Establishment Of High Efficient And Accurate Serological Diagnostic Methods For Malignant Tumor Of Hepatocellular Carcinoma By Luminex Combined Detection Technique

One out of seven of global deaths are caused by cancer according to research by IARC, and with increasing incidence and mortality, cancer has become the leading cause of death in China since 2010. About 782,500 new liver cancer cases and 745,500 liver cancer deaths were estimated to have occurred in 2012 worldwide, and half of them were occurred in China. That same year, about 1800,000 new lung cancer cases occurred worldwide. In 2015, studies reported that lung cancer was the most frequently diagnosed cancer and the leading cause of cancer death in China. Among them, HCC accounts for 70%-90% of liver cancer, NSCLC accounts for 80%-85% of lung cancer. Numerous studies have shown that early detection and diagnosis of HCC, NSCLC and other malignant tumors could significantly improve the prognosis and survival of the patients. However, due to the lack of effective screening strategies, most patients are diagnosed with HCC(>80%) or NSCLC(>65%) in advanced stage and have missed the best time of treatment, the 5-year survival rate of them is low. All these facts have caused enormous health and life damage to patients and brought heavy economic burden to family and society.Our study aimed to establish an efficient and accurate diagnostic system for HCCn NSCLC and other malignant tumors through using multiplex Luminex technology. In first part of our study about HCC, we used 9 markers to prepare multiplex Luminex kit,1200 serum samples with different diseases or healthy control were tested by this kit and the results were analyzed with single or combination of these markers. We found that CEACAM1 could be an independent serological diagnostic marker for HCC, which had high sensitivity and specificity. Combining CEACAM1 with AFP (the commonly serological diagnosis marker for liver cancer) and GP73 which had an effective diagnostic accuracy for HCC in report, the combo test could further improve the diagnostic accuracy of HCC, especially for early stage HCC. Interestingly, combination of CEACAM1 and GP73 had a good complementary diagnostic value for AFP-negative HCC patients. Combined with clinical data, we further showed that GP73 and CEACAM1 correlated well with AFP to indicate HCC progression and liver tissue damage. In addition, we also found that GP73 might be utilized as a general indicator for cancer screening combining with other markers. For example, by combining with DKK1 it could give better diagnostic accuracy for screening with colorectal carcinoma and esophageal carcinoma, and combining with HGF lead to better diagnosis for gastrointestinal carcinoma. In second part about lung cancer, we choose tumor-associated autoantibodies as biomarkers,93 serum samples from NSCLC patients or healthy controls were tested by a multiplex Luminex kit which could detect 23 tumor-associated autoantibodies at the same time. The results were analyzed with single or combined test of these markers. We found that each of seven autoantibodies (NY-ESO-1、p53、CDK、annexinA2、IMP1、ubiquilinl and PGAM1) had certain significance for the diagnosis of NSCLC and combination of seven autoantibodies could further enhance the diagnostic accuracy.Taken together, our study has established an efficient and accurate diagnostic system for HCC, NSCLC and other malignant tumors using multiplex Luminex technology, which can help the improvement of early diagnosis, early treatment and therapeutic efficacy evaluation of HCC and NSCLC, as well as for general screening of other cancers.