| Objective: Lung cancer is a kind of malignant tumor with the highest morbidity and mortality in the world.Most patients with lung cancer are diagnosed at an advanced stage.Chemotherapy is still the most commonly used treatment for patients with advanced lung cancer.At present,monitoring the efficacy of chemotherapy for advanced lung cancer mostly depends on the response evaluation criteria in solid tumors(RECIST)based on imaging.However,tumor progression is often not comprehensively detected by imaging in daily clinical practice.For example,conditions caused by central lung cancer such as atelectasis,pericardial effusion or pleural effusion,lymphatic invasion,and pleural lung cancer are difficult to be detected early by imaging,and imaging studies are often lagging and have radiation hazards.Therefore,there is a need to integrate effective serum markers for the assessment of the efficacy of lung cancer chemotherapy.In the early stage of tumorigenesis,the body’s immune system can recognize a small number of abnormal proteins on the surface of tumor cells,namely tumor-associated antigens(TAAs),and produce auto-antibodies against these antigens.The mutation of tumor suppressor gene P53(P53)is the most common genetic change in human cancer,which can lead to the expression of mutant p53 proteins.Those proteins accumulate in cancer cells and can induce the production of p53 antibodies in cancer patients.Protein gene product 9.5(PGP9.5)is a member of the ubiquitin c-terminal hydrolase(UCH)family expressed in neural tissues,which regulates many cellular processes including cell cycle progression and cell death.SRY-box containing gene 2(SOX2)has been confirmed as a lung squamous cell carcinoma oncogene and is a transcription factor expressed in various types of embryonic and adult stem cells.G antigen 7(GAGE7),ATP binds to RNA helicase(GBU4-5),melanoma antigen A1(MAGEA1),and human cancer antigen(CAGE)all belong to tumor/testis antigens(CTAs),which are not expressed in normal tissues and only expressed in malignant and testicular tissues.And CTAs can promote epithelial-mesenchymal transition(EMT)and the development of cancer stem-like cells and accelerate the development,invasion,and metastasis of tumors.Therefore,in this study,we compared the expression levels(U/ml)of seven auto-antibodies of P53,SOX2,PGP9.5,MAGE A1,CAGE,GBU4-5,and GAGE7 in patients with advanced lung cancer before and after first-line chemotherapy,in order to assess the value of seven auto-antibodies in the evaluation of the effect of lung cancer chemotherapy and the significance of differentiating different pathological types of lung cancer.Methods: Forty-nine patients with advanced lung cancer(IIIB ～ IV)diagnosed by histopathology who were hospitalized in the Department of Respiratory Medicine of the Affiliated Hospital of Guilin Medical University from June 2019 to January 2020 were finally included as the study subjects.Seven auto-antibody levels of lung cancer were measured before and after 4 cycles of standardized chemotherapy.Thoracic CT,brain and abdominal computed tomography(CT),bone scan and blood biochemical analysis were completed according to the guidelines for the diagnosis and treatment of lung cancer before chemotherapy.Chest CT was completed after 4 cycles of chemotherapy for image-based efficacy evaluation of solid tumors.Eighteen of the 49 patients had concomitant radiotherapy or targeted therapy during chemotherapy or were lost to follow-up,and the patients were finally divided into two groups for statistical analysis.(1)Preliminarily analyzed the differences of seven auto-antibodies in lung cancer among different pathological types in 49 patients with advanced lung cancer.(2)Finally excluded 18 patients with advanced lung cancer who were treated with radiotherapy or targeted therapy or lost to follow-up during chemotherapy,and included 31 patients with advanced lung cancer who completed 4 cycles of chemotherapy(during which radiotherapy,targeted therapy and immunotherapy were not performed except chemotherapy).Chest CT examination was performed after 4 cycles of standard chemotherapy.Blood samples were drawn within 10 days after chemotherapy for the detection of seven auto-antibodies in lung cancer.The differences in the expression levels of seven auto-antibodies in lung cancer before and after the first-line chemotherapy regimen were compared to understand its value in the evaluation of chemotherapy effect in advanced lung cancer.Results: analysis of the differences in the expression of the seven auto-antibodies of lung cancer in different pathological types of lung cancer:(1)the expression levels of PGP9.5,GAGE7 and MAGEA1 in the lung adenocarcinoma and lung squamous cell carcinoma groups(U/ml)were higher than those in the small cell lung cancer group(P<0.05).(2)there was no statistically significant difference in the expression levels of the seven auto-antibodies in lung cancer between lung adenocarcinoma and lung squamous cell carcinoma(P > 0.05).(3)the expression levels of P53,SOX2,gbu4-5 and CAGE in the lung adenocarcinoma,lung squamous cell carcinoma and small cell lung cancer groups were not statistically significant(P > 0.05).Comparison and analysis of the expression levels of seven auto-antibodies of lung cancer before and after 4 cycles of chemotherapy for advanced lung cancer :(1)the response rates of p53 and CAGE after chemotherapy in PR(n = 12)and SD+PD(n=19)groups were statistically significant(P<0.05).(2)in the PR group,the expression levels of p53,gbu4-5 and CAGE after 4 cycles of chemotherapy(U/ml)were lower than those before chemotherapy,and the difference was statistically significant(P <0.05).(3)in the SD+PD group,there was no significant change in the expression levels of the seven auto-antibodies of lung cancer before and after chemotherapy,and the difference was not statistically significant(P >0.05).Conclusions:1.PGP9.5,GAGE7 and MAGE A1 may be used to differentiate non-small cell lung cancer from small cell lung cancer.2.P53 and CAGE may have some auxiliary value for image-based efficacy evaluation.3.P53,GBU4-5,and CAGE may have potential value as assessment indicators of the effect of chemotherapy in advanced lung cancer.4.Seven auto-antibodies to lung cancer may be of little value in monitoring the condition of patients who do not respond to chemotherapy. |
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