A Prospective Study Of Immune-related Cytokines Prediction Of Chemotherapy Efficacy And Survival In Gastric Cancer Patients

Background: The immune system of patients plays an important role in theoccurrence and development of gastric cancer. We aimed to detect protein and mRNAlevels of immune factors in peripheral blood, analyze the relationship between theimmune status and clinicopathological features of gastric cancer patients, observetrends of immune status during chemotherapy, determine the affect of immune statuson efficacy and prognosis, and look for the immune markers to predictchemotherapy efficacy, recurrence and prognosis.Method: Part1, we detected protein and mRNA levels of IL-2, IL-6, TGF-β,HIF-1α, PD-1, PD-L1, CTLA-4in peripheral blood of gastric cancer patients fromJan2013to Jan2014by ELISA and RT-PCR method and analyzed the relationshipbetween immune status and clinicopathological features of patients; Part2, aprospective study design was to detect the expression levels and change trends ofthese immune factors in the course of adjuvant chemotherapy; Part3, detection theexpression levels and change trends of these immune factors in the course of first-linetreatment process to analyzed the relationship between immune status and curativeeffect and prognosis.Results:1. A total of116GC patients were enrolled. IL-2, PDL-1proteincontent was lower than healthy group (P<0.01), but CTLA-4was higher (P<0.01);HIF-1α, PD-1mRNA level was higher than healthy group (P<0.01), but PD-L1waslower (P<0.01). Immune factors were positively correlated in healthy group (R>0.60,P<0.01), and each factor was closed between protein and mRNA(R>0.90, P<0.01). InGC patients, each immune factor was positively correlated at protein level (R>0.40,P<0.01), IL-2, IL-6, TGF-β, PD-1, PDL-1, CTLA-4were positively correlated atmRNA level (P<0.01), but HIF-1α was negatively correlated with TGF-β,PDL-1(P<0.05). IL-2, IL-6, TGF-β, PDL-1, PD-1, CTLA-4protein levels and mRNAlevels were positively correlated in GC patients (R>0.50, P<0.01), but HIF-1α wasnegative(R=-0.49, P<0.01). 2. IL-6, TGF-β, HIF-1α, CTLA-4, PD-1protein levels in men were lower thanwomen patients (P <0.05), IL-6, TGF-β, HIF-1α, PDL-1protein in GC patients werelower than those without liver metastasis (P <0.05). The mRNA expression of HIF-1αin male patients was lower than female (P <0.01), and HIF-1α, PD-1was lower inpatients with liver metastasis(P<0.05).3. The change trend of immune factors in adjuvant chemotherapy showed thatIL-2, IL-6, TGF-β, HIF-1α, PD-1, PD-L1proteins were ascent-decline, CTLA-4wasserrated trend and mRNA levels were lagged in protein levels.4. The protein levels of these immune factors in chemotherapy showed a trend ofascent-decline in patients with advanced gastric cancer, and mRNA levels showed lagin protein levels.5. IL-2, IL-6, TGF-β, PDL-1, CTLA-4protein levels were higher in advancedGC patients who achieved PR than PD with PD, HIF-1α, PD-1was lower. mRNAdetection showed that IL-2, IL-6, TGF-β, PD-1in PR patients is higher than PDpatients, HIF-1α, PDL-1, CTLA-4was less than PD patients (P>0.05).6. The change magnitude of these immune factors in patients achieved PR andSD is larger than patients achieved PD in the first-line chemotherapy.Conclusion:1. Immune function between individuals was independent anddifferent in both healthy people and GC patients, but immune factors were closelyrelated and consistent change in each person.2. GC patients showed immunesuppression, female patients showed stronger immune response than male in thedevelopment of gastric cancer, and immune function in patients with liver metastasessignificantly decreased.3. Combined immune therapy early may improve immunefunction during the adjuvant chemotherapy.4. High protein levels of IL-2, IL-6,TGF-β, PDL-1may lead to better efficacy of chemotherapy in advanced GC cancer,and immune factors changed larger may correlated to better efficacy.