Karyopherin alpha 2 expression is a novel diagnostic and prognostic factor for colorectal cancer

PurposeActivating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies.Patients and MethodsThe Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry.ResultsThree hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P < .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012).ConclusionKRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.

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Unresected hepatic metastases (HM) from colorectal cancer (CRC). Prospective prognostic factor analysis on 544 cases from fondation Française de cancerologie digestive (FFCD)

European Journal of Cancer ◽

10.1016/0959-8049(93)91093-z ◽

1993 ◽

Vol 29 ◽

pp. S89

Author(s):

Ph. Rougier ◽

Ch. Milan ◽

L. Bedenne ◽

F. Lazorthes ◽

G. Fourtanier ◽

...

Keyword(s):

Colorectal Cancer ◽

Factor Analysis ◽

Prognostic Factor ◽

Hepatic Metastases ◽

Cancérologie Digestive

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618 POSTER Lymph node ratio as prognostic factor in node-positive colorectal cancer

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(05)80914-0 ◽

2005 ◽

Vol 3 (2) ◽

pp. 174

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Prognostic Factor ◽

Lymph Node Ratio ◽

Node Positive ◽

Node Ratio

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DPYD c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer

Genetic Testing and Molecular Biomarkers ◽

10.1089/gtmb.2020.0285 ◽

2021 ◽

Vol 25 (4) ◽

pp. 276-283

Author(s):

Adem Deligonul ◽

Secil Aksoy ◽

Gulcin Tezcan ◽

Berrin Tunca ◽

Ozkan Kanat ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

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Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

10.21203/rs.3.rs-45688/v1 ◽

2020 ◽

Author(s):

Hou-Qun Ying ◽

Fan Sun ◽

Wei Wang ◽

Dan Cai ◽

Ying Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Chronic Inflammation ◽

Clinical Outcomes ◽

Cox Regression ◽

Independent Prognostic Factor ◽

Low Grade ◽

Albumin Ratio ◽

Response To Chemotherapy ◽

Chemotherapy Efficacy

Abstract Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.

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