Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.,Expert Review of Molecular Diagnostics

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Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.
Expert Review of Molecular Diagnostics ( IF 3.9 ) Pub Date : 2020-07-13 , DOI: 10.1080/14737159.2020.1784728
Mutlu Dogan ₁ , Servet Guresci ₂ , Yusuf Acikgoz ₃ , Yakup Ergun ₃ , Fahriye Tugba Kos ₄ , Onder Bozdogan ₅ , Oznur Bal ₃

Affiliation

Background

We aimed to evaluate the correlation between MKK4 expression and clinicopathological features, KRAS/NRAS mutation in colorectal cancer.

Methods

MKK4 expression was assessed by immunoreactivity score (IRS). Staining intensity(SI) and percentage of positively stained cells (PP) were used for IRS (IRS = SI×PP). Cutoffs were explored with ROC analysis. Patients were grouped as WIR (‘weak immunoreactive’; IRS:0–2) and SIR (‘strong immunoreactive’; IRS: >3).

Results

We enrolled 95 patients. 63.2% had metastasis. Median follow-up was 31.4 months. KRAS/NRAS mutation rate was 45.2%. Median values for OS, DFS, and PFS were as 31.6, 17.2, and 10.3 months. WIR group had longer OS (p = 0.03). Recurrence rate was 36.8%. Median DFS was longer for recurrent patients in WIR group (p = 0.055). KRAS or NRAS wild-type patients and those with left-sided tumors in WIR group had longer OS (p = 0.029, p = 0.024, p = 0.03). There was no PFS difference (p: 0.15). In correlation analysis, there was a negative correlation between MKK4 expression and KRAS mutation, NRAS mutation, OS, PFS, DFS (r: –0,06; r: –0,02; r: –0,10; r: –0,06; r: –0,34). Only the correlation for MKK4 expression and DFS was significant (p = 0.04).

Conclusion

MKK4 expression inversely correlates with survival outcomes. Patients with KRAS/NRAS wild-type, left-sided tumors with WIR had longer OS.

中文翻译：

MKK4（丝裂原活化蛋白激酶激酶 4）表达、临床病理特征和 KRAS/NRAS 突变在结直肠癌中是否存在相关性。

背景

我们旨在评估 MKK4 表达与临床病理特征、结直肠癌 KRAS/NRAS 突变之间的相关性。

方法

通过免疫反应性评分 (IRS) 评估 MKK4 表达。染色强度（SI）和阳性染色细胞的百分比（PP）用于 IRS（IRS = SI×PP）。使用 ROC 分析探索临界值。患者分为 WIR（“弱免疫反应”；IRS：0-2）和 SIR（“强免疫反应”；IRS：>3）。

结果

我们招募了 95 名患者。63.2%有转移。中位随访时间为 31.4 个月。KRAS/NRAS 突变率为 45.2%。OS、DFS 和 PFS 的中位数分别为 31.6、17.2 和 10.3 个月。WIR 组的 OS 更长（p = 0.03）。复发率为36.8%。WIR 组复发患者的中位 DFS 更长（p = 0.055）。KRAS 或 NRAS 野生型患者和 WIR 组左侧肿瘤患者的 OS 更长（p = 0.029，p = 0.024，p = 0.03）。没有 PFS 差异（p：0.15）。在相关分析中，MKK4表达与KRAS突变、NRAS突变、OS、PFS、DFS呈负相关（r：–0,06；r：–0,02；r : –0,10; r : –0,06; r : –0,34)。只有 MKK4 表达和 DFS 的相关性是显着的（p = 0.04）。