Early low blood MALT1 expression levels forecast better efficacy of PD‑1 inhibitor‑based treatment in patients with metastatic colorectal cancer

Abstract

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates colorectal cancer (CRC) malignant behaviors and tumor immune escape. The present study aimed to explore the association of MALT1 with treatment response and survival time among patients with metastatic CRC (mCRC) after programmed cell death protein-1 (PD-1) inhibitor-based treatment. MALT1 from the blood samples of 75 patients with unresectable mCRC receiving PD-1 inhibitor-based treatment at baseline and after 2-cycle treatment, as well as 20 healthy controls (HCs), was detected by reverse transcription-quantitative PCR. In the patients with mCRC, the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were calculated. MALT1 expression was elevated in patients with mCRC compared with that in HCs (P<0.001). In patients with mCRC, MALT1 expression was positively correlated with multiple (vs. single) metastasis (P=0.032) and peritoneum metastasis (P=0.029). MALT1 levels before treatment were decreased in ORR patients vs. non-ORR patients (P=0.043) and in DCR patients vs. non-DCR patients (P=0.007). Additionally, MALT1 expression was reduced after treatment compared with that before treatment (P<0.001). Meanwhile, MALT1 expression after treatment was notably decreased in ORR patients vs. non-ORR patients (P<0.001) and in DCR patients vs. non-DCR patients (P<0.001). Furthermore, a low MALT1 level before treatment was associated with longer PFS (P=0.030) and OS (P=0.025) times. Decreased MALT1 expression after treatment and a decline in MALT1 expression of >30% after treatment (ratio to MALT1 before treatment) (both P≤0.001) presented more significant associations with prolonged PFS and OS times. In conclusion, early low levels of blood MALT1 during therapy may predict an improved response to PD-1 inhibitor-based treatment and survival time in patients with mCRC.

Keywords: MALT1; PD-1 inhibitor; mCRC; survival; treatment response.

Figure 1.

MALT1 is elevated in patients with mCRC vs. HCs. (A) Comparison of MALT1 expression level in patients with mCRC vs. HCs. The numbers above the bars represent the median (confidence interval). (B) The capability of MALT1 to discriminate patients with mCRC from HCs. AUC, area under curve; CI, confidence interval; HCs, healthy controls; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; mCRC, metastatic colorectal cancer.

Figure 2.

MALT1 expression levels before treatment are decreased in response vs. non-response patients withmCRC. (A) Treatment response of patients. The numbers above the bars represent the number of patients (%). (B) Comparison of MALT1 expression level before treatment in ORR patients vs. non-ORR patients, and in (C) DCR patients vs. non-DCR patients. The numbers above the bars in (B) and (C) represent the median (confidence interval). CR, complete response; DCR, disease control rate; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.

Figure 3.

MALT1 expression decreases after treatment in patients with mCRC. Comparison of MALT1 expression level before treatment vs. after treatment in (A) all patients, (B) ORR patients, (C) non-ORR patients, (D) DCR patients (E) and non-DCR patients. (F) Comparison of MALT1 expression level after treatment in ORR patients vs. non-ORR patients, and in (G) DCR patients vs. non-DCR patients. The numbers above the bars in (F) and (G) represent the median (confidence interval). DCR, disease control rate; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; ORR, objective response rate.

Figure 4.

Low MALT1 expression is associated with prolonged survival times in patients with mCRC. Association of low MALT1 expression before treatment with (A) PFS and (B) OS times. Association of low MALT1 expression after treatment with (C) PFS and (D) OS times. Association of a MALT1 expression level decline of >30% with (E) PFS and (F) OS times. MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; OS, overall survival; PFS, progression-free survival.