nach oben

Cancer Chemotherapy and Pharmacology

Erschienen in:

20.04.2020 | Original Article

The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study

verfasst von: Jinsong Su, Baiyun Dai, Weitang Yuan, Guixian Wang, Zhiyong Zhang, Zhen Li, Jinbo Liu, Junmin Song

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

This study investigated the influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer (CRC) patients who received capecitabine-based adjuvant chemotherapy in real world.

Methods

A total of 315 CRC patients underwent R0 surgical resection and received capecitabine-based adjuvant chemotherapy were included. Clinical characteristics were collected from the hospital record system, prognosis was obtained by telephone follow-up. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of CRC patients were performed for the genotyping of polymorphism and mRNA expression of PD-L1, respectively. Analysis on the association between genotypes and prognosis was conducted.

Results

The median disease-free survival (DFS) of the 315 CRC patients was 5.1 years, the median overall survival (OS) was 6.0 years. Regarding the PD-L1 gene polymorphism analysis, the prevalence of 901T>C among the CRC patients was as follows: TT genotype 221 cases (70.16%), TC genotype 86 cases (27.30%), CC genotype 8 cases (2.54%), the minor allele frequency was 0.16, the distribution of three genotypes was in accordance with Hardy–Weinberg equilibrium (P = 0.915). Moreover, the prognosis analysis indicated that the median DFS of patients with TT and TC/CC genotype was 5.4 and 4.0 years, respectively (P = 0.008). The median OS of patients with the two genotypes was 6.4 and 5.0 years (P = 0.007). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for DFS (odds ratio = 1.56, P = 0.018). Furthermore, the mRNA expression results indicated that the mRNA expression of PD-L1 in PBMC of the patients with TC/CC genotype was significantly higher than patients with TT genotype (P < 0.001).

Conclusion

The prognosis of R0 resection CRC patients received capecitabine-based adjuvant chemotherapy in real world may be influenced by PD-L1 901T>C polymorphism through mediation of the mRNA expression of PD-L1.

Nur mit Berechtigung zugänglich

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492 CrossRefPubMed

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132. https://doi.org/10.3322/caac.21338 CrossRefPubMed

Abakushina EV, Gelm YV, Pasova IA, Bazhin AV (2019) Immunotherapeutic approaches for the treatment of colorectal cancer. Biochemistry (Mosc) 84(7):720–728. https://doi.org/10.1134/s0006297919070046 CrossRef

Emambux S, Tachon G, Junca A, Tougeron D (2018) Results and challenges of immune checkpoint inhibitors in colorectal cancer. Expert Opin Biol Ther 18(5):561–573. https://doi.org/10.1080/14712598.2018.1445222 CrossRefPubMed

Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T (2018) Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med 378(13):1177–1188. https://doi.org/10.1056/NEJMoa1713709 CrossRefPubMedPubMedCentral

McQuade RM, Stojanovska V, Bornstein JC, Nurgali K (2017) Colorectal cancer chemotherapy: the evolution of treatment and new approaches. Curr Med Chem 24(15):1537–1557. https://doi.org/10.2174/0929867324666170111152436 CrossRefPubMed

Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26(12):2006–2012. https://doi.org/10.1200/jco.2007.14.9898 CrossRefPubMed

Reck M, Brahmer J, Bennett B, Taylor F, Penrod JR, DeRosa M, Dastani H, Spigel DR, Gralla RJ (2018) Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Eur J Cancer 102:23–30. https://doi.org/10.1016/j.ejca.2018.05.005 CrossRefPubMed

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM (2018) Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 379(21):2040–2051. https://doi.org/10.1056/NEJMoa1810865 CrossRefPubMed

10.

Wu Y, Chen W, Xu ZP, Gu W (2019) PD-L1 distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol 10:2022. https://doi.org/10.3389/fimmu.2019.02022 CrossRefPubMedPubMedCentral

11.

Kim J, Cho J, Lee MH, Lim JH (2018) Relative efficacy of checkpoint inhibitors for advanced NSCLC according to programmed death-ligand-1 expression: a systematic review and network meta-analysis. Sci Rep 8(1):11738. https://doi.org/10.1038/s41598-018-30277-0 CrossRefPubMedPubMedCentral

12.

Ma LJ, Feng FL, Dong LQ, Zhang Z, Duan M, Liu LZ, Shi JY, Yang LX, Wang ZC, Zhang S, Ding ZB, Ke AW, Cao Y, Zhang XM, Zhou J, Fan J, Wang XY, Gao Q (2018) Clinical significance of PD-1/PD-Ls gene amplification and overexpression in patients with hepatocellular carcinoma. Theranostics 8(20):5690–5702. https://doi.org/10.7150/thno.28742 CrossRefPubMedPubMedCentral

13.

Han K, Zhang Y (2019) mRNA expression of programmed cell death ligand 1 and components of the phosphatidylinositol 3-kinase/AKT/phosphatase and tensin homolog pathway in epidermal growth factor receptor mutation-positive lung adenocarcinoma. J Cancer Res Ther 15(4):914–920. https://doi.org/10.4103/jcrt.JCRT_636_18 CrossRefPubMed

14.

Xie Q, Chen Z, Xia L, Zhao Q, Yu H, Yang Z (2018) Correlations of PD-L1 gene polymorphisms with susceptibility and prognosis in hepatocellular carcinoma in a Chinese Han population. Gene 674:188–194. https://doi.org/10.1016/j.gene.2018.06.069 CrossRefPubMed

15.

Krawczyk P, Grenda A, Wojas-Krawczyk K, Nicos M, Kucharczyk T, Jarosz B, Reszka K, Pankowski J, Krukowska K, Bozyk A, Szumilo J, Sawicki M, Trojanowski T, Milanowski J (2019) PD-L1 gene copy number and promoter polymorphisms regulate PD-L1 expression in tumor cells of non-small cell lung cancer patients. Cancer Genet 237:10–18. https://doi.org/10.1016/j.cancergen.2019.06.001 CrossRefPubMed

16.

Ntavatzikos A, Spathis A, Patapis P, Machairas N, Vourli G, Peros G, Papadopoulos I, Panayiotides I, Koumarianou A (2019) TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer. World J Gastrointest Oncol 11(7):551–566. https://doi.org/10.4251/wjgo.v11.i7.551 CrossRefPubMedPubMedCentral

17.

Mizushima T, Ikeda M, Kato T, Ikeda A, Nishimura J, Hata T, Matsuda C, Satoh T, Mori M, Doki Y (2019) Postoperative XELOX therapy for patients with curatively resected high-risk stage II and stage III rectal cancer without preoperative chemoradiation: a prospective, multicenter, open-label, single-arm phase II study. BMC Cancer 19(1):929. https://doi.org/10.1186/s12885-019-6122-2 CrossRefPubMedPubMedCentral

18.

Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zou J, Zhu X, Xu B (2019) Pyrotinib or lapatinib combined with capecitabine in HER2-positive metastatic breast cancer with prior taxanes, anthracyclines, and/or trastuzumab: a randomized phase II study. J Clin Oncol. https://doi.org/10.1200/jco.19.00108 CrossRefPubMedPubMedCentral

19.

Sasaki M, Miyoshi N, Fujino S, Ishikawa S, Saso K, Takahashi H, Haraguchi N, Hata T, Matsuda C, Mizushima T, Doki Y, Mori M (2019) Development of novel prognostic prediction models including the prognostic nutritional index for patients with colorectal cancer after curative resection. J Anus Rectum Colon 3(3):106–115. https://doi.org/10.23922/jarc.2018-041 CrossRefPubMedPubMedCentral

20.

Vacante M, Borzi AM, Basile F, Biondi A (2018) Biomarkers in colorectal cancer: current clinical utility and future perspectives. World J Clin Cases 6(15):869–881. https://doi.org/10.12998/wjcc.v6.i15.869 CrossRefPubMedPubMedCentral

21.

Yousef AM, Zawiah M, Al-Yacoub S, Kadi T, Tantawi DA, Al-Ramadhani H (2018) The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer. Cancer Chemother Pharmacol 82(2):237–243. https://doi.org/10.1007/s00280-018-3608-6 CrossRefPubMed

22.

Castro-Rojas CA, Esparza-Mota AR, Hernandez-Cabrera F, Romero-Diaz VJ, Gonzalez-Guerrero JF, Maldonado-Garza H, Garcia-Gonzalez IS, Buenaventura-Cisneros S, Sanchez-Lopez JY, Ortiz-Lopez R, Camacho-Morales A, Barboza-Quintana O, Rojas-Martinez A (2017) Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer. Drug Metab Pers Ther 32(4):209–218. https://doi.org/10.1515/dmpt-2017-0028 CrossRefPubMed

23.

Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG (2015) Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the NO16968 randomized controlled phase III trial. J Clin Oncol 33(32):3733–3740. https://doi.org/10.1200/jco.2015.60.9107 CrossRefPubMed

24.

Li S, Zhu L, Cheng X, Wang Q, Feng J, Zhou J (2019) The significance of CO₂ combining power in predicting prognosis of patients with stage II and III colorectal cancer. Biomark Med 13(13):1071–1080. https://doi.org/10.2217/bmm-2018-0321 CrossRefPubMed

25.

Sun DC, Shi Y, Wang YR, Lv Y, Yan H, Mao H, Wang ZK, Wu ZY, Shi WW, Dai GH (2017) KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients. Sci Rep 7(1):14368. https://doi.org/10.1038/s41598-017-14669-2 CrossRefPubMedPubMedCentral

26.

Kim SK, Kim SY, Kim CW, Roh SA, Ha YJ, Lee JL, Heo H, Cho DH, Lee JS, Kim YS, Kim JC (2019) A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer. Exp Mol Med 51(10):115. https://doi.org/10.1038/s12276-019-0319-y CrossRefPubMedCentral

27.

Ji D, Qiao M, Yao Y, Li M, Chen H, Dong Q, Jia J, Cui X, Li Z, Xia J, Gu J (2018) Serum-based microRNA signature predicts relapse and therapeutic outcome of adjuvant chemotherapy in colorectal cancer patients. EBioMedicine 35:189–197. https://doi.org/10.1016/j.ebiom.2018.08.042 CrossRefPubMedPubMedCentral

28.

Tao Y, Ding L, Yang GG, Qiu JM, Wang D, Wang H, Fu C (2018) Predictive impact of the inflammation-based indices in colorectal cancer patients with adjuvant chemotherapy. Cancer Med. https://doi.org/10.1002/cam4.1542 CrossRefPubMedPubMedCentral

29.

Catalano C, da Silva Filho MI, Frank C, Jiraskova K, Vymetalkova V, Levy M, Liska V, Vycital O, Naccarati A, Vodickova L, Hemminki K, Vodicka P, Weber ANR, Forsti A (2018) Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer. PLoS ONE 13(2):e0192385. https://doi.org/10.1371/journal.pone.0192385 CrossRefPubMedPubMedCentral

30.

Wu Y, Zhao T, Jia Z, Cao D, Cao X, Pan Y, Zhao D, Zhang B, Jiang J (2019) Polymorphism of the programmed death-ligand 1 gene is associated with its protein expression and prognosis in gastric cancer. J Gastroenterol Hepatol 34(7):1201–1207. https://doi.org/10.1111/jgh.14520 CrossRefPubMed

31.

Du W, Zhu J, Chen Y, Zeng Y, Shen D, Zhang N, Ning W, Liu Z, Huang JA (2017) Variant SNPs at the microRNA complementary site in the B7H1 3'untranslated region increase the risk of nonsmall cell lung cancer. Mol Med Rep 16(3):2682–2690. https://doi.org/10.3892/mmr.2017.6902 CrossRefPubMedPubMedCentral

32.

Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E (2008) Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 26(21):3523–3529. https://doi.org/10.1200/jco.2007.15.4138 CrossRefPubMed

33.

Yang Q, Xu Z, Zheng L, Zhang L, You Q, Sun J (2018) Multimodal detection of PD-L1: reasonable biomarkers for immune checkpoint inhibitor. Am J Cancer Res 8(9):1689–1696PubMedPubMedCentral

34.

Xu Y, Wan B, Chen X, Zhan P, Zhao Y, Zhang T, Liu H, Afzal MZ, Dermime S, Hochwald SN, Hofman P, Borghaei H, Lin D, Lv T, Song Y (2019) The association of PD-L1 expression with the efficacy of anti-PD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials. Transl Lung Cancer Res 8(4):413–428. https://doi.org/10.21037/tlcr.2019.08.09 CrossRefPubMedPubMedCentral

35.

Enkhbat T, Nishi M, Takasu C, Yoshikawa K, Jun H, Tokunaga T, Kashihara H, Ishikawa D, Shimada M (2018) Programmed cell death ligand 1 expression is an independent prognostic factor in colorectal cancer. Anticancer Res 38(6):3367–3373. https://doi.org/10.21873/anticanres.12603 CrossRefPubMed

36.

Zhou C, Che G, Zheng X, Qiu J, Xie Z, Cong Y, Pei X, Zhang H, Sun H, Ma H (2019) Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer. J Cancer Res Clin Oncol. https://doi.org/10.1007/s00432-019-03025-8 CrossRefPubMed

37.

Shan T, Chen S, Wu T, Yang Y, Li S, Chen X (2019) PD-L1 expression in colon cancer and its relationship with clinical prognosis. Int J Clin Exp Pathol 12(5):1764–1769PubMedPubMedCentral

38.

Zippelius A, Schreiner J, Herzig P, Muller P (2015) Induced PD-L1 expression mediates acquired resistance to agonistic anti-CD40 treatment. Cancer Immunol Res 3(3):236–244. https://doi.org/10.1158/2326-6066.cir-14-0226 CrossRefPubMed

39.

Christofi T, Baritaki S, Falzone L, Libra M, Zaravinos A (2019) Current perspectives in cancer immunotherapy. Cancers (Basel). https://doi.org/10.3390/cancers11101472 CrossRef

40.

Berntsson J, Eberhard J, Nodin B, Leandersson K, Larsson AH, Jirstrom K (2018) Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: relationship with sidedness and prognosis. Oncoimmunology 7(8):e1465165. https://doi.org/10.1080/2162402x.2018.1465165 CrossRefPubMedPubMedCentral

Titel: The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study
verfasst von: Jinsong Su
Baiyun Dai
Weitang Yuan
Guixian Wang
Zhiyong Zhang
Zhen Li
Jinbo Liu
Junmin Song
Publikationsdatum: 20.04.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04069-1

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

The influence of PD-L1 genetic variation on the prognosis of R0 resection colorectal cancer patients received capecitabine-based adjuvant chemotherapy: a long-term follow-up, real-world retrospective study