Abstract 2525: A novel splicing factor, SPF45/RBM17, might influence 5-FU resistance of gastric carcinoma
Authors: Koji Maruo, Masakazu Yashiro, Takashi Sakuma, Gen Tsujio, Yasuhiro Fukui, Hiroaki Kasashima, Kiyoshi Maeda
Journal: Cancer Research (2024)

Abstract Background: SPF45/RBM17 was identified as a factor required for splicing of short introns in mRNA precursors transcribed from DNA. SPF45 is also thought to be related to anti-cancer drug resistance, suggesting that the SPF45 molecule has a different resistance mechanism from the conventional mechanism of anticancer drug resistance. In this study, we investigated the relationship between SPF45 expression and anticancer drug sensitivity in gastric cancer. Materials and Methods: A total of 654 gastric cancer cases were used in this study. SPF45 expression was examined using immunohistochemistry. The correlation between SPF45 expression and clinicopathological factors was evaluated. Results: Of the 654 gastric cancer cases, 240 were positive for SPF45 expression and 414 were negative for expression. There was no significant difference in age and gender between the two groups, but SPF45-positive cases were significantly more frequent in patients with undifferentiation (p = 0.004), lymphatic invasion (p = 0.013) and venous invasion (p &amp;lt; 0.001). As for anticancer drug therapy, 215 of the 654 patients with gastric cancer who underwent radical surgery were treated with adjuvant chemotherapy and 94 patients with advanced recurrent gastric cancer were treated with chemotherapy. 75 SPF45-positive-patients who received 5FU-based adjuvant chemotherapy (S-1, UFT, 5-DFUR) after surgery had significantly worse recurrence-free survival (RFS) than 140 SPF45-negative-patients (p=0.027). 102 SPF45-positive-patients who didn’t receive adjuvant chemotherapy was no significantly different in RFS from 203 SPF45-negative-patients. In the 215 patients who received adjuvant chemotherapy, 81 DPD-positive patients had significantly worse RFS than DPD-negative patients (p=0.043). In the 305 patients who didn’t receive adjuvant chemotherapy, there was no significant difference in RFS between DPD-positive patients and DPD-negative patients (p=0.880). SPF45-positive cases were significantly more frequent in patients with DPD expression (p &amp;lt; 0.001).In 94 patients with advanced recurrent gastric cancer treated with chemotherapy, there were 42 recurrent patients and 52 stage IV patients. 50 of SPF45-positive patients had significantly worse progression-free survival than 44 of SPF45-negative patients (p &amp;lt; 0.001). Regarding overall response, SPF45-positive-patients had worse response rate than SPF45-negative-patients (p=0.016). In SPF45 positive group, 20.0% responded (CR in 0% and PR in 20%) and 80.0% did not respond (SD in 52% and PD in 28%). In SPF45 negative group, 42.6% responded (CR in 0% and PR in 42.6%) and 57.4% did not respond (SD in 46.8% and PD in 10.6%) Conclusion: Our results suggest that the splicing factor SPF45 influences anticancer drugs such as 5-FU resistance in gastric cancer. Acknowledgments: We thank Kazuhiro Fukumura and Akila Mayeda, Fujita Health University. Citation Format: Koji Maruo, Masakazu Yashiro, Takashi Sakuma, Gen Tsujio, Yasuhiro Fukui, Hiroaki Kasashima, Kiyoshi Maeda. A novel splicing factor, SPF45/RBM17, might influence 5-FU resistance of gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2525.