prognosis of patients was estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Among 927 patients, 10.4% (96/927) received prophylactic HIPEC based on 5-FU, 4.6% (43/927) received prophylactic HIPEC based on lobaplatin, 85.0% (788/927) received conventional therapy. The incidence of metachronous peritoneal carcinomatosis (mPC) was 9.4%. Complications occurred in 32 patients (4.1%) in the conventional therapy group, 6 patients (6.3%) in the prophylactic HIPEC group based on 5-FU and 3 patients (7.0%) in the prophylactic HIPEC group based on lobaplatin within 30 days after surgery (5-FU vs. conventional therapy group, p=0.464; Lobaplatin vs. conventional therapy group, p=0.591). Multivariate Cox regression analysis revealed that prophylactic HIPEC based on either 5-FU or lobaplatin regimen could not effectively improve mPC-free survival (5-FU: p=0.020, HR=1.927, 95% CI, 1.111-3.343; Lobaplatin: p=0.167, HR=0.247, 95% CI, 0.034-1.796), overall survival (5-FU: p=0.361, HR=1.360, 95% CI, 0.703-2.634; Lobaplatin: p=0.780, HR=0.816, 95% CI, 0.195-3.416) and disease-free survival (5-FU: p=0.525, HR=1.149, 95% CI, 0.749-1.760; Lobaplatin: p=0.117, HR=0.488, 95% CI, 0.199-1.198). Early prophylactic HIPEC based on 5-FU or lobaplatin subsequent to radical resection for patients with pT3-4 locally advanced CC is safe, but not effective in reducing the risk for mPC.

Can the Inflammatory Cell Ratio NLR and PLR be Used as a Reliable Marker in Colon Cancer? A Prospective Study.

Simple approaches for detecting the tumor stage of colon cancer patients are required during the preoperative period. In recent years, the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been employed as predictive parameters for systemic inflammatory response and long-term prognosis in a variety of malignancies. The purpose of this study was to determine whether the NLR and PLR correspond with tumor characteristics in colon cancer patients. About 90 patients with colon cancer who reported to our institute during the time interval July 2021 to December 2022 were included in the study. The NLR and PLR were calculated using data obtained from a complete blood count evaluation. The relationship between inflammatory cell ratio and tumor-specific characteristics were analyzed. Neutrophil-lymphocyte ratio and PLR correlated with pTNM staging in 88 patients. Two patients exhibited diffuse peritoneal metastasis. A significant association was found between PLR and early (Tis + T1 + T2) and advanced (T3 + T4) groups. Although the difference was not statistically significant, patients with lymphovascular invasion (LVI) and perineural invasion (PNI) had greater mean NLR and PLR. Platelet-lymphocyte ratio was found to be more accurate than NLR in predicting colon cancer tumor depth/invasion. A high PLR value aids in prognosticating advanced T-stage colon cancer patients and can be used as a valuable tool for preoperative counseling, but it must be validated with a survival analysis. The tumor microenvironment contains a variety of inflammatory cells that contribute to the growth and spread of the neoplasm. The NLR and PLR have been shown to be clinically and prognostically important in a variety of gastrointestinal cancers. The results of this study demonstrate that PLR was more accurate than NLR in predicting colon cancer tumor depth/invasion. Also, a high PLR value aids in prognosticating advanced T-stage colon cancer patients and may be used as a valuable tool for preoperative counseling. Ramesh SK, Swain SK, Munikrishnan V, et al. Can the Inflammatory Cell Ratio NLR and PLR be Used as a Reliable Marker in Colon Cancer? A Prospective Study. Euroasian J Hepato-Gastroenterol 2023;13(2):61-65.

Real-life experiences and barriers to adjuvant chemotherapy in Saudi patients with advanced stage II and stage III colon cancer.

Colorectal cancer is the most common malignancy in Saudi males and third most common in females. Patients with locally advanced colon cancer may eventually develop metastatic disease if not treated promptly and according to guidelines. The recent National Comprehensive Cancer Network guideline recommends tumor resection followed by adjuvant chemotherapy for stage III and high-risk stage II tumors. Therefore, the objective of this study was to characterize patients with locally advanced colon cancer and identify factors associated with the use of adjuvant chemotherapy and the addition of oxaliplatin in locally advanced colon cancer patients. All patients diagnosed with locally advanced colon cancer at National Guard Health Affairs (NGHA) during 2016-2021 were investigated. Patients' characteristics were compared using Chi-square and Fisher exact test, whereas predictors of adjuvant chemotherapy/Oxaliplatin use were identified using univariate and multivariate logistic regression. Out of 222 patients diagnosed with locally advanced colon cancer, 133 received adjuvant chemotherapy. Factors associated with adjuvant chemotherapy administration were age and smoking status. In the multivariable analysis, older patients were less likely to receive oxaliplatin than younger patients. Stage III patients diagnosed during 2019-2021 had 5.61 times higher odds of receiving oxaliplatin. The findings of this study show that older patients and smokers are less likely to be treated with adjuvant chemotherapy. Moreover, age as well as diagnosis year were important determinants of oxaliplatin administration in stage III locally advanced colon cancer patients.

Whole-course care in photodynamic therapy of colorectal cancer: A short communication

Photodynamic therapy is now widely used in different oncologic fields. It is feasible for the treatment of early, non-surgical and non-obstructive cancers. Also, in gastroenterology, where it was a few attempts to treat both the premalignant lesion and advanced colorectal cancer. Photodynamic therapy provides a new treatment option for advanced colon cancer patients with severe obstruction and elderly patients whose cardiopulmonary function cannot tolerate surgery, and effective nursing support throughout the treatment is the key to ensure successful treatment. This study reported the effect of whole-course care for colorectal cancer patients undergoing photodynamic therapy in the Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.

Hypoxia induced deregulation of sphingolipids in colon cancer is a prognostic marker for patient outcome

Sphingolipids are important for the physicochemical properties of cellular membranes and deregulated in tumors. In human colon cancer tissue ceramide synthase (CerS) 4 and CerS5 are reduced which correlates with a reduced survival probability of late-stage colon cancer patients. Both enzymes are reduced after hypoxia in advanced colorectal cancer (CRC) cells (HCT-116, SW620) but not in non-metastatic CRC cells (SW480, Caco-2). Downregulation of CerS4 or CerS5 in advanced CRC cells enhanced tumor formation in nude mice and organoid growth in vitro. This was accompanied by an enhanced proliferation rate and metabolic changes leading to a shift towards the Warburg effect. In contrast, CerS4 or CerS5 depletion in Caco-2 cells reduced tumor growth in vivo. Lipidomic and proteomic analysis of membrane fractions revealed significant changes in tumor-promoting cellular pathways and cellular transporters. This study identifies CerS4 and CerS5 as prognostic markers for advanced colon cancer patients and provides a comprehensive overview about the associated cellular metabolic changes. We propose that the expression level of CerS4 and CerS5 in colon tumors could serve as a basis for decision-making for personalized treatment of advanced colon cancer patients.Trial registration: The study was accredited by the study board of the Deutsche Krebsgesellschaft (Registration No: St-D203, 2017/06/30, retrospectively registered).

A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer.

Colon cancer (CC), one of the most common malignancies worldwide, lacks an effective prognostic prediction biomarker. N7-methylguanosine (m7G) methylation is a common RNA modification type and has been proven to influence tumorigenesis. However, the correlation between m7G-related genes and CC remains unclear. The gene expression levels and clinical information of CC patients were downloaded from public databases. Twenty-nine m7G-related genes were obtained from the published literature. Via unsupervised clustering based on the expression levels of m7G-related genes, CC patients were divided into three m7G clusters. Based on differentially expressed genes (DEGs) from the above three groups, CC patients were further divided into three gene clusters. The m7G score, a prognostic model, was established using principal component analysis (PCA) based on 15 prognosis-associated m7G genes. KM curve analysis demonstrated that the overall survival rate was remarkably higher in the high-m7G score group, which was much more significant in advanced CC patients as confirmed by subgroup analysis. Correlation analysis indicated that the m7G score was associated with tumor mutational burden (TMB), PD-L1 expression, immune infiltration, and drug sensitivity. The expression level of prognosis-related m7G genes was further confirmed in human CC cell lines and samples. This study established an m7G gene-based prognostic model (m7G score), which demonstrated the important roles of m7G-related genes during CC initiation and progression. The m7G score could be a practical biomarker to predict immunotherapy response and prognosis in CC patients.

Effect of oxaliplatin in elderly colon cancer patients with pathological T4 and/or N2 disease: a multicenter, propensity score-matched analysis.

Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence. This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70years, n = 197) and a young group (< 70years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched. Before matching, the rates of poor performance status (p < 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p < 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p < 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p < 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients. The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.

Is Laparoscopic Complete Mesocolic Excision and Central Vascular Ligation Really Necessary for All Patients With Right-Sided Colon Cancer?

Colon cancer treatment is on the way to evolution over several decades. The minimally invasive surgery has improved postoperative short-term outcomes. Adjuvant chemotherapy has prolonged the survival of advanced colon cancer patients. Hohenberger proposed the noble concept of complete mesocolic excision (CME) which consists of 3 components: plane surgery, sufficient longitudinal bowel resection, and central vascular ligation (CVL). Mesocolic plane surgery shares the same surgical principle of total mesorectal excision, which is maintaining the intact mesothelial envelope. However, there remain debates about the extent of bowel resection and the level of CVL for maximizing lymph node dissection. There is no solid clinical evidence for the oncological necessity and benefit of extended radical dissection in right hemicolectomy. CME with CVL based on open surgery has been adopted in laparoscopic surgery. So, it is also necessary to look at how the CME could be transformed and successfully implanted in the laparoscopic era. Recent rapid advances in surgical technology and cancer biology are preparing for fundamental changes in cancer surgery. In this study, we reviewed the history, oncological necessity, and compatibility of CME for the right hemicolectomy in the laparoscopic era and outline the new perspectives on the evolution of cancer surgery.

Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion &gt; 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients

Differences in effectiveness and use of laparoscopic surgery in locally advanced colon cancer patients

Patients with locally advanced colon cancer have worse outcomes. Guidelines of various organizations are conflicting about the use of laparoscopic colectomy (LC) in locally advanced colon cancer. We determined whether patient outcomes of LC and open colectomy (OC) for locally advanced (T4) colon cancer are comparable in all colon cancer patients, T4a versus T4b patients, obese versus non-obese patients, and tumors located in the ascending, descending, and transverse colon. We used data from the 2013–2015 American College of Surgeons’ National Surgical Quality Improvement Program. Patients were diagnosed with nonmetastatic pT4 colon cancer, with or without obstruction, and underwent LC (n = 563) or OC (n = 807). We used a composite outcome score (mortality, readmission, re-operation, wound infection, bleeding transfusion, and prolonged postoperative ileus); length of stay; and length of operation. Patients undergoing LC exhibited a composite outcome score that was 9.5% lower (95% CI − 15.4; − 3.5) versus those undergoing OC. LC patients experienced a 11.3% reduction in postoperative ileus (95% CI − 16.0; − 6.5) and an average of 2 days shorter length of stay (95% CI − 2.9; − 1.0). Patients undergoing LC were in the operating room an average of 13.5 min longer (95% CI 1.5; 25.6). We found no evidence for treatment heterogeneity across subgroups (p > 0.05). Patients with locally advanced colon cancer who receive LC had better overall outcomes and shorter lengths of stay compared with OC patients. LC was equally effective in obese/nonobese patients, in T4a/T4b patients, and regardless of the location of the tumor.

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy

ABSTRACT Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, represented by progression-free survival (PFS) and overall survival (OS), of combined chemotherapy and adoptive cellular therapy (ACT) in advanced colon cancer patients. Plasma was collected from colorectal cancer patients (CRC) treated with either chemotherapy alone (oxaliplatin and capecitabine) (XELOX CT alone group, n = 19), or ACT with a mixed dendritic cell/cytokine-induced killer cell product (DC-CIK) + XELOX (ICT group, n = 20). Circulating microbiota analysis was performed by PCR amplification and next-generation sequencing of variable regions V3~V4 of bacterial 16S rRNA genes. The association of the blood microbial diversity with clinical response to the therapy as measured by RECIST1.1 and OS was evaluated. The baseline Chao index of blood microbial diversity predicted prolonged PFS and OS of DC/CIK immunotherapy. More diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified among responders to DC/CIK compared with non-responders. The plasma bacterial DNA copy number is inversely correlated with the CD3−/CD16+/CD56+ NK cells in circulation and decreased following DC-CIK; however, the Chao index of plasma microbiota significantly increased after administration of the DC-CIK product and this subsequent change was correlated with the number of CD3−/CD16+/CD56+ and CD8+/CD28+ cells infused. The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK. Cellular immunotherapy can affect the plasma microbiota’s diversity in a manner favorable to clinical responses.

Neoadjuvant Short-course Radiotherapy or Concurrent Chemoradiotherapy Followed by Radical Colectomy in Locally Advanced Colon Cancer Patients

Neoadjuvant Short-course Radiotherapy or Concurrent Chemoradiotherapy Followed by Radical Colectomy in Locally Advanced Colon Cancer Patients

Pharmacokinetically-guided preoperative FOLFOX chemotherapy for locally advanced colon cancer patients.

4104 Background: Preliminary results from ongoing randomised trials suggest that neoadjuvant chemotherapy (NAC) may be an alternative approach to conventional adjuvant therapy. We assessed the feasibility and activity of incorporating a pharmacokinetically (PK) guided dose adjustment of 5-FU within preoperative Folfox. Methods: Radiologically staged LACC pts, T4 or T3 with extramural depth &gt;5mm beyond the muscularis propia, were planned to receive 4-6 biweekly cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and subsequent cycles tailored according to PK monitoring in order to reach a target 5-FU area under the curve (AUC) between 20-30 mg∙h∙L-1). Dihidrouracil deshidrogenase was determined before the first cycle in order to detect pts with 5-Fu intolerance. Three serum samples were obtained during the 5-Fu infusion in the first two cycles. Pathological tumor regression was graded according to the MSKCC classification and toxicity to the NCI-CTCAE 4.0. Results: From June 2012 to August 2017, 45 pts (M/F: 35/10; median age 63) with LACC (T3: 66.7%; T4: 31.1%; T2: 2.2%; N+:66.6%) were evaluated. Median dose of 5-FU was 4500 mg. 48.9% of the pts required a 5-FU dose increase to reach the target AUC. Side effects profile included G3 neutropenia (3 pts), G2 diarrhea (2 pts) and G2 asthenia (9 pts). NAC was discontinued in 3 pts due to small bowell obstruction requiring surgery (no progressive disease during NAC). R0 resection rate was 100% (93.3% laparoscopy-assited). MSKCC score included grades 4, 3+ and 3 in 11.1%, 26.7% and 28.9% of pts, respectively. A complete pathological response was found in 5 pts (11.1%). Median number of harvested nodes was 16 (7-51), 80% ypN0. Those pts with AUC 25-30 had a 3-fold higher likelihood of achieving a MSKCC 3, 3+ and 4 responses. Median time to hospital discharge was 7 days (range 4-22). After a median follow-up of 60 months (44-66), 5-year actuarial PFS is 88.8%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts is safe and well tolerated, achieving remarkable rates of major pathological responses and R0 resections.

An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer

Systemic inflammation is present during and serves as a diagnostic tool for cancer-associated cachexia and is detrimental to serum 25-hydroxyvitamin D (25(OH)D) concentrations in non-cancer conditions. The neutrophil-to-lymphocyte ratio (NLR) is a desirable measure of systemic inflammation because it is easily calculated from a routine complete blood cell count with differentials. We sought to determine if an elevation in the NLR associates with greater weight loss, cachexia, and lower serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with advanced cancer. Advanced colon, lung, and prostate cancer patients (stages III/IV; n = 50) were retrospectively studied and separated into one of two groups: 1) Above (n = 25) or 2) Below (n = 25) the median NLR of 3.15 determined at diagnosis. Around the time of diagnosis, serum 25(OH)D and body weight were assessed, while body weight was assessed again at a later date. Weight loss and cachexia were significantly (both p < 0.05) greater and there was a trend (p < 0.10) for lower serum 25(OH)D concentrations in the Above group. We conclude that an elevation in the NLR associates with greater weight loss and cachexia, and potentially, a lower serum 25(OH)D concentration in patients with advanced colon, lung, or prostate cancer.

The Prognostic Value of G1 Cyclins, p21 and Rb Protein in Patients With Colon Cancer.

Cyclins D1 and E play different roles in the cell cycle. Cyclin E promotes chromosome instability, whereas cyclin D1 regulates apoptosis of cells. This study evaluated the prognostic significance of G1 cyclins, p21 and pRb in tumor proliferation. A total of 102 patients with colon cancer were operated on and staged according to TNM. Follow-up was 2 to 68 months (mean 38.3±16.7 months). Expression of cyclin E and D1 were evaluated using immunohistochemistry. Levels of cyclin E expression were correlated with cyclin D1 expression (p=0.038), p21 expression (p=0.047), and pRb expression (p=0.004). The 5-year survival rate along with prognosis of patients with advanced stage (III, IV) colon cancer and cyclin D1 positive tumors, were significantly worse (p=0.009). Statistically significant association was observed between tumor proliferative capacity Ki-67, cyclin D1 (p=0.009), pRb (p=0.031) and p21 (p=0.050). Cyclin D1 is highly expressed in advanced stage colon cancer patients, implying a potential prognostic value.

Kolorektal kanserde primer tümör lokalizasyonunun tüm evrelerdeki etkileri

Abstract: Purpose : The aim of this study was to examine the effects of tumor localization in early and advanced stage colon cancer patients. Materials and Methods : This retrospective study enrolled 249 primary colorectal cancer (CRC) patients at medical oncology department of Adnan Menderes University between 2013-2017. Results: In early stage, left sided tumors were significantly more common in males(p=0.027). In right sided tumours recurrence developed earlier in female patients(p=0.043) and female sex,young age were unfavorable prognostic factors for the relapse time. Positive and unknown PANRAS mutation status were found to be unfavorable prognostic factors for both side. In metastatic stage, patients with PANRAS mutant left sided tumors lived longer than PANRAS negative patients (49.0 vs 25.5 months respectively, p <0.001). OS was 11 months and PFS was 1.8 months longer with anti-EGFR agents than anti-VEGFR agents, in right sided tumors.In left sided tumors, there was no difference, only PFS was longer with anti-VEGFR agents(13 months vs 6.3 months). In PANRAS positive patients, OS and PFS were longer with anti-VEGFR treatment in the left side tumors(OS 49.0 months vs 30.6 months PFS, 13.2 months vs 7.2 months, p=0.784). Conclusions: In our study, the efficacy results of the treatment which was given according to the primary tumor location were not compatible with the literature. Primer tumor location is a transition period for understanding of molecular subtypes at the colon cancer. The on-going studies of genomic differences between right and left sided tumors will able to better clarifying of the biologic explanation of the observed difference.

Racial/ethnic disparities in the adjuvant chemotherapy of locally advanced colon cancer patients

BackgroundMost race/ethnicity-oriented investigations focus on Caucasian Americans (whites) and African Americans (blacks), leaving Asians, Hispanic white (Hispanics), and other minorities less well studied. Adjuvant chemotherapy (CT) after curative resection is critical to patients with locally advanced colon cancer (LACC). We studied the racial disparities in the adjuvant CT of LACC to aid in selecting optimal treatments for people from different races/ethnicities in this era of precision medicine. MethodsPatients with American Joint Committee on Cancer (AJCC) stage II or III colon cancer (CC) (together termed as LACC) were included based on Surveillance, Epidemiology, and End Results cancer registry–Medicare linked databases. The log-rank test and Cox multivariate regression analysis were performed to investigate the racial/ethnic disparities in cohorts divided according to the regimen of adjuvant CT. ResultsIn the LACC patients who did not receive adjuvant CT, Asian patients had better survival than other groups (all, P <0.05). For the fluoropyrimidine cohort, the survival of Asian patients was better than that of whites, blacks, and other minorities (all, P <0.05). For the fluoropyrimidine with oxaliplatin cohort, other minorities had superior survival to other groups (all, P <0.05). Similar findings were demonstrated for patients with AJCC stage II and III CC, and the observed better survival persisted after adjustments in the Cox models. ConclusionsAmong LACC patients not receiving adjuvant CT, Asians achieved better survival than other races/ethnicities. Superior survival was also observed for Asians in the fluoropyrimidine cohort and for other minorities in the fluoropyrimidine with oxaliplatin cohort for AJCC stage III CC.

Polymorphisms in the ICOS/CD28-ICOSL pathway are related to capecitabine-based chemotherapy response in advanced colon cancer patients

Polymorphisms within a gene’s 3′-UTR may modulate posttranscriptional regulation of gene expression, and may explain individual sensitivity of chemotherapy. To investigate the correlation between single nucleotide polymorphisms (SNPs) in 3′-UTRs of B7/CD28 family genes and the response of capecitabine-based chemotherapy in colon cancer, 16 SNPs were identified in 274 advanced colon cancer patients. Statistical analysis indicated that ICOS rs1559931, rs4404254, and rs4675379 were in complete linkage disequilibrium and significantly associated with chemotherapy response. Heterozygous patients with rs1559931 G/A (31.34% vs 48.29%; P = 0.016), rs4404254 T/C (30.43% vs 48.77%; P = 0.011), or rs4675379 G/C (28.13% vs 49.04%; P = 0.004) genotypes showed poorer response to chemotherapy compared to wildtype patients. Moreover, three SNPs, including ICOSL rs15927, ICOSL rs3804033 and CD28 rs3181113, were significantly associated with the occurrence of side effects of chemotherapy. In addition, patients with ICOSL rs15927 G/G (78.26%), ICOSL rs3804033 G/G (76.00%), or CD28 rs3181113 T/T (82.05%) were more prone to enduring adverse events compared to patients bearing other polymorphisms. Taken together, our findings demonstrated that polymorphisms in the 3′-UTRs of genes in the ICOS/CD28-ICOSL pathway may influence the efficacy and occurrence of adverse events of capecitabine-based chemotherapy in advanced colon cancer patients.

The SNPs in pre-miRNA are related to the response of capecitabine-based therapy in advanced colon cancer patients.

The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C allele carriers (39.69%) were apparently less than that of the G/G homozygous patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138 were significantly associated with the occurrence of side effects of chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T allele (OR = 2.299) were much more prone to endure adverse events. However, the incidence of side effect was lower in the patients carrying rs73239138 A allele than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic variations in pre-miRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients.

Phthalate exposure promotes chemotherapeutic drug resistance in colon cancer cells.

Phthalates are widely used as plasticizers. Humans can be exposed to phthalates through ingestion, inhalation, or treatments that release di(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono(2-ehylhexyl) phthalate (MEHP), into the body from polyvinyl chloride-based medical devices. Phthalate exposure may induce reproductive toxicity, liver damage, and carcinogenesis in humans. This study found that colon cancer cells exposed to DEHP or MEHP exhibited increased cell viability and increased levels of P-glycoprotein, CD133, Bcl-2, Akt, ERK, GSK3β, and β-catenin when treated with oxaliplatin or irinotecan, as compared to control. The P-glycoprotein inhibitor, tariquidar, which blocks drug efflux, reduced the viability of DEHP- or MEHP-treated, anti-cancer drug-challenged cells. DEHP or MEHP treatment also induced colon cancer cell migration and epithelial-mesenchymal transformation. Elevated stemness-related protein levels (β-catenin, Oct4, Sox2, and Nanog) and increased cell sphere sizes indicated that DEHP- or MEHP-treated cells were capable of self-renewal. We also found that serum DEHP concentrations were positively correlated with cancer recurrence. These results suggest phthalate exposure enhances colon cancer cell metastasis and chemotherapeutic drug resistance by increasing cancer cell stemness, and that P-glycoprotein inhibitors might improve outcomes for advanced or drug-resistant colon cancer patients.