Prognostic Value Of KRAS Mutations Research Articles

Prognostic Value of KRAS Mutations in Relation to PDL1 Expression and Immunotherapy Treatment in Adenocarcinoma and Squamous Cell Carcinoma Patients: A Greek Cohort Study.

Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1 > 49% in combination with a negative KRAS result had a median overall survival of 40 months compared to patients with a positive KRAS result (9 months, p < 0.05). In addition, patients diagnosed with adenocarcinoma, PDL1 < 49% and negative KRAS result had a median overall survival of 39 months compared to patients with a positive result (28 months, p < 0.05). Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Assessing the prognostic value of KRAS mutation combined with tumor size in stage I-II non-small cell lung cancer: a retrospective analysis.

KRAS mutation status is a well-established independent prognostic factor in advanced non-small cell lung cancer (NSCLC), yet its role in early-stage disease is unclear. Here, we investigate the prognostic value of combining survival data on KRAS mutation status and tumor size in stage I-II NSCLC. We studied the combined impact of KRAS mutational status and tumor size on overall survival (OS) in patients with stage I-II NSCLC. We performed a retrospective study including 310 diagnosed patients with early (stage I-II) NSCLCs. All molecularly assessed patients diagnosed with stage I-II NSCLC between 2016-2018 in the Västra Götaland Region of western Sweden were screened in this multi-center retrospective study. The primary study outcome was overall survival. Out of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in the KRAS gene. Our study confirmed staging and tumor size as prognostic factors. However, KRAS mutational status was not found to impact OS and there was no difference in the risk of death when combining KRAS mutational status and primary tumor size. In our patient cohort, KRAS mutations in combination with primary tumor size did not impact prognosis in stage I-II NSCLC.

A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation.

Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

Prognostic value of KRAS mutations, TP53 mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy

AimsThe aim of this study was to investigate the association between oncogenic alterations and programmed cell death ligand 1 (PD-L1) expression in lung adenocarcinomas, as well as the prognostic value...

Prognostic Value of KRAS Mutations in Colorectal Cancer Patients.

Simple SummaryKirsten rat sarcoma viral oncogene homolog (KRAS)-mutated colorectal cancer (CRC) seems to have a different biological behavior and therapeutic approach compared with non-KRAS mutated CRC. Except for the proven predictive significance of KRAS mutations in CRC patients, their prognostic significance is still under evaluation. Our study shows that 93.2% of RAS-mutated patients were KRAS mutants, with G12D being the most common subtype. KRAS G12D mutation is correlated with better overall survival (OS). KRAS G12C mutations may indicate worse prognosis regarding progression free (PFS) and OS, as well as exon 4 and exon 3 KRAS mutations for PFS and OS, respectively. Further studies are warranted to confirm these results.Colorectal cancer (CRC) remains a major public health issue. The detection of parameters that affect CRC prognosis is of great significance. KRAS mutations, play a crucial role in tumorigenesis with a strong predictive value. KRAS-mutated stage-IV CRC patients gain no benefit of the anti-EGFR therapy. The KRAS G12C mutation subtype is under investigation for treatment regimens. The present study aimed to detect various RAS mutations in a cohort of 578 RAS-mutated CRC patients; 49% of them had de novo metastatic disease; 60% were male; 71.4% had left-sided tumors; and 94.6% had a good performance status. KRAS mutations were detected in 93.2% of patients, with KRAS G12D being the most common subtype (30.1%). KRAS mutations presented shorter progression-free (PFS) and overall survival (OS), compared with NRAS mutations, although not significantly (PFS: 13.8 vs. 18.5 months; p = 0.552; OS: 53.1 vs. 60.9 months; p = 0.249). KRAS G12D mutations presented better OS rates (p = 0.04). KRAS G12C mutation, even though not significantly, presented worse PFS and OS rates. KRAS exon 3 and 4 mutations presented different PFS and OS rates, although these were not significant. Concluding, KRAS G12D and G12C mutations lead to better and worst prognosis, respectively. Further studies are warranted to validate such findings and their possible therapeutic implication.

The prognostic value of KRAS mutation in locally advanced rectal cancer.

The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6months and 76.3months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Prognostic Value of KRAS Mutations in the Peripheral Blood of Patients with Pancreatic Cancer: a Systematic Review and Meta-analysis

Prognostic Value of KRAS Mutations in the Peripheral Blood of Patients with Pancreatic Cancer: a Systematic Review and Meta-analysis

Age-dependent prognostic value of KRAS mutation in metastatic colorectal cancer.

Background: The age-dependent prognostic impact of KRAS status in metastatic colorectal cancer (mCRC) is unknown. Materials & Methods: We used the National Cancer Database to evaluate the survival by KRAS status for age-groups <50, 50-69and ≥70, adjusting for relevant patient and tumor characteristics. Results: mCRC patients (n =26,095;33.5%) had KRAS status reported, and 11,338 of these patients (43.4%) had mutations in the KRAS gene. Patients with KRAS mutations had worse overall survival than wild-type KRAS patients. In age-groups <50years (23 vs29months;p<0.001) and 50-69 (21 vs23.4months;p<0.001), KRAS mutations were significantly associated with worse survival, whereasin the ≥70-year age-group, there was no significant association (14 vs 14months;p=0.34). Conclusion: We conclude that the age of patients influences the prognostic value of KRAS mutation in metastatic colorectal cancer.

Prognostic value of KRAS mutation in patients undergoing pulmonary metastasectomy for colorectal cancer: A systematic review and meta-analysis.

The purpose of the study was to evaluate whether KRAS mutation could be an independent prognostic biomarker in patients undergoing pulmonary metastasectomy (PM) for colorectal cancer (CRC). A systemic review was performed by searching online databases to identify studies reporting overall survival (OS) and recurrence free survival (RFS) of CRC patients undergoing PM. Pooled HRs were calculated for OS and RFS. A total of 15233 patients from 60 studies were included. Pooled analysis showed that KRAS mutation was associated with worse OS (HR: 1.86, 95 % Cl: 1.35-2.57) and RFS (HR: 1.68, 95 % Cl: 1.38-2.04). A significant effect on OS and/or RFS was also shown by other 18 factors. This meta-analysis found that KRAS mutation is an important prognostic predictor for OS and RFS in CRC patients undergoing PM, supporting a comprehensive model including clinicopathological and biological factors for optimal patients selection and prognosis for surgical treatment.

Age-dependent prognostic value of KRAS mutation in metastatic colon cancer.

e16085 Background: KRAS mutation is associated with poor prognosis in metastatic colon cancer (mCC). However, the age-dependent prognostic value of KRAS status is unknown. We aimed to confirm if the prognostic impact of KRAS is dependent on the age of diagnosis in mCC. Methods: We identified adult patients with mCC diagnosed between 2004 and 2016 using the NCDB. We compared patients with KRAS mutation and KRAS wild type, stratified according to age group &lt; 50, 50-70, and ≥70. Categorical variables were compared using the chi-square test. We performed the Kaplan-Meier and Cox regression methods for survival analyses. We adjusted for patient and tumor characteristics (included KRAS status, MSI, 18q loss of heterozygosity, side of the primary tumor). Results: A Total of 19,875 patients had KRAS status reported; 43% had KRAS mutation, and 57% were KRAS wild type. Patients with KRAS mutation were more likely to be female, black, have elevated CEA, and have right-sided tumors (all p &lt; .001). In the overall population, patients with KRAS mutation had significantly worse OS compared to patients with KRAS wild type (20 vs. 22 months, p &lt; .001), and this difference was maintained after multivariable Cox regression analysis ( p &lt; .001) (Table). Young patients ( &lt; 50 years) with KRAS mutation had a worse prognosis than those with KRAS wild type in the tumor (23 vs. 29 months, p &lt; .001). KRAS status did not maintain its prognostic value among older age (≥70 years) patients (14 vs. 14 months, p = NS). Conclusions: In this analysis of a national cancer registry, we confirmed that KRAS mutation was an independent poor prognostic factor for mCC. This effect persisted after adjusting for patient and tumor characteristics, including sidedness and MSI status. However, we identified that this prognostic value of KRAS mutation is significant in young mCC patients &lt; 50 years, as compared to older patients. [Table: see text]

The prognostic value of KRAS mutation in locally advanced rectal cancer.

e15090 Background: The prognostic value and prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). Methods: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status.Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. Results: Of the 784 eligible patients, 506 and 278 were KRAS negative (KRAS-) and KRAS positive (KRAS+). Median survival was 63.6 months and 76.3 months for KRAS+ and KRAS-patients, with propensity adjusted 3 and 5-year survival of (79.9% vs. 83.6%) and (56.7% vs 61.9%) respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS+ disease was associated with poorer survival on unadjusted and propensity adjusted multivariable analyses (Table). Conclusions: Our analysis of KRAS+ LARC suggest that KRAS+ disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted. [Table: see text]

Diagnostic and prognostic value of KRAS mutations in circulating pancreatic ductal adenocarcinoma tumor DNA

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor and one of the most malignant tumors worldwide. Circulating tumor DNA (ctDNA) has significant diagnostic and prognostic value for cancer patients. Methods: Surgical specimens and plasma samples were obtained from a total of 35 patients with PDAC at the Peking University Cancer Hospital between June 2016 and May 2017. To investigate KRAS mutations (G12R, G12V or G12D) in plasma ctDNA, digital polymerase chain reaction (PCR) was performed on samples obtained from PDAC patients before and after surgical resection. Results: KRAS mutations (G12R, G12V or G12D) between surgical tissue DNA (tDNA) and preoperative plasma ctDNA (pre-ctDNA) were consistent in 27 of 35 samples (77.1%, kappa index =0.397, P=0.003). Moreover, pre-ctDNA and postoperative plasma ctDNA (post-ctDNA) showed statistically significant associations with CA19-9 levels before surgery (P=0.027 and P=0.003, respectively). In addition, the Kaplan-Meier univariate and Cox multivariate analysis revealed that pre-ctDNA (G12V), post-ctDNA (G12V), or pre-post ctDNA (G12V, G12D) might be independent prognostic factors for overall survival (OS) and progression-free survival (PFS). Conclusions: Analysis of pre-ctDNA, post-ctDNA, and pre-post ctDNA showed high PDAC diagnostic and prognostic potential in patients.

Diagnostic and prognostic value of KRAS mutations in circulating pancreatic ductal adenocarcinoma tumor DNA

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic tumor and one of the most malignant tumors worldwide. Circulating tumor DNA (ctDNA) has significant diagnostic and prognostic value for cancer patients.

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer.

KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, KRAS codon 12 mutations were more common in female patients (P<0.05). KRAS codon 13 mutations tended to arise in right-sided compared with left-sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with KRAS codon 12 wild-type, codon 12 mutations were markedly correlated with a poorer survival (log-rank P=0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1.069-5.004, P=0.03; HR=2.621, 95% CI=1.057-6.497, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples.

The prognostic value of KRAS mutation by cell-free DNA in cancer patients: A systematic review and meta-analysis.

KRAS mutation has been found in various types of cancer. However, the prognostic value of KRAS mutation in cell-free DNA (cfDNA) in cancer patients was conflicting. In the present study, a meta-analysis was conducted to clarify its prognostic significance. Literature searches of Cochrane Library, EMBASE, PubMed and Web of Science were performed to identify studies related to KRAS mutation detected by cfDNA and survival in cancer patients. Two evaluators reviewed and extracted the information independently. Review Manager 5.3 software was used to perform the statistical analysis. Thirty studies were included in the present meta-analysis. Our analysis showed that KRAS mutation in cfDNA was associated with a poorer survival in cancer patients for overall survival (OS, HR 2.02, 95% CI 1.63–2.51, P<0.01) and progression-free survival (PFS, HR 1.64, 95% CI 1.27–2.13, P<0.01). In subgroup analyses, KRAS mutation in pancreatic cancer, colorectal cancer, non-small cell lung cancer and ovarian epithelial cancer had HRs of 2.81 (95% CI 1.83–4.30, P<0.01), 1.67 (95% CI 1.25–2.42, P<0.01), 1.64 (95% CI 1.13–2.39, P = 0.01) and 2.17 (95% 1.12–4.21, p = 0.02) for OS, respectively. In addition, the ethnicity didn’t influence the prognostic value of KRAS mutation in cfDNA in cancer patients (p = 0.39). Prognostic value of KRAS mutation was slightly higher in plasma than in serum (HR 2.13 vs 1.65), but no difference was observed (p = 0.37). Briefly, KRAS mutation in cfDNA was a survival prognostic biomarker in cancer patients. Its prognostic value was different in various types of cancer.

Kras mutation is a marker of worse oncologic outcomes after percutaneous radiofrequency ablation of colorectal liver metastases.

BackgroundKras mutation has been associated with shorter overall survival and time to disease recurrence after resection of colorectal liver metastases (CLM). This study evaluated the prognostic value of Kras mutation in patients with CLM treated by percutaneous radiofrequency ablation (RFA).MethodsThis is an IRB waived retrospective analysis of the impact of KRAS mutation status on oncologic outcomes after CLM RFA. The endpoints were overall survival (OS), local tumor progression (LTP) rates, and incidence of new liver, lung, and peritoneal metastases. Survival times were calculated using Kaplan-Meier methodology from the time of RFA.ResultsThe study enrolled 97 patients. Kras exon 2 mutation was detected in 39% (38/97) of patients. On univariate analysis, Kras mutation (P=0.016) (HR: 1.8; 95% CI: 1.1 – 2.9) was a significant predictor of OS and retained significance on multivariate analysis. Kras mutation was a significant predictor of new liver metastases (P=0.037) (SHR: 2.0; CI: 1.0-3.7) and peritoneal metastases (P=0.015) (sHR: 3.0; 95% CI: 1.2-7.2) on multivariate analysis. Kras mutation was a significant predictor of LTP after RFA of CLM ablated with margins of 1-5 mm (P=0.018) (SHR: 3.0; 95% CI: 1.2-7.7) with an LTP rate of 80% (12/15) versus 41% (11/27) for wild type.ConclusionKras mutation is a significant predictor of overall survival, new liver, and peritoneal metastases after RFA of CLM. A minimal radiographic ablation margin ≥ 6 mm is essential for local tumor control especially for mutant CLM.

KRAS G12C mutation as a poor prognostic marker of pemetrexed treatment in non-small cell lung cancer.

Background/AimsThe predictive and prognostic value of KRAS mutation and its type of mutations in non-small cell lung cancer (NSCLC) are controversial. This clinical study was designed to investigate the predictive value of KRAS mutations and its mutation types to pemetrexed and gemcitabine based treatment.MethodsAdvanced NSCLC patients tested for KRAS mutation (n = 334) were retrospectively reviewed and 252 patients with wild type epidermal growth factor receptor and no anaplastic lymphoma kinase fusion were enrolled for the analysis. KRAS mutations were observed in 45 subjects with mutation type as followed: G12C (n = 13), G12D (n = 12), G12V (n = 12), other (n = 8). Response rate (RR), progression-free survival (PFS), and overall survival (OS) of pemetrexed singlet and gemcitabine based chemotherapy were analysis.ResultsAge, sex, performance status were well balanced between subjects with or without KRAS mutations. No difference was observed in RR. Hazard ratio (HR) of PFS for pemetrexed treated subjects with G12C mutation compared to subjects with KRAS wild type was 1.96 (95% confidential interval [CI], 1.01 to 3.79; p = 0.045), but other mutations failed to show clinical significance. By analysis done by PFS, compared to the subjects with transition mutation, HR was 1.48 (95% CI, 0.64 to 3.40; p = 0.360) for subjects with transversion mutation on pemetrexed treatment and 0.41 (95% CI, 0.19 to 0.87; p = 0.020) for subjects treated with gemcitabine based chemotherapy. No difference was observed in OS.ConclusionsIn this study, different drug sensitivity was observed according to the type of KRAS mutation. NSCLC subpopulations with different KRAS mutation type should be considered as different subgroups and optimal chemotherapy regimens should be searched in further confirmative studies.

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer.

IntroductionThe utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC).ResultsKRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61–82.56) vs 56 months (95% CI: 68.71–127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93–59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17–0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14–1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations.Materials and MethodsWe retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations.ConclusionsKRASexon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Prognostic role of KRAS mutations in Sardinian patients with colorectal carcinoma

The presence of mutations in the KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor remains unclear. The aim of the present study was to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. A total of 551 patients with metastatic CRC at the time of enrolment were included. Clinical and pathological features of the disease, including follow-up information, were obtained from medical records and cancer registry data. For mutational analysis formalin-fixed paraffin-embedded tissue samples were processed using a standard protocol. The coding sequence and splice junctions of exons 2 and 3 of the KRAS gene were screened for mutations by direct automated sequencing. Overall, 186 KRAS mutations were detected in 183/551 (33%) patients: 125 (67%) were located in codon 12, 36 (19%) in codon 13, and 18 (10%) in codon 61. The remaining mutations (7; 4%) were detected in uncommonly-affected codons. No significant correlation between KRAS mutations and gender, age, anatomical location and stage of the disease at the time of diagnosis was identified. Furthermore, no prognostic value of KRAS mutations was found considering either TTM or OS. When patients were stratified by KRAS mutational status and gender, males were significantly associated with a longer TTM. The results of the present study indicate that KRAS mutation correlated with a slower metastatic progression in males with CRC from Sardinia, irrespective of the age at diagnosis and the codon of the mutation.

Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases.

While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown. A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses. Median patient age was 58 years (IQR, 50.4-66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597). KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. 2016;114:361-367. © 2016 Wiley Periodicals, Inc.