Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer

Abstract Background The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. Methods The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. Results By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. Conclusions CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.

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Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

10.21203/rs.3.rs-125323/v1 ◽

2020 ◽

Author(s):

Ran Wei ◽

Jichuan Quan ◽

Shuofeng Li ◽

Zhao Lu ◽

Xu Guan ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Cancer Stemness ◽

Poor Overall Survival ◽

Tissue Samples ◽

Cox Regression Analysis ◽

Rna Methylation ◽

M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

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Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.10.1901 ◽

1993 ◽

Vol 11 (10) ◽

pp. 1901-1905 ◽

Cited By ~ 27

Author(s):

A S Pappo ◽

W M Crist ◽

J Kuttesch ◽

S Rowe ◽

R A Ashmun ◽

...

Keyword(s):

Tumor Cell ◽

Dna Content ◽

Cox Regression ◽

Prognostic Significance ◽

Progression Free Survival ◽

Embryonal Rhabdomyosarcoma ◽

Clinical Group ◽

Anatomic Site ◽

Cox Regression Analysis ◽

Diploid Cells

PURPOSE The prognostic value of tumor-cell DNA content (ploidy) was evaluated in children with unresectable, nonmetastic rhabdomyosarcoma of embryonal histology. PATIENTS AND METHODS Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991. Tumors were classified as diploid or hyperdiploid (DNA content, 1.1 to 1.8 times that of normal diploid cells). The influence of ploidy on clinical outcome was assessed by the Kaplan-Meier technique and Cox regression analysis with stepwise selection. RESULTS Twelve of the tumor specimens were diploid and 22 were hyperdiploid. The patient groups defined by diploid or hyperdiploid tumors had similar presenting characteristics (eg, age, tumor size, and anatomic site). Significantly more children with hyperdiploid tumors achieved a complete response than did children with diploid tumors (85% v 42%; P = .01). The probability of progression-free survival at 5 years (+/- SE) was 91% +/- 6% for the hyperdiploid group, compared with 17% +/- 11% for the diploid group (P < .001). Hyperdiploidy was also associated with a significantly higher overall survival rate at 5 years: 96% +/- 4% versus 50% +/- 14% (P = .004). Ploidy retained its prognostic significance after adjustment for tumor site in the Cox regression model. CONCLUSION Tumor-cell ploidy strongly correlates with outcome in children with nonmetastic, unresectable embryonal rhabdomyosarcoma. The two biologically distinct groups identified by this measure would benefit from further refinements in risk-directed therapy.

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Identification of a Novel Glycolysis-Related Signature to Predict the Prognosis of Patients with Breast Cancer

10.21203/rs.3.rs-720991/v1 ◽

2021 ◽

Author(s):

Menglin He ◽

Cheng Hu ◽

Jian Deng ◽

Hui Ji ◽

Weiqian Tian

Keyword(s):

Breast Cancer ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Gene Signature ◽

High Risk Group ◽

Low Risk ◽

Cox Regression Analysis ◽

Expression Levels ◽

Incidence And Mortality

Abstract Background: Breast cancer (BC) is a kind of cancer with high incidence and mortality in female. Conventional clinical characteristics are far from accurate to predict individual outcomes. Therefore, we aimed to develop a novel signature to predict the survival of patients with BC. Methods: We analyzed the data of a training cohort from the TCGA database and a validation cohort from GEO database. After the applications of GSEA and Cox regression analyses, a glycolysis-related signature for predicting the survival of patients with BC was developed. The signature contains AK3, CACNA1H, IL13RA1, NUP43, PGK1, and SDC1. Then, we constructed a risk score formula to classify the patients into high and low-risk groups based on the expression levels of six-gene in patients. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to assess the predicted capacity of the model. Next, a nomogram was developed to predict the outcomes of patients with risk score and clinical features in 1, 3, and 5 years. We further used Human Protein Atlas (HPA) database to validate the expressions of the six biomarkers in tumor and sample tissues.Results: We constructed a six-gene signature to predict the outcomes of patients with BC. The patients in high-risk group showed poor prognosis than that in low-risk group. The AUC values were 0.719 and 0.702, showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that these biomarkers could independently predict the prognosis of BC patients without being affected by clinical factors. The expression levels of all six biomarkers in BC tissues were higher than that in normal tissues except AK3. Conclusion: We developed a six-gene signature to predict the prognosis of patients with BC. Our signature has been proved to have the ability to make an accurate and obvious prediction and might be used to expand the prediction methods in clinical.

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Prognostic significance of BRCA1, PARP1, and PARP2 in sporadic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22114 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22114-e22114 ◽

Cited By ~ 1

Author(s):

A. Gennari ◽

M. Sormani ◽

L. Varesco ◽

P. Pronzato ◽

V. Viassolo ◽

...

Keyword(s):

Breast Cancer ◽

Mrna Expression ◽

Sporadic Breast Cancer ◽

Cox Regression ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Prognostic Significance ◽

Breast Cancer Susceptibility Gene ◽

Cox Regression Analysis

e22114 Background: Breast cancer susceptibility gene (BRCA1) is a tumor suppressor gene whose mutation is associated with the development of hereditary breast cancer. In sporadic tumors, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, has been suggested to be associated with prognosis. Cells with BRCA1 loss of function are deficient in DNA double strand break repair thus activating poly(ADP-ribose) polymerases (PARPs) whose catalytic activity is immediately stimulated by DNA strand-breaks. The aim of this study was to evaluate the prognostic value of BRCA1 and PARPs (PARP1 and 2) in sporadic breast cancer. Methods: We merged two previously published Affymetrix gene expression datasets: GSE 1456 (159 patients, median follow up 7 years) and GSE 2494 (249 patients, median follow up 10 years). Microarray data preprocessing was carried out using Bioconductor software (gcrma procedure). Expression of BRCA1, PARP1 and PARP2 mRNA were evaluated as continuous variables. Kaplan Meier survival curves and Cox regression analysis (stratified by database) were used to assess the prognostic capability of the identified biomarkers. Results: High mRNA expression of BRCA1, PARP1 and PARP2 was correlated with an adverse prognosis. Relapse Free Survival (RFS) Hazard Ratio was 1.6 (95% CI, 1.2 to 2.1) for BRCA1 (p = 0.002), 1.7 (95% CI, 1.2 to 2.4) for PARP1 (p = 0.002) and 1.7 (95% CI, 1.3 to 2.3) for PARP2 (p = 0.001). By multivariate analysis all 3 genes resulted independently correlated with RFS. When interaction with systemic adjuvant therapy (107 patients treated) was tested, BRCA1 mRNA expression was strongly associated with treatment: HR 2.3 (95% CI, 1.4 to 3.7, p 0.001); p for interaction = 0.06. Conclusions: This study shows that BRCA1, PARP1 and PARP2 are all significantly associated with prognosis in sporadic breast cancer. No significant financial relationships to disclose.

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The prognostic value of baseline neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for predicting clinical outcome in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan (nal-IRI; MM-398) + 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15795 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15795-e15795 ◽

Cited By ~ 1

Author(s):

Andrea Wang-Gillam ◽

Li-Tzong Chen ◽

Chung-Pin Li ◽

Gyorgy Bodoky ◽

Andrew Dean ◽

...

Keyword(s):

Cox Regression ◽

Prognostic Significance ◽

Progression Free Survival ◽

Exploratory Analysis ◽

Ductal Adenocarcinoma ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Kaplan Meier ◽

Hazard Ratios ◽

Liposomal Irinotecan

e15795 Background: Increased NLR and PLR have been associated with poor survival in several malignancies. Here we report the association of NLR and PLR with overall survival (OS) and progression-free survival (PFS) in the NAPOLI-1 trial (NCT01494506), which evaluated nal-IRI+5-FU/LV for the treatment of mPDAC patients (pts) after disease progression following gemcitabine-based therapy. Methods: Pts missing baseline NLR/PLR data were excluded. Medians reflect Kaplan-Meier estimates; hazard ratios (HRs) reflect Cox regression analysis. P values in this exploratory analysis are descriptive. Results: Of 116 evaluable pts in the nal-IRI+5-FU/LV arm, 82 (71%) had NLR ≤5 and 44 (38%) had PLR ≤150 (data cutoff: Nov 16, 2015). Of 105 evaluable pts in the 5-FU/LV control arm, 73 (70%) had NLR ≤5 and 36 (34%) had PLR ≤150. In pts with baseline NLR ≤5 or PLR ≤150, median OS and PFS were significantly longer in the nal-IRI+5-FU/LV treatment arm vs the 5-FU/LV control arm (Table). In pts with baseline NLR >5 or PLR >150, median OS and PFS were numerically longer in the treatment vs control arm, but differences were less compelling (95% CIs for HRs included 1). Conclusions: Median OS and PFS were improved with nal-IRI+5-FU/LV vs 5-FU/LV in pts with baseline NLR ≤5 or PLR ≤150. This exploratory analysis extends the prognostic significance of NLR and PLR to the post-gemcitabine setting. Clinical trial information: NCT01494506. [Table: see text]

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Inflammatory prognostic markers in endometrial carcinoma: Systemic immune-inflammation index and prognostic nutritional index

Medical Science and Discovery ◽

10.36472/msd.v7i1.339 ◽

2020 ◽

Vol 7 (1) ◽

pp. 351-359 ◽

Cited By ~ 1

Author(s):

Cem Mirili ◽

Mehmet Bilici

Keyword(s):

Cox Regression ◽

Prognostic Significance ◽

Myometrial Invasion ◽

Prognostic Nutritional Index ◽

Progression Free Survival ◽

Roc Curve Analysis ◽

Clinicopathologic Characteristics ◽

Cox Regression Analysis ◽

Nutritional Index ◽

Immune Inflammation

Objective: Systemic inflammatory response markers have prognostic significance in many cancer types. Although the prognostic values of neutrophil/lymphocyte (NLR), and platelet/lymphocyte ratios (PLR) have been shown in patients with Endometrial Cancer (EC) there is no information in the literature about systemic immune-inflammation index (SII) and prognostic nutritional index (PNI). In our study, we aimed to reveal the prognostic role of SII and PNI in EC. Material and Methods: Medical data for 101 patients with EC were reviewed retrospectively. NLR, PLR, SII and PNI values were dichotomized based on receiver operating characteristic (ROC) curve analysis (cut-off values: 3.3; 177; 1035.9, and 38, respectively). At the time of diagnosis concentrations of these four serum inflammatory markers were analyzed to determine their potential association with clinicopathologic characteristics and to assess their prognostic values via the Kaplan-Meier method and multivariate Cox regression analysis. Results: Patients with higher NLR, PLR, SII, and lower PNI values had shorter progression-free survival (PFS) and overall survival (OS) times. Higher NLR, SII, and lower PNI, were associated with FIGO stages, lymph node involvement, lymphovascular invasion, and cervical stromal invasion while additionally NLR and PNI were associated with worse ECOG performance scores (2-3) and myometrial invasion. In univariate analyses, all these four variables were prognostic for both OS and PFS, whereas in multivariate analyzes only NLR, SII and PNI were found to be independent factors for OS and PFS. Conclusion: For the first time in the literature SII and PNI were determined to be independent prognostic factors for both OS and PFS in EC.

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IL-11RA is a Prognostic Biomarker and Correlated with Immune Infiltration in Lung Adenocarcinoma

10.21203/rs.3.rs-673757/v1 ◽

2021 ◽

Author(s):

Aitao Nai ◽

SHOAIB BASHIR ◽

Ling Jin ◽

Zirui He ◽

Shuwen Zeng ◽

...

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Cox Regression ◽

Progression Free Survival ◽

Clinicopathological Parameters ◽

Free Survival ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

Potential Biomarker

Abstract Background: Interleukin-11 receptor subunit alpha (IL-11RA) contributes to multiple biological processes in various tumors. However, the role of IL-11RA in Lung adenocarcinoma (LUAD) is still undetermined. The study aims to explore the role of IL-11RA in LUAD via an integrated bioinformatics analysis. Methods: TIMER, GEPIA, TCGA and HPA databases analysis were used to detect IL-11RA expression. UALCAN database was used to analysis the correlation between IL-11RA expression and clinicopathological parameters of LUAD. Kaplan-Meier Plotter, TCGA and GEO databases were used to analysis overall survival (OS) and progression-free survival (PFS) of the LUAD patients. Univariate Cox regression analysis was used to assess the prognostic value of IL-11RA in different clinical characteristics. GSEA, and TIMER were used to investigate the relationship between IL-11RA and immune infiltration.Results: The expression of IL-11RA was down-regulated in LUAD tissues. Furthermore, IL-11RA expression was closely associated with clinical stage, lymph node stage and smoking habits. The patients with lower IL-11RA expression had poorer overall survival (OS) and progression-free survival (PFS). Lower IL-11RA expression was significantly associated with its hypermethylation, and the hypermethylation of CpG site at cg14609668 and cg21504624 was obviously correlated with poorer OS. Then, we found that IL-11RA may play an important role in LUAD progression and immune regulations. Notably, High expression of IL-11RA may suppress the progression of LUAD through inhibiting cell proliferation and immune cell infiltration, especially in B cells, CD4+ T cells, and Dendritic Cell. Conclusions: Decreased IL-11RA expression correlates with poor prognosis and immune infiltration in LUAD. Our work highlights IL-11RA might be a potential biomarker for prognosis and provide a new therapeutic target for LUAD patients.

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Prognostic value of the albumin–globulin ratio and albumin–globulin score in patients with multiple myeloma

Journal of International Medical Research ◽

10.1177/0300060521997736 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199773

Author(s):

Ying Cai ◽

Yu Zhao ◽

Qiuxin Dai ◽

Maozhong Xu ◽

Xin Xu ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Prognostic Value ◽

Cox Regression ◽

Characteristic Curve ◽

Prognostic Significance ◽

Progression Free Survival ◽

Free Survival ◽

Cox Regression Analysis ◽

Kaplan Meier

Objective The albumin–globulin ratio (AGR) has been identified as a promising prognostic predictor of mortality in patients with hematological malignancies. This study investigated the prognostic significance of AGR in patients with multiple myeloma. Methods Two hundred patients diagnosed with multiple myeloma from January 2010 to October 2018 were retrospectively analyzed and followed up until December 2019. Kaplan–Meier curves and multivariate Cox regression analysis were applied to detect the prognostic value of AGR. Results The median follow-up period was 36 months. The optimal cutoff of AGR was 1.16 according to receiver operating characteristic curve analysis. High AGR was significantly correlated with better overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that low AGR was an independent prognostic factor for worse OS (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.15–2.94) and PFS (HR = 1.53, 95% CI = 1.09–2.17). Conclusions AGR may represent a potential prognostic biomarker in patients with multiple myeloma. Mini Abstract: We demonstrated that high AGR was associated with a favorable overall survival and progression-free survival in patients with multiple myeloma.

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Association of Perioperative Cell-free DNA (cfDNA) Concentrations with Risk of Recurrence in Patients with Breast Cancer

10.21203/rs.3.rs-1017958/v1 ◽

2021 ◽

Author(s):

Fara Hassan ◽

Jiang Huai Wang ◽

Carolyn Cullinane ◽

Michael Ita ◽

Mark Corrigan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cox Regression ◽

Perioperative Period ◽

Breast Cancer Patients ◽

Cell Free Dna ◽

Cox Regression Analysis ◽

Free Dna ◽

Post Operative Period ◽

Potential Biomarker

Abstract Background: Circulating cell-free DNA (cfDNA) is a potential biomarker of disease status in cancer patients and provides valuable diagnostic and prognostic information in breast cancer. In this study, we sought to quantify the cfDNA concentrations in the perioperative period and to investigate its prognostic relevance in breast cancer patients.Methods: Sixty-three (n=63) breast cancer patients undergoing curative surgery were screened for inclusion. Blood samples were collected: pre-operatively (Pre-op), post-operatively (POD) within weeks 1-2, weeks 3-4 and weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. All patients were followed up for 5 years.Results: The median age was 52(26-84) years. During the perioperative period, patients with high cfDNA concentrations(cutoff:480ng/ml) had inferior recurrence free survival (RFS) than those with lower cfDNA concentrations (pre-operative period: median RFS: 30(3-60) months versus 60(6-60) months (p<0.0001), post-operative period: median RFS: 24(3-60) months versus 60(6-60) months (p<0.0001). Multivariate Cox regression analysis showed that post op cfDNA concentration (p=0.017), subtypes (p=0.011) and tumour size (p=0.006) were negative prognostic factor for RFS in the pre-operative period and post-operative period.Conclusion: Our study demonstrated the prognostic ability of perioperative cfDNA concentrations in breast cancer patients. Further, prospective studies are warranted to validate its clinical utility in breast cancer.

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Variations in Y chromosome-related genes and clinical outcome in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.634 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 634-634 ◽

Cited By ~ 1

Author(s):

Stefan Stremitzer ◽

Sebastian Stintzing ◽

Volker Heinemann ◽

Wu Zhang ◽

Dongyun Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Outcome ◽

Metastatic Colorectal Cancer ◽

Y Chromosome ◽

Cox Regression ◽

Progression Free Survival ◽

Nucleotide Polymorphisms ◽

Tissue Samples ◽

Exon 2 ◽

Cox Regression Analysis

634 Background: Males have a higher cancer risk and worse clinical outcome in metastatic colorectal cancer compared to females, which has been related to loss of Y chromosome. In this study, we investigated single nucleotide polymorphisms (SNPs) in Y chromosome-related genes and their association with clinical outcome in patients from the FIRE-3 study (NCT00433927). Methods: Three SNPs (FOXL2 rs11924939 C>T, DMRT1 rs755383 T>C and DMRT1 rs3739583 A>T) were investigated in genomic DNA isolated from tissue samples of 295 patients (KRAS exon 2 wild-type) from the bevacizumab-arm of the FIRE-3 study. The median age of 195 (66.6%) male and 98 (33.4%) female patients was 65 months (range 27-76). Seventy-four (25.6%) patients had right-sided tumors and 215 (74.4%) had left-sided tumors. Results: The C/C genotype of DMRT1 rs755383 T>C was associated with significantly longer progression-free survival (PFS) in univariable (C/C 14.3 months, T/T or T/C 10.0 months, hazard ratio (HR) 0.58; P=0.033) and in multivariable Cox regression analysis adjusted for baseline characteristics (HR 0.63; P=0.026). This difference was confirmed in male patients (C/C 15.9 months, T/T or T/C 10.1 months, HR 0.58; P=0.038 and HR 0.53; P=0.023) and patients with left-sided tumors (C/C 14.6 months, T/T or T/C 10.4 months, univariable HR 0.61; P=0.044 and multivariable HR 0.60; P=0.046). The T/T genotype of FOXL2rs11924939 C>T was associated with longer PFS in patients with right-sided tumors (T/T 13.4 months, C/C or C/T 7.8 months, univariable HR 0.47; P=0.043 and multivariable HR 0.30; P=0.031) and shorter PFS in left-sided tumors (T/T 6.9 months, C/C or C/T 11.3 months, univariable HR 1.83; P=0.017 and multivariable HR 1.99; P=0.009). Conclusions: In this study, we demonstrated for the first time that SNPs in Y chromosome-related genes are associated with outcome in metastatic colorectal cancer in a gender- and location-specific way. These results highlight the value of the SNPs as potential biomarkers.

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