ObjectiveTo study value of long noncoding RNA H19 and HOTTIP in plasma in predicting efficacy of neoadjuvant chemotherapy (NAC) for resectable locally advanced gastric cancer. MethodsForty patients with T3–4aN+M0 gastric cancer and 40 patients with benign gastric diseases treated in the Yantai Yuhuangding Hospital Affiliated to Qingdao University from August 2020 to May 2021 were prospectively included. The expressions of H19 and HOTTIP in the plasma of gastric cancer and benign gastric diseases patients without any treatment after admission were detected before treatment (CAPEOX regimen was used in the patients with gastric cancer), then which were detected after 2 NAC courses for patients with gastric cancer. Meanwhile, some clinical items were detected and the efficacy of NAC was evaluated. The complete remission (CR) and partial remission (PR) were classified as objective remission, CR, PR, and disease stability were classified as disease control. The expressions of H19 and HOTTIP between the different patients were compared and the receiver operating characteristic (ROC) curve was used to evaluate their values in the diagnosis of resectable locally advanced gastric cancer. ResultsThere were 13 cases of T downstaging and 27 cases of T non-downstaging and 25 cases of objective remission and 35 disease control after NAC. The median relative expression levels of H19 and HOTTIP before NAC in the patients with gastric cancer were higher than those in the patients with benign gastric diseases (H19: 1.42 versus 0.98, Z=–3.835, P<0.001; HOTTIP: 2.15 versus 1.04, Z=–5.062, P<0.001), and which were in the patients with T downstaging and disease control were lower than those in the patients with T non-downstaging and 5 cases of disease progression (For T staging, H19: 1.12 versus 1.54, Z=–2.960, P=0.002; HOTTIP: 1.49 versus 2.30, Z=–2.310, P=0.019. For efficacy of NAC, H19: 1.39 versus 2.48, Z=–3.211, P<0.001; HOTTIP: 1.96 versus 3.25, Z=–2.393, P=0.014). The median relative expressions of H19 and HOTTIP after NAC were lower than those before NAC in the patients with gastric cancer (H19: 1.12 versus 1.42, Z=–3.965, P<0.001; HOTTIP: 1.30 versus 2.15, Z=–4.839, P<0.001). There were no significant differences in the changes of H19 and HOTTIP before and after NAC between the patients with T downstaging and T non-downstaging, and between disease control and disease progression (P>0.05). The areas of ROC curve of H19, HOTTIP, and combination of H19 and HOTTIP in diagnosis of resectable locally advanced gastric cancer were higher than 0.7. ConclusionsLncRNA H19 and HOTTIP might be potential tumor markers in gastric cancer, and their diagnostic values for resectable locally advanced gastric cancer are higher. Gastric cancer patients with low expressions of H19 and HOTTIP in plasma might be more sensitive to NAC.