scholarly journals Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery

2017 ◽  
Author(s):  
Yue Hu ◽  
Jochen Gaedcke ◽  
Georg Emons ◽  
Tim Beissbarth ◽  
Marian Grade ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Susceptibility ◽  
Disease Free Survival ◽  
Colorectal Cancer Risk ◽  
Cancer Prognosis ◽  
Disease Free

AbstractBackgroundColorectal cancer (CRC) is among the leading causes of cancer death. Rectal cancers account for one third of CRC cases. The role and significance of colorectal cancer risk loci in rectal cancer progression has not been investigated.MethodsWe generated and explored a dataset from 230 rectal cancer patients by gene expression microarray analysis of cancer samples and matched controls, and SNP arrays of germline DNA.Results8q24 (upstream of MYC) and 18q21 (in the intron of SMAD7), two of the loci most strongly linked with colorectal cancer risk, as well as 20q13 (in the intron of LAMA5), are tightly associated with the prognosis of rectal cancer patients. For SNPs on 18q21 (rs12953717 and rs4464148) and 20q13 (rs4925386), alleles that correlate with higher risk for the development of colorectal cancer are associated with shorter disease free survival. However, for rs6983267 on 8q24, the low risk allele is associated with a higher risk for recurrence and metastasis after surgery, and importantly, is strongly correlated with the resistance of colorectal cancer cell lines to chemoradiotherapy. We also found that although MYC expression is dramatically increased in cancer, patients with higher levels of MYC have a better prognosis. The expression of SMAD7 is weakly correlated with disease free time. Notably, the presence of the 8q24 and 18q21 SNP alleles is not correlated with a change of expression of MYC and SMAD7. rs4464148, and probably rs6983267 and rs4925386, are linked with overall survival time of patients.ConclusionsSNPs at three colorectal cancer risk loci detect subpopulations of rectal cancer patients with poor prognosis. rs6983267 probably affects prognosis through interfering with the resistance of cancer cells to chemoradiotherapy.

scholarly journals Elevated Soluble Galectin-3 as a Marker of Chemotherapy Efficacy in Breast Cancer Patients: A Prospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Arooj Shafiq ◽  
January Moore ◽  
Aliya Suleman ◽  
Sabeen Faiz ◽  
Omar Farooq ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Residual Tumor ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Galectin 3 ◽  
Chemotherapy Efficacy ◽  
Disease Free

Purpose. Galectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3. Methods. Breast cancer patients with first time cancer diagnosis and no prior treatment (n=88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA, respectively. Healthy women (>18 years of age, n=63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease-free survival analysis. Results. Enhanced levels of plasma (adjuvant) and stromal (neoadjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy-induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion. Conclusion. The findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors postchemotherapy can also be used to predict long-term prognosis in patients.

Multicenter phase II trial of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer with a T3/T4 tumor FACT trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 713-713
Author(s):  
Toshiyuki Enomoto ◽  
Yoshihisa Saida ◽  
Kazuhiro Takabayashi ◽  
Jiro Nagao ◽  
Junichi Koike ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Response Rate ◽  
Disease Free Survival ◽  
Stage Ii ◽  
R0 Resection ◽  
Free Survival ◽  
Disease Free

713 Background: The efficacy and safety of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer patients with a T3/T4 tumor is still unknown. Methods: Inclusion criteriain this study are as follows: Stage II/III (Ra/Rb) rectal cancer patients with a T3/T4 tumor. The primary endpoint is preoperative response rate, and the secondary endpoints are histological effect, R0 resection rate, pCR rate, down-staging rate, neoadjuvant therapy completion rate, toxicity, the incidence of postoperative complications, and 3-year disease-free survival. Computed tomography was performed after 4 courses of mFOLFOX6. Patients with disease progression (DP) underwent resection of the primary lesion, while those without DP received another 2 courses of treatment. Treatment was discontinued when resection was not possible in patients with DP. Results: Registered patients totaled 53 with a mean age of 60 (38–77). The number of patients with T3 and T4 tumors was 42 and 10, and patients at stages II and III were 10 and 42, respectively. One patient withdrew due to consent retraction. Median relative dose intensity of mFOLFOX6 therapy was 93.2% for L-OHP, 5-FU, and l-LV. Treatment completion was achieved in 96.2% and 84.6% for 4 and 6 courses, respectively, and withdrawal was due to patient’s discretion, not adverse events. Preoperative response rate was 51%. Surgery was performed in 78.8% of patients. Serious (grade ≥3) toxicity included neutropenia (n=5), leukopenia (n=1), thrombocytopenia (n=1), febrile neutropenia (n=1), nausea (n=1), vomiting (n=1), and peripheral neuropathy (n=2). The rates of R0 resection, pCR, and sphincter preservation were 91.0%, 10.3%, and 82.9%. The down staging rate was calculated as 2%. The median follow-up after surgery was 18.0 months. Median DFS was 17.3 months, and 1-year disease-free survival was 78.8%. Median OS was 22.0 months, and 1-year overall survival was 95.7%. Postoperative complications included suture failure (n=3), wound infection (n=2), pneumonia (n=1), and intestinal obstruction (n=1). Conclusions: Neoadjuvant chemotherapy using mFOLFOX6 is a safe and efficacious treatment option for rectal cancer, especially locally advanced disease. Clinical trial information: UMIN000006583.

scholarly journals Colorectal cancer susceptibility loci as predictive markers of rectal cancer prognosis after surgery

2017 ◽  
Vol 57 (3) ◽  
pp. 140-149 ◽  
Author(s):  
Yue Hu ◽  
Jochen Gaedcke ◽  
Georg Emons ◽  
Tim Beissbarth ◽  
Marian Grade ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Cancer Susceptibility ◽  
Predictive Markers ◽  
Cancer Prognosis ◽  
Susceptibility Loci

Predictors of disease-free survival in rectal cancer patients undergoing curative proctectomy

2008 ◽  
Vol 10 (9) ◽  
pp. 879-886 ◽  
Author(s):  
D. Stewart ◽  
Y. Yan ◽  
M. Mutch ◽  
I. Kodner ◽  
S. Hunt ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals Folate pathway genes linked to mitochondrial biogenesis and respiration are associated with outcome of patients with stage III colorectal cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Author(s):  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Mitochondrial Biogenesis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Folate Pathway ◽  
Colorectal Cancer Patients ◽  
Disease Free

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.

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