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Predictive and prognostic markers in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States, with an estimated 153,760 new cases predicted for 2007. Since the 1960s, 5-fluorouracil (5-FU) has remained the mainstay of therapeutic options in the treatment of advanced CRC, with response rates of 20% to 25%. The introduction of newer agents such as oxaliplatin and irinotecan in combination with 5-FU has increased response rates to 40% to 50% in advanced disease and improved overall survival. The development of monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor has demonstrated additional clinical benefit for patients with metastatic disease. However, many patients succumb to their disease, and a significant proportion will experience severe chemotherapy-associated toxicities while deriving little or no benefit. To improve the treatment of CRC, efforts must be directed toward the identification of patients who are likely to respond to a specific therapy, those who will experience severe toxicities, and those who will benefit from chemotherapy in the adjuvant setting. However, the utility of individual markers of response, toxicity, and disease recurrence remains in question. Efforts are now under way to develop multimarker profiles that can more accurately predict disease response. In this review, we discuss both predictive and prognostic markers identified in the treatment of CRC in terms of their robustness and their ability to assist the clinician in developing the most efficacious and least toxic therapeutic strategy for each patient.

SUBMITTER: Wilson PM

PROVIDER: S-EPMC2631215 | biostudies-other | 2007 Nov

REPOSITORIES: biostudies-other

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Predictive and prognostic markers in colorectal cancer.

Wilson Peter M PM Ladner Robert D RD Lenz Heinz-Josef HJ

Gastrointestinal cancer research : GCR 20071101 6

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States, with an estimated 153,760 new cases predicted for 2007. Since the 1960s, 5-fluorouracil (5-FU) has remained the mainstay of therapeutic options in the treatment of advanced CRC, with response rates of 20% to 25%. The introduction of newer agents such as oxaliplatin and irinotecan in combination with 5-FU has increased response rates to 40% to 50% in advanced disease and improved overal ...[more]

PMID: 19262902

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Project description:BackgroundColorectal cancer (CRC) is a common malignant solid tumor with an extremely low survival rate after relapse. Previous investigations have shown that autophagy possesses a crucial function in tumors. However, there is no consensus on the value of autophagy-associated genes in predicting the prognosis of CRC patients. This work screens autophagy-related markers and signaling pathways that may participate in the development of CRC, and establishes a prognostic model of CRC based on autophagy-associated genes.MethodsGene transcripts from the TCGA database and autophagy-associated gene data from the GeneCards database were used to obtain expression levels of autophagy-associated genes, followed by Wilcox tests to screen for autophagy-related differentially expressed genes. Then, 11 key autophagy-associated genes were identified through univariate and multivariate Cox proportional hazard regression analysis and used to establish prognostic models. Additionally, immunohistochemical and CRC cell line data were used to evaluate the results of our three autophagy-associated genes EPHB2, NOL3, and SNAI1 in TCGA. Based on the multivariate Cox analysis, risk scores were calculated and used to classify samples into high-risk and low-risk groups. Kaplan-Meier survival analysis, risk profiling, and independent prognosis analysis were carried out. Receiver operating characteristic analysis was performed to estimate the specificity and sensitivity of the prognostic model. Finally, GSEA, GO, and KEGG analysis were performed to identify the relevant signaling pathways.ResultsA total of 301 autophagy-related genes were differentially expressed in CRC. The areas under the 1-year, 3-year, and 5-year receiver operating characteristic curves of the autophagy-based prognostic model for CRC were 0.764, 0.751, and 0.729, respectively. GSEA analysis of the model showed significant enrichment in several tumor-relevant pathways and cellular protective biological processes. The expression of EPHB2, IL-13, MAP2, RPN2, and TRAF5 was correlated with microsatellite instability (MSI), while the expression of IL-13, RPN2, and TRAF5 was related to tumor mutation burden (TMB). GO analysis showed that the 11 target autophagy genes were chiefly enriched in mRNA processing, RNA splicing, and regulation of the mRNA metabolic process. KEGG analysis showed enrichment mainly in spliceosomes. We constructed a prognostic risk assessment model based on 11 autophagy-related genes in CRC.ConclusionA prognostic risk assessment model based on 11 autophagy-associated genes was constructed in CRC. The new model suggests directions and ideas for evaluating prognosis and provides guidance to choose better treatment strategies for CRC.

Project description:To evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) and other clinicopathological factors in patients undergoing curative resection of colon cancer.183 patients with histologically proven colorectal cancer who had undergone potentially curative resection between 2010 and 2016 at Ankara Numune Training and Research Hospital were retrospectively analyzed and clinicopathological characteristics included age, sex, tumor type, grade, size and localization, the number of metastatic and total number of lymph nodes removed, vascular and perineural invasion of the tumor, TNM stages, tumor marker levels (CEA, CA19-9, AFP, CA-125, CA15-3), complete blood counts, albumin levels, overall survival (months), NLR, PLR, LMR and PNI ratios were retrospectively reviewed and analyzed from the electronic database. The primary outcome measure was overall survival.Regarding overall survival, on univariate analysis the following variables were significantly associated with poor outcome following resection: T-stage (P = 0.037), lymph node invasion (P = 0.037), cancer stage (P = 0.034), CEA (P = 0.042), CA19-9 (P = 0.004), and PNI (P = 0.001). To evaluate the independent prognostic value, multivariate Cox proportional hazard analysis to control for other prognostic factors was used. Using cancer-specific death as an end point for NLR, PLR, LMR, PNI and CA19-9 the optimal cut off values were calculated by ROC analysis. Regarding overall survival, on multivariate analysis high CA19-9 (HR = 1.001, 95%CI: 1.00-1.002, P = 0.012) and low PNI (HR = 0.938, 95%CI: 0.891-0.987, P = 0.014) were the only variables independently associated with shortened overall survival. Patients with a PNI < 35 had a median OS of 52.25 mo. In contrast, patients with an PNI > 35 had a median OS of 66 mo. Patients with a CA 19-9 < 17 had a median OS of 66 mo and in patients with a CA19-9 > 17 had a median OS of 53.76 mo.This study shows that decrease in the PNI and increase in CA 19-9 is associated with poor survival in patients with resectable colon cancer.

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Predictive and prognostic markers in colorectal cancer.

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Predictive and prognostic markers in colorectal cancer.

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