Fisher linear discriminant analysis for classification and prediction of genomic susceptibility to stomach and colorectal cancers based on six STR loci in a northern Chinese Han population.

Shuhong Hao,Yujie Sui,Ming Ren,Gaoyang Chen,Qiwei Yang,Qingyu Wang,Dong Li,Zhaoyan Li

doi:10.7717/peerj.7004

Abstract

ObjectiveGastrointestinal cancer is the leading cause of cancer-related death worldwide. The aim of this study was to verify whether the genotype of six short tandem repeat (STR) loci including AR, Bat-25, D5S346, ER1, ER2, and FGA is associated with the risk of gastric cancer (GC) and colorectal cancer (CRC) and to develop a model that allows early diagnosis and prediction of inherited genomic susceptibility to GC and CRC.MethodsAlleles of six STR loci were determined using the peripheral blood of six colon cancer patients, five rectal cancer patients, eight GC patients, and 30 healthy controls. Fisher linear discriminant analysis (FDA) was used to establish the discriminant formula to distinguish GC and CRC patients from healthy controls. Leave-one-out cross validation and receiver operating characteristic (ROC) curves were used to validate the accuracy of the formula. The relationship between the STR status and immunohistochemical (IHC) and tumor markers was analyzed using multiple correspondence analysis.ResultsD5S346 was confirmed as a GC- and CRC-related STR locus. For the first time, we established a discriminant formula on the basis of the six STR loci, which was used to estimate the risk coefficient of suffering from GC and CRC. The model was statistically significant (Wilks’ lambda = 0.471, χ2 = 30.488, df = 13, and p = 0.004). The results of leave-one-out cross validation showed that the sensitivity of the formula was 73.7% and the specificity was 76.7%. The area under the ROC curve (AUC) was 0.926, with a sensitivity of 73.7% and a specificity of 93.3%. The STR status was shown to have a certain relationship with the expression of some IHC markers and the level of some tumor markers.ConclusionsThe results of this study complement clinical diagnostic criteria and present markers for early prediction of GC and CRC. This approach will aid in improving risk awareness of susceptible individuals and contribute to reducing the incidence of GC and CRC by prevention and early detection.

Highlights

Gastrointestinal cancer is a leading cause of cancer-related death worldwide (Zhou et al, 2017)
By comparing the copy number of each short tandem repeat (STR) locus between gastric cancer (GC) and colorectal cancer (CRC) patients and healthy subjects, we found that the copy number of Androgen receptor (AR)-L was lower in GC and CRC patients than in healthy subjects (26.16 ± 2.91 vs. 27.80 ± 2.17, p = 0.032); the copy number of D5S346-S was higher in GC and CRC patients than in healthy subjects (14.84 ± 2.66 vs. 13.23 ± 1.45, p = 0.027); the copy number of D5S346-L was higher in GC and CRC patients than in healthy subjects (18.79 ± 4.21 vs. 15.50 ± 3.95, p = 0.009); and the copy number of ER2-L was lower in GC and CRC patients than in healthy subjects (19.74 ± 2.77 vs. 21.30 ± 2.19, p = 0.037)
There was no significant difference in the copy number of other STR loci between the GC and CRC patients and healthy subjects (p > 0.05)

Summary

Introduction

Gastrointestinal cancer is a leading cause of cancer-related death worldwide (Zhou et al, 2017). Of all types of gastrointestinal cancer, colorectal cancer (CRC) is the most common; CRC is the third most commonly diagnosed cancer in the United States and the fourth in China (Du et al, 2017; Siegel et al, 2017). The survival rate declines to 71% and 14% for patients diagnosed with regional and distant metastasis, respectively (Siegel et al, 2017). The incidence of gastric cancer (GC) is not as high as that of CRC in the United States, GC is the second most common malignancy in China (Zheng et al, 2019). GC is the second most common cause of cancer-related death worldwide (Torre et al, 2015). A deeper understanding of the molecular mechanisms in GC and CRC progression and the identification of early diagnostic biomarkers and predictive signals for the diseases have become urgent issues

Results

Discussion

Conclusion